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Wiley - Encyclopedia of Medical Devices and Instrumentation - Vol. 6
Wiley - Encyclopedia of Medical Devices and Instrumentation - Vol. 6
Wiley - Encyclopedia of Medical Devices and Instrumentation - Vol. 6
Edward S. Sternick
TuftsNew England Medical Center
Editorial Staff
Vice President, STM Books: Janet Bailey
Associate Publisher: George J. Telecki
Editorial Director: Sean Pidgeon
Director, Book Production and Manufacturing:
Camille P. Carter
Production Manager: Shirley Thomas
Illustration Manager: Dean Gonzalez
Senior Production Editor: Kellsee Chu
Editorial Program Coordinator: Surlan Murrell
ENCYCLOPEDIA OF
John G. Webster
University of WisconsinMadison
Copyright # 2006 by John Wiley & Sons, Inc. All rights reserved.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey
Published simultaneously in Canada
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CONTRIBUTOR LIST
ABDEL HADY, MAZEN, McMaster University, Hamilton,
Ontario Canada, Bladder Dysfunction, Neurostimulation
of
ABEL, L.A., University of Melbourne, Melbourne, Australia,
Ocular Motility Recording and Nystagmus
ABREU, BEATRIZ C., Transitional Learning Center at Galveston, Galveston, Texas, Rehabilitation, Computers in
Cognitive
ALEXANDER, A.L., University of WisconsinMadison, Madison, Wisconsin, Magnetic Resonance Imaging
ALI, ABBAS, University of Illinois, at Urbana-Champaign,
Bioinformatics
ALI, MUFTU, School of Dental Medicine, Boston, Massachusetts, Tooth and Jaw, Biomechanics of
ALPERIN, NOAM, University of Illinois at Chicago, Chicago,
Illinois, Hydrocephalus, Tools for Diagnosis and Treatment of
ANSON, DENIS, College Misericordia, Dallas, Pennsylvania,
Environmental Control
ARENA, JOHN C., VA Medical Center and Medical College of
Georgia, Biofeedback
ARIEL, GIDEON, Ariel Dynamics, Canyon, California, Biomechanics of Exercise Fitness
ARMSTRONG, STEVE, University of Iowa, Iowa City, Iowa,
Biomaterials for Dentistry
ASPDEN, R.M., University of Aberdeen, Aberdeen, United
Kingdom, Ligament and Tendon, Properties of
AUBIN, C.E., Polytechniquie Montreal, Montreal Quebec,
Canada, Scoliosis, Biomechanics of
AYRES, VIRGINIA M., Michigan State University, East Lansing, Michigan, Microscopy, Scanning Tunneling
AZANGWE, G., Ligament and Tendon, Properties of
BACK, LLOYD H., California Institute of Technology, Pasadena, California, Coronary Angioplasty and Guidewire
Diagnostics
BADYLAK, STEPHEN F., McGowan Institute for Regenerative
Medicine, Pittsburgh, Pennsylvania, Sterilization of Biologic Scaffold Materials
BANDYOPADHYAY, AMIT, Washington State University, Pullman, Washington, Orthopedic Devices, Materials and
Design for
BANERJEE, RUPAK K., University of Cincinnati, Cincinnati,
Ohio, Coronary Angioplasty and Guidewire Diagnostics
BARBOUR, RANDALL L., State University of New York Downstate Medical Center, Brooklyn, New York, Peripheral
Vascular Noninvasive Measurements
BARKER, STEVEN J., University of Arizona, Tucson, Arizona,
Oxygen Monitoring
BARTH, ROLF F., The Ohio State University, Columbus,
Ohio, Boron Neutron Capture Therapy
BECCHETTI, F.D., University of Michigan, Ann Arbor, Michigan, Radiotherapy, Heavy Ion
BELFORTE, GUIDO, Politecnico di Torino Department of
Mechanics, Laryngeal Prosthetic Devices
BENKESER, PAUL, Georgia Institute of Technology, Atlanta,
Georgia, Biomedical Engineering Education
BENNETT, JAMES R., University of Iowa, Iowa City, Iowa,
Digital Angiography
vi
CONTRIBUTOR LIST
CONTRIBUTOR LIST
vii
viii
CONTRIBUTOR LIST
CONTRIBUTOR LIST
LEI, XING, Stanford University, Stanford, California, Radiation Dose Planning, Computer-Aided
LEWIS, MATTHEW C., Medical College of Wisconsin, Milwaukee, Wisconsin, Hyperbaric Oxygenation
LI, CHAODI, University of Notre Dame, Notre Dame, Indiana,
Bone Cement, Acrylic
LI, JONATHAN G., University of Florida, Gainesville, Florida,
Radiation Dose Planning, Computer-Aided
LI, QIAO, University of Michigan, Ann Arbor, Michigan,
Immunotherapy
LI, YANBIN, University of Arkansas, Fayetteville, Arkansas,
Piezoelectric Sensors
LIBOFF, A.R., Oakland University, Rochester, Michigan,
Bone Ununited Fracture and Spinal Fusion, Electrical
Treatment of
LIGAS, JAMES, University of Connecticut, Farmington, Connecticut, Respiratory Mechanics and Gas Exchange
LIMOGE, AIME, The Rene Descartes University of Paris, Paris,
France, Electroanalgesia, Systemic
LIN, PEI-JAN PAUL, Beth Israel Deaconess Medical Center,
Boston, Massachusets, Mammography
LIN, ZHIYUE, University of Kansas Medical Center, Kansas
City, Kansas, Electrogastrogram
LINEAWEAVER, WILLIAM C., Unive rsity of Mississippi Medical Center, Jackson, Mississippi, Hyperbaric Medicine
LIPPING, TARMO, Tampere University of Technology, Pori,
Finland, Monitoring in Anesthesia
LIU, XIAOHUA, The University of Michigan, Ann Arbor,
Michigan, Polymeric Materials
LLOYD, J.J., Regional Medical Physics Department, Newcastle-upon-Tyne, United Kingdom, Ultraviolet Radiation
in Medicine
LOEB, ROBERT, University of Arizona, Tuscon, Arizona,
Anesthesia Machines
LOPES DE MELO, PEDRO, State University of Rio de Janeiro,
Terreo Salas, Maracana, Thermistors
LOUDON, ROBERT G., Lung Sounds
LOW, DANIEL A., Washington University School of Medicine,
St. Louis, Missouri, Radiation Therapy Simulator
LU, LICHUN, Mayo Clinic, College of Medicine, Rochester,
Minnesota, Microscopy, Electron
LU, ZHENG FENG, Columbia University, New York, New
York, Screen-Film Systems
LYON, ANDREW W., University of Calgary, Calgary, Canada,
Flame Atomic Emission Spectrometry and Atomic
Absorption Spectrometry
LYON, MARTHA E., University of Calgary, Calgary, Canada,
Flame Atomic Emission Spectrometry and Atomic
Absorption Spectrometry
MA, C-M CHARLIE, Fox Chase Cancer Center, Philadelphia,
Pennsylvania, X-Ray Therapy Equipment, Low and Medium Energy
MACIA, NARCISO F., Arizona State University at the Polytechnic Campus, Mesa, Arizona, Pneumotachometers
MACKENZIE, COLIN F., University of Maryland, School of
Medicine, Shock, Treatment of
MACKIE, THOMAS R., University of Wisconsin, Madison,
Wisconsin, Tomotherapy
MADNANI, ANJU, LSU Medical Centre, Shreveport, Louisiana, Transcutaneous Electrical Nerve Stimulation
(TENS)
MADNANI, SANJAY, LSU Medical Centre, Shreveport, Louisiana, Transcutaneous Electrical Nerve Stimulation
(TENS)
ix
CONTRIBUTOR LIST
CONTRIBUTOR LIST
xi
xii
CONTRIBUTOR LIST
TRAUTMAN, EDWIN D., RMF Strategies, Cambridge, Massachusetts, Cardiac Output, Thermodilution Measurement
of
TREENA, LIVINGSTON ARINZEH, New Jersey Institute of Technology, Newark, New Jersey, Polymeric Materials
TRENTMAN, TERRENCE L., Mayo Clinic Scottsdale, Spinal
Cord Stimulation
TROKEN, ALEXANDER J., University of Illinois at Chicago,
Chicago, Illinois, Cartilage and Meniscus, Properties of
TSAFTARIS, SOTIRIOS A., Northwestern University, Evanston,
Illinois, DNA Sequence
TSOUKALAS, D., NTUA, Athens, Attiki, Greece, Capacitive
Microsensors for Biomedical Applications
TULIPAN, NOEL, Vanderbilt University Medical Center,
Nashville, Tennessee, Intrauterine Surgical Techniques
TUTEJA, ASHOK K., University of Utah, Salt Lake City, Utah,
Anorectal Manometry
TY, SMITH N., University of California, San Diego, California, Physiological Systems Modeling
TYRER, HARRY W., University of Missouri-Columbia, Columbia, Missouri, Cytology, Automated
VALVANO, JONATHAN W., The University of Texas, Austin,
Texas, Bioheat Transfer
VAN DEN HEUVAL, FRANK, Wayne State University, Detroit,
Michigan, Imaging Devices
VEIT, SCHNABEL, Aalborg University, Aalborg, Denmark,
Electroneurography
VELANOVICH, VIC, Henry Ford Hospital, Detroit, Michigan,
Esophageal Manometry
VENKATASUBRAMANIAN,
GANAPRIYA,
Arizona
State
University, Tempe, Arizona, Functional Electrical
Stimulation
VERAART, CLAUDE, Catholique University of Louvain, Brussels, Belgium, Visual Prostheses
VERDONCK, PASCAL, Ghent University, Belgium, Hemodynamics
VERMARIEN, HERMAN, Vrije Universiteit Brussel, Brussels,
Belgium, Phonocardiography, Recorders, Graphic
VEVES, ARISTIDIS, Harvard Medical School, Boston, Massachusetts, Cutaneous Blood Flow, Doppler Measurement
of
VICINI, PAOLO, University of Washington, Seattle, Washington, Pharmacokinetics and Pharmacodynamics
VILLE, JA NTTI, Tampere University of Technology, Pori,
Finland, Monitoring in Anesthesia
VRBA, JINI, VSM MedTech Ltd., Biomagnetism
WAGNER, THOMAS, H., M. D. Anderson Cancer Center
Orlando, Orlando, Florida, Radiosurgery, Stereotactic
WAHLEN, GEORGE E., Veterans Affairs Medical Center and
the University of Utah, Salt Lake City, Utah, Anorectal
Manometry
WALKER, GLENN M., North Carolina State University,
Raleigh, North Carolina, Microfluidics
WALTERSPACHER, DIRK, The Johns Hopkins University, Baltimore, Maryland, Electroencephalography
WAN, LEO Q., Liu Ping, Columbia University, New York,
New York, Cartilage and Meniscus, Properties of
WANG, GE, University of Iowa, Iowa City, Iowa, Computed
Tomography Simulators
WANG, HAIBO, Louisiana State University Health Center
Shreveport, Louisiana, Monitoring, Umbilical Artery
and Vein, Ambulatory Monitoring
WANG, HONG, Wayne State University, Detroit, Michigan,
Anesthesia, Computers in
CONTRIBUTOR LIST
xiii
PREFACE
The Encyclopedia of Medical Devices and Instrumentation is excellent for browsing and searching for those new
divergent associations that may advance work in a peripheral field. While it can be used as a reference for facts, the
articles are long enough that they can serve as an educational instrument and provide genuine understanding of a
subject.
One can use this work just as one would use a dictionary,
since the articles are arranged alphabetically by topic. Cross
references assist the reader looking for subjects listed under
slightly different names. The index at the end leads the
reader to all articles containing pertinent information on
any subject. Listed on pages xxi to xxx are all the abbreviations and acronyms used in the Encyclopedia. Because of
the increasing use of SI units in all branches of science, these
units are provided throughout the Encyclopedia articles as
well as on pages xxxi to xxxv in the section on conversion
factors and unit symbols.
I owe a great debt to the many people who have contributed to the creation of this work. At John Wiley & Sons,
Encyclopedia Editor George Telecki provided the idea and
guiding influence to launch the project. Sean Pidgeon was
Editorial Director of the project. Assistant Editors Roseann
Zappia, Sarah Harrington, and Surlan Murrell handled the
myriad details of communication between publisher, editor,
authors, and reviewers and stimulated authors and
reviewers to meet necessary deadlines.
My own background has been in the electrical aspects of
biomedical engineering. I was delighted to have the assistance of the editorial board to develop a comprehensive
encyclopedia. David J. Beebe suggested cellular topics such
as microfluidics. Jerry M. Calkins assisted in defining the
chemically related subjects, such as anesthesiology.
Michael R. Neuman suggested subjects related to sensors,
such as in his own workneonatology. Joon B. Park has
written extensively on biomaterials and suggested related
subjects. Edward S. Sternick provided many suggestions
from medical physics. The Editorial Board was instrumental both in defining the list of subjects and in suggesting
authors.
This second edition brings the field up to date. It is
available on the web at http://www.mrw.interscience.wiley.
com/emdi, where articles can be searched simultaneously to
provide rapid and comprehensive information on all aspects
of medical devices and instrumentation.
This six-volume work is an alphabetically organized compilation of almost 300 articles that describe critical aspects of
medical devices and instrumentation.
It is comprehensive. The articles emphasize the contributions of engineering, physics, and computers to each of the
general areas of anesthesiology, biomaterials, burns, cardiology, clinical chemistry, clinical engineering, communicative disorders, computers in medicine, critical care
medicine, dermatology, dentistry, ear, nose, and throat,
emergency medicine, endocrinology, gastroenterology,
genetics, geriatrics, gynecology, hematology, heptology,
internal medicine, medical physics, microbiology, nephrology, neurology, nutrition, obstetrics, oncology, ophthalmology, orthopedics, pain, pediatrics, peripheral vascular
disease, pharmacology, physical therapy, psychiatry, pulmonary medicine, radiology, rehabilitation, surgery, tissue
engineering, transducers, and urology.
The discipline is defined through the synthesis of the core
knowledge from all the fields encompassed by the application of engineering, physics, and computers to problems in
medicine. The articles focus not only on what is now useful
but also on what is likely to be useful in future medical
applications.
These volumes answer the question, What are the
branches of medicine and how does technology assist each
of them? rather than What are the branches of technology
and how could each be used in medicine? To keep this work
to a manageable length, the practice of medicine that is
unassisted by devices, such as the use of drugs to treat
disease, has been excluded.
The articles are accessible to the user; each benefits from
brevity of condensation instead of what could easily have
been a book-length work. The articles are designed not for
peers, but rather for workers from related fields who wish to
take a first look at what is important in the subject.
The articles are readable. They do not presume a detailed
background in the subject, but are designed for any person
with a scientific background and an interest in technology.
Rather than attempting to teach the basics of physiology or
Ohms law, the articles build on such basic concepts to show
how the worlds of life science and physical science meld to
produce improved systems. While the ideal reader might be
a person with a Masters degree in biomedical engineering or
medical physics or an M.D. with a physical science undergraduate degree, much of the material will be of value to
others with an interest in this growing field. High school
students and hospital patients can skip over more technical
areas and still gain much from the descriptive presentations.
JOHN G. WEBSTER
University of Wisconsin, Madison
xv
LIST OF ARTICLES
CARDIAC OUTPUT, FICK TECHNIQUE FOR
CARDIAC OUTPUT, INDICATOR DILUTION
MEASUREMENT OF
CARDIAC OUTPUT, THERMODILUTION
MEASUREMENT OF
CARDIOPULMONARY RESUSCITATION
CARTILAGE AND MENISCUS, PROPERTIES OF
CELL COUNTERS, BLOOD
CELLULAR IMAGING
CHROMATOGRAPHY
CO2 ELECTRODES
COBALT 60 UNITS FOR RADIOTHERAPY
COCHLEAR PROSTHESES
CODES AND REGULATIONS: MEDICAL DEVICES
CODES AND REGULATIONS: RADIATION
COLORIMETRY
COLPOSCOPY
COMMUNICATION DEVICES
COMMUNICATIVE DISORDERS, COMPUTER
APPLICATIONS FOR
COMPUTED TOMOGRAPHY
COMPUTED TOMOGRAPHY SCREENING
COMPUTED TOMOGRAPHY SIMULATORS
COMPUTED TOMOGRAPHY, SINGLE PHOTON
EMISSION
COMPUTER-ASSISTED DETECTION AND DIAGNOSIS
COMPUTERS IN THE BIOMEDICAL LABORATORY
CONTACT LENSES
CONTINUOUS POSITIVE AIRWAY PRESSURE
CONTRACEPTIVE DEVICES
CORONARY ANGIOPLASTY AND GUIDEWIRE
DIAGNOSTICS
CRYOSURGERY
CUTANEOUS BLOOD FLOW, DOPPLER
MEASUREMENT OF
CYSTIC FIBROSIS SWEAT TEST
CYTOLOGY, AUTOMATED
DEFIBRILLATORS
DIFFERENTIAL COUNTS, AUTOMATED
DIGITAL ANGIOGRAPHY
DNA SEQUENCE
DRUG DELIVERY SYSTEMS
DRUG INFUSION SYSTEMS
ECHOCARDIOGRAPHY AND DOPPLER
ECHOCARDIOGRAPHY
ELECTROANALGESIA, SYSTEMIC
ELECTROCARDIOGRAPHY, COMPUTERS IN
ELECTROCONVULSIVE THERAPY
ELECTROENCEPHALOGRAPHY
ELECTROGASTROGRAM
ELECTROMYOGRAPHY
ELECTRONEUROGRAPHY
ELECTROPHORESIS
xviii
LIST OF ARTICLES
ELECTROPHYSIOLOGY
ELECTRORETINOGRAPHY
ELECTROSURGICAL UNIT (ESU)
ENDOSCOPES
ENGINEERED TISSUE
ENVIRONMENTAL CONTROL
EQUIPMENT ACQUISITION
EQUIPMENT MAINTENANCE, BIOMEDICAL
ESOPHAGEAL MANOMETRY
EVOKED POTENTIALS
EXERCISE STRESS TESTING
EYE MOVEMENT, MEASUREMENT TECHNIQUES FOR
FETAL MONITORING
FIBER OPTICS IN MEDICINE
FLAME ATOMIC EMISSION SPECTROMETRY AND
ATOMIC ABSORPTION SPECTROMETRY
FLOWMETERS
FLUORESCENCE MEASUREMENTS
FUNCTIONAL ELECTRICAL STIMULATION
GAMMA KNIFE
GAS AND VACUUM SYSTEMS, CENTRALLY PIPED
MEDICAL
GASTROINTESTINAL HEMORRHAGE
GLUCOSE SENSORS
HEART VALVE PROSTHESES
HEART VALVE PROSTHESES, IN VITRO FLOW
DYNAMICS OF
HEART VALVES, PROSTHETIC
HEART, ARTIFICIAL
HEARTLUNG MACHINES
HEAT AND COLD, THERAPEUTIC
HEMODYNAMICS
HIGH FREQUENCY VENTILATION
HIP JOINTS, ARTIFICIAL
HOME HEALTH CARE DEVICES
HUMAN FACTORS IN MEDICAL DEVICES
HUMAN SPINE, BIOMECHANICS OF
HYDROCEPHALUS, TOOLS FOR DIAGNOSIS
AND TREATMENT OF
HYPERBARIC MEDICINE
HYPERBARIC OXYGENATION
HYPERTHERMIA, INTERSTITIAL
HYPERTHERMIA, SYSTEMIC
HYPERTHERMIA, ULTRASONIC
IMAGE INTENSIFIERS AND FLUOROSCOPY
IMAGING DEVICES
IMMUNOLOGICALLY SENSITIVE FIELD-EFFECT
TRANSISTORS
IMMUNOTHERAPY
IMPEDANCE PLETHYSMOGRAPHY
IMPEDANCE SPECTROSCOPY
INCUBATORS, INFANT
INTEGRATED CIRCUIT TEMPERATURE SENSOR
INTRAAORTIC BALLOON PUMP
INTRAUTERINE SURGICAL TECHNIQUES
IONIZING RADIATION, BIOLOGICAL EFFECTS OF
ION-SENSITIVE FIELD-EFFECT TRANSISTORS
JOINTS, BIOMECHANICS OF
LARYNGEAL PROSTHETIC DEVICES
LENSES, INTRAOCULAR
LIGAMENT AND TENDON, PROPERTIES OF
LIST OF ARTICLES
xix
SEXUAL INSTRUMENTATION
SHOCK, TREATMENT OF
SKIN SUBSTITUTE FOR BURNS, BIOACTIVE
SKIN TISSUE ENGINEERING FOR REGENERATION
SKIN, BIOMECHANICS OF
SLEEP LABORATORY
SLEEP STUDIES, COMPUTER ANALYSIS OF
SPINAL CORD STIMULATION
SPINAL IMPLANTS
STATISTICAL METHODS
STEREOTACTIC SURGERY
STERILIZATION OF BIOLOGIC SCAFFOLD
MATERIALS
STRAIN GAGES
TACTILE STIMULATION
TELERADIOLOGY
TEMPERATURE MONITORING
THERMISTORS
THERMOCOUPLES
THERMOGRAPHY
THERMOMETRY
TISSUE ABLATION
TISSUE ENGINEERING
TOMOTHERAPY
TONOMETRY, ARTERIAL
TOOTH AND JAW, BIOMECHANICS OF
TRACER KINETICS
TRANSCUTANEOUS ELECTRICAL NERVE
STIMULATION (TENS)
ULTRASONIC IMAGING
ULTRAVIOLET RADIATION IN MEDICINE
VASCULAR GRAFT PROSTHESIS
VENTILATORS, ACUTE MEDICAL CARE
VENTILATORY MONITORING
VISUAL FIELD TESTING
VISUAL PROSTHESES
X-RAY EQUIPMENT DESIGN
X-RAY QUALITY CONTROL PROGRAM
X-RAY THERAPY EQUIPMENT, LOW AND
MEDIUM ENERGY
X-RAYS: INTERACTION WITH MATTER
X-RAYS, PRODUCTION OF
ALS
ALT
ALU
AM
AMA
amu
ANOVA
ANSI
AP
APD
APL
APR
AR
Ara-C
ARD
ARDS
ARGUS
ARMA
ARMAX
AS
ASA
ASCII
ASD
ASHE
ASTM
AT
ATA
ATLS
ATN
ATP
ATPD
ATPS
ATR
AUC
AUMC
AV
AZT
BA
BAEP
BAPN
BAS
BASO
BB
BBT
xxi
xxii
BCC
BCD
BCG
BCLS
BCRU
BDI
BE
BET
BH
BI
BIH
BIPM
BJT
BMDP
BME
BMET
BMO
BMR
BOL
BP
BR
BRM
BRS
BSS
BTG
BTPS
BUN
BW
CA
CABG
CAD/CAM
CAD/D
CADD
CAI
CAM
cAMP
CAPD
CAPP
CAT
CATS
CAVH
CB
CBC
CBF
CBM
CBV
CC
CCC
CCD
CCE
CCF
CCL
CCM
CCPD
Body-centered cubic
Binary-coded decimal
Ballistocardiogram
Basic cardiac life support
British Commitee on Radiation Units
and Measurements
Beck depression inventory
Base excess; Binding energy
Brunauer, Emmett, and Teller methods
His bundle
Biological indicators
Beth Israel Hospital
International Bureau of Weights and
Measurements
Bipolar junction transistor
Biomedical Programs
Biomedical engineering
Biomedical equipment technician
Biomechanically optimized
Basal metabolic rate
Beginning of life
Bereitschafts potential; Break point
Polybutadiene
Biological response modifier
Bibliographic retrieval services
Balanced salt solution
Beta thromboglobulin
Body temperature pressure saturated
Blood urea nitrogen
Body weight
Conductive adhesives
Coronary artery by-pass grafting
Computer-aided design/computer-aided
manufacturing
Computer-aided drafting and design
Central axis depth dose
Computer assisted instruction;
Computer-aided instruction
Computer-assisted management
Cyclic AMP
Continuous ambulatory peritoneal
dialysis
Child amputee prosthetic project
Computerized axial tomography
Computer-assisted teaching system;
Computerized aphasia treatment system
Continuous arteriovenous hemofiltration
Conjugated bilirubin; Coulomb barrier
Complete blood count
Cerebral blood flow
Computer-based management
Cerebral blood volume
Closing capacity
Computer Curriculum Company
Charge-coupled device
Capacitance contact electrode
Cross-correlation function
Cardiac catheterization laboratory
Critical care medical services
Continuous cycling peritoneal
dialysis
CCTV
CCU
CD
CDR
CDRH
CEA
CF
CFC
CFR
CFU
CGA
CGPM
CHO
CHO
CI
CICU
CIF
CIN
CK
CLAV
CLSA
CM
CMAD
CMI
CMRR
CMV
CNS
CNV
CO
COBAS
COPD
COR
CP
CPB
CPET
CPM
CPP
CPR
cps
CPU
CR
CRBB
CRD
CRL
CRT
CS
CSA
CSF
CSI
CSM
CT
CTI
CV
C.V.
CVA
CVP
CVR
CW
CWE
CWRU
DAC
DAS
dB
DB
DBMS
DBS
dc
DCCT
DCP
DCS
DDC
DDS
DE
DEN
DERS
DES
d.f.
DHCP
DHE
DHEW
DHHS
DHT
DI
DIC
DIS
DL
DLI
DM
DME
DN
DNA
DOF
DOS
DOT-NHTSA
DPB
DPG
DQE
DRESS
DRG
DSA
DSAR
DSB
DSC
D-T
DTA
d.u.
DUR
DVT
EA
EB
EBCDIC
Coefficient of variation
Cerebral vascular accident
Central venous pressure
Cardiovascular resistance
Continuous wave
Coated wire electrodes
Case Western Reserve University
Digital-to-analog converter
Data acquisition system
Decibel
Direct body
Data base management system
Deep brain stimulation
Direct current
Diabetes control and complications trial
Distal cavity pressure
Dorsal column stimulation
Deck decompression chamber
Deep diving system
Dispersive electrode
Device experience network
Drug exception ordering system
Diffuse esophageal spasm
Distribution function
Distributed Hospital Computer Program
Dihematoporphyrin ether
Department of Health Education and
Welfare
Department of Health and Human Services
Duration of hypothermia
Deionized water
Displacement current
Diagnostic interview schedule
Double layer
Difference lumen for intensity
Delta modulation
Dropping mercury electrode
Donation number
Deoxyribonucleic acid
Degree of freedom
Drug ordering system
Department of Transportation Highway
Traffic Safety Administration
Differential pencil beam
Diphosphoglycerate
Detection quantum efficiency
Depth-resolved surface coil spectroscopy
Diagnosis-related group
Digital subtraction angiography
Differential scatter-air ratio
Double strand breaks
Differential scanning calorimetry
Deuterium-on-tritium
Differential thermal analysis
Density unit
Duration
Deep venous thrombosis
Esophageal accelerogram
Electron beam
Extended binary code decimal interchange
code
EBS
EBV
EC
ECC
ECCE
ECD
ECG
ECM
ECMO
ECOD
ECRI
ECS
ECT
EDD
EDP
EDTA
EDX
EEG
EEI
EELV
EER
EF
EF
EFA
EGF
EGG
EIA
EIU
ELF
ELGON
ELISA
ELS
ELV
EM
EMBS
emf
EMG
EMGE
EMI
EMS
EMT
ENT
EO
EOG
EOL
EOS
EP
EPA
ER
ERCP
ERG
ERMF
ERP
ERV
xxiii
xxiv
ESCA
ESI
ESRD
esu
ESU
ESWL
ETO, Eto
ETT
EVA
EVR
EW
FAD
FARA
FBD
FBS
fcc
FCC
Fct
FDA
FDCA
FE
FECG
FEF
FEL
FEM
FEP
FES
FET
FEV
FFD
FFT
FGF
FHR
FIC
FID
FIFO
FITC
FL
FM
FNS
FO
FO-CRT
FP
FPA
FR
FRC
FSD
FTD
FTIR
FTMS
FU
FUDR
FVC
FWHM
FWTM
GABA
GAG
GBE
GC
GDT
GFR
GHb
GI
GLC
GMV
GNP
GPC
GPH
GPH-EW
GPO
GSC
GSR
GSWD
HA
HAM
Hb
HBE
HBO
HC
HCA
HCFA
HCL
hcp
HCP
HDPE
HECS
HEMS
HEPA
HES
HETP
HF
HFCWO
HFER
HFJV
HFO
HFOV
HFPPV
HFV
HHS
HIBC
HIMA
HIP
HIS
HK
HL
HMBA
HMO
HMWPE
HOL
HP
HpD
HPLC
HPNS
HPS
HPX
HR
HRNB
H/S
HSA
HSG
HTCA
HTLV
HU
HVL
HVR
HVT
IA
IABP
IAEA
IAIMS
IASP
IC
ICCE
ICD
ICDA
ICL
ICP
ICPA
ICRP
ICRU
ICU
ID
IDDM
IDE
IDI
I:E
IEC
IEEE
IEP
BETS
IF
IFIP
IFMBE
IGFET
IgG
IgM
IHP
IHSS
II
IIIES
IM
IMFET
IMIA
IMS
IMV
INF
IOL
IPC
IPD
IPG
IPI
IPPB
IPTS
IR
IRB
IRBBB
IRPA
IRRAS
IRRS
IRS
IRV
IS
ISC
ISDA
ISE
ISFET
ISIT
ISO
ISS
IT
ITEP
ITEPI
ITLC
IUD
IV
IVC
IVP
JCAH
JND
JRP
KB
Kerma
KO
KPM
KRPB
LA
LAD
LAE
LAK
LAL
LAN
LAP
LAT
LBBB
LC
xxv
xxvi
LCC
LCD
LDA
LDF
LDH
LDPE
LEBS
LED
LEED
LES
LESP
LET
LF
LH
LHT
LL
LLDPE
LLPC
LLW
LM
LNNB
LOS
LP
LPA
LPC
LPT
LPV
LRP
LS
LSC
LSI
LSV
LTI
LUC
LV
LVAD
LVDT
LVEP
LVET
LVH
LYMPH
MAA
MAC
MAN
MAP
MAST
MBA
MBV
MBX
MCA
MCG
MCI
MCMI
MCT
MCV
MDC
MDI
MDP
MDR
MDS
ME
MED
MEDPAR
MEFV
MEG
MeSH
METS
MF
MFP
MGH
MHV
MI
MIC
MIFR
MINET
MIR
MIS
MIT
MIT/BIH
MMA
MMA
MMECT
MMFR
mm Hg
MMPI
MMSE
MO
MONO
MOSFET
MP
MPD
MR
MRG
MRI
MRS
MRT
MS
MSR
MTBF
MTF
MTTR
MTX
MUA
MUAP
MUAPT
MUMPI
MUMPS
MV
MVO2
MVTR
MVV
MW
NAA
NAD
NADH
NADP
NAF
NARM
NBB
NBD
N-BPC
NBS
NCC
NCCLS
NCRP
NCT
NEEP
NEMA
NEMR
NEQ
NET
NEUT
NFPA
NH
NHE
NHLBI
NIR
NIRS
NK
NMJ
NMOS
NMR
NMS
NPH
NPL
NR
NRC
NRZ
NTC
NTIS
NVT
NYHA
ob/gyn
OCR
OCV
OD
ODC
ODT
ODU
OER
OFD
OHL
OHP
OIH
OPG
OR
OS
OTC
OV
PA
PACS
PAD
PAM
PAN
PAP
PAR
PARFR
PARR
PAS
PASG
PBI
PBL
PBT
PC
PCA
PCG
PCI
PCL
PCR
PCRC
PCS
PCT
PCWP
PD
PDD
PDE
p.d.f.
PDL
PDM
PDMSX
PDS
PE
PEEP
PEFR
PEN
PEP
PEPPER
PET
PEU
PF
PFA
PFC
PFT
PG
xxvii
Ocular pneumoplethysmography
Operating room
Object of known size; Operating system
Over the counter
Offset voltage
Posterioanterior; Pulmonary artery;
Pulse amplitude
Picture archiving and communications
systems
Primary afferent depolarization
Pulse amplitude modulation
Polyacrylonitrile
Pulmonary artery pressure
Photoactivation ratio
Program for Applied Research on
Fertility Regulation
Poetanesthesia recovery room
Photoacoustic spectroscopy
Pneumatic antishock garment
Penile brachial index
Positive beam limitation
Polybutylene terephthalate
Paper chromatography; Personal
computer; Polycarbonate
Patient controlled analgesia; Principal
components factor analysis
Phonocardiogram
Physiological cost index
Polycaprolactone; Posterior chamber
lens
Percent regurgitation
Perinatal Clinical Research Center
Patient care system
Porphyria cutanea tarda
Pulmonary capillary wedge pressure
Peritoneal dialysis; Poly-p-dioxanone;
Potential difference; Proportional and
derivative
Percent depth dose; Perinatal Data
Directory
Pregelled disposable electrodes
Probability density function
Periodontal ligament
Pulse duration modulation
Polydimethyl siloxane
Polydioxanone
Polyethylene
Positive end-expiratory pressure
Peak expiratory now rate
Parenteral and enteral nutrition
Preejection period
Programs examine phonetic find
phonological evaluation records
Polyethylene terephthalate;
Positron-emission tomography
Polyetherurethane
Platelet factor
Phosphonoformic add
Petrofluorochemical
Pulmonary function testing
Polyglycolide; Propylene glycol
xxviii
PGA
PHA
PHEMA
PI
PID
PIP
PL
PLA
PLATO
PLD
PLED
PLT
PM
PMA
p.m.f.
PMMA
PMOS
PMP
PMT
PO
Po2
POBT
POM
POMC
POPRAS
PP
PPA
PPF
PPM
PPSFH
PR
PRBS
PRP
PRO
PROM
PS
PSA
PSF
PSI
PSP
PSR
PSS
PT
PTB
PTC
PTCA
PTFE
PTT
PUL
Polyglycolic add
Phytohemagglutinin; Pulse-height
analyzer
Poly-2-hydroxyethyl methacrylate
Propidium iodide
Pelvic inflammatory disease;
Proportional/integral/derivative
Peak inspiratory pressure
Posterior leaflet
Polylactic acid
Program Logic for Automated Teaching
Operations
Potentially lethal damage
Periodic latoralized epileptiform discharge
Platelet
Papillary muscles; Preventive
maintenance
Polymethyl acrylate
Probability mass function
Polymethyl methacrylate
P-type metal oxide silicon
Patient management problem;
Poly(4-methylpentane)
Photomultiplier tube
Per os
Partial pressure of oxygen
Polyoxybutylene terephthalate
Polyoxymethylene
Patient order management and
communication system
Problem Oriented Perinatal Risk
Assessment System
Perfusion pressure; Polyproplyene;
Postprandial (after meals)
Phonemic process analysis
Plasma protein fraction
Pulse position modulation
Polymerized phyridoxalated stroma-free
hemoglobin
Pattern recognition; Pulse rate
Pseudo-random binary signals
Pulse repetition frequency
Professional review organization
Programmable read only memory
Polystyrene
Pressure-sensitive adhesive
Point spread function
Primary skin irritation
Postsynaptic potential
Proton spin resonance
Progressive systemic sclerosis
Plasma thromboplastin
Patellar tendon bearing orthosis
Plasma thromboplastin component;
Positive temperature coefficient;
Pressurized personal transfer capsule
Percutaneous transluminal coronary
angioplasty
Polytetrafluoroethylene
Partial thromboplastin time
Percutaneous ultrasonic lithotripsy
PURA
PUVA
P/V
PVC
PVI
PW
PWM
PXE
QA
QC
R-BPC
R/S
RA
RAD
RAE
RAM
RAP
RAT
RB
RBBB
RBC
RBE
RBF
RBI
RCBD
rCBF
RCC
RCE
R&D
r.e.
RE
REM
REMATE
RES
RESNA
RF
RFI
RFP
RFQ
RH
RHE
RIA
RM
RMR
RMS
RN
RNCA
ROI
ROM
RP
RPA
RPP
RPT
RPV
RQ
RR
RRT
RT
RTD
RTT
r.v.
RV
RVH
RVOT
RZ
SA
SACH
SAD
SAINT
SAL
SALT
SAMI
SAP
SAR
SARA
SBE
SBR
SC
SCAP
SCE
SCI
SCRAD
SCS
SCUBA
SD
SDA
SDS
S&E
SE
SEC
SEM
SEP
SEXAFS
SF
SFD
SFH
SFTR
SG
SGF
SGG
SGOT
SGP
SHE
SI
Recovery room
Recovery room time; Right posterior
temporalis
Reaction time
Resistance temperature device
Revised token test
Random variable
Residual volume; Right ventricle
Right ventricular hypertrophy
Right ventricular outflow tract
Return-to-zero
Sinoatrial; Specific absorption
Solid-ankle-cushion-heel
Source-axis distance; Statistical
Analysis System
System analysis of integrated network
of tasks
Sterility assurance level; Surface
averaged lead
Systematic analysis of language
transcripts
Socially acceptable monitoring
instrument
Systemic arterial pressure
Scatter-air ratio; Specific absorption rate
System for anesthetic and respiratory
gas analysis
Subbacterial endocarditis
Styrene-butadiene rubbers
Stratum corneum; Subcommittees
Right scapula
Saturated calomel electrode; Sister
chromatid exchange
Spinal cord injury
Sub-Committee on Radiation Dosimetry
Spinal cord stimulation
Self-contained underwater breathing
apparatus
Standard deviation
Stepwise discriminant analysis
Sodium dodecyl sulfate
Safety and effectiveness
Standard error
Size exclusion chromatography
Scanning electron microscope; Standard
error of the mean
Somatosensory evoked potential
Surface extended X-ray absorption
fine structure
Surviving fraction
Source-film distance
Stroma-free hemoglobin
Sagittal frontal transverse rotational
Silica gel
Silica gel fraction
Spark gap generator
Serum glutamic oxaloacetic transaminase
Strain gage plethysmography;
Stress-generated potential
Standard hydrogen electrode
Le Syste`me International dUnite s
SEBS
SID
SIMFU
SIMS
SISI
SL
SLD
SLE
SMA
SMAC
SMR
S/N
S:N/D
SNP
SNR
SOA
SOAP
SOBP
SP
SPECT
SPL
SPRINT
SPRT
SPSS
SQUID
SQV
SR
SRT
SS
SSB
SSD
SSE
SSEP
SSG
SSP
SSS
STD
STI
STP
STPD
SV
SVC
SW
TAA
TAC
TAD
TAG
TAH
TAR
TC
TCA
TCD
TCES
xxix
xxx
TCP
TDD
TDM
TE
TEAM
TEM
TENS
TEP
TEPA
TF
TFE
TI
TICCIT
TLC
TLD
TMJ
TMR
TNF
TOF
TP
TPC
TPD
TPG
TPN
TR
tRNA
TSH
TSS
TTD
TTI
TTR
TTV
TTY
TUR
TURP
TV
TVER
TW
TxB2
TZ
UES
UP
UfflS
UHMW
Tricalcium phosphate
Telecommunication devices for the
deaf
Therapeutic drug monitoring
Test electrode; Thermoplastic elastomers
Technology evaluation and acquisition
methods
Transmission electron microscope;
Transverse electric and magnetic mode;
Transverse electromagnetic mode
Transcutaneous electrical nerve
stimulation
Tracheoesophageal puncture
Triethylenepho-sphoramide
Transmission factor
Tetrafluorethylene
Totally implantable
Time-shared Interaction ComputerControlled Information Television
Thin-layer chromatography; Total
lung capacity
Thermoluminescent dosimetry
Temporomandibular joint
Tissue maximum ratio; Topical
magnetic resonance
Tumor necrosis factor
Train-of-four
Thermal performance
Temperature pressure correction
Triphasic dissociation
Transvalvular pressure gradient
Total parenteral nutrition
Temperature rise
Transfer RNA
Thyroid stimulating hormone
Toxic shock syndrome
Telephone devices for the deaf
Tension time index
Transition temperature range
Trimming tip version
Teletypewriter
Transurethral resection
Transurethral resections of the
prostrate
Television; Tidal volume; Tricuspid valve
Transscleral visual evoked response
Traveling wave
Thrombozame B2
Transformation zone
Upper esophageal sphincter
Urea-formaldehyde
University Hospital Information System
Ultra high molecular weight
UHMWPE
UL
ULF
ULTI
UMN
UO
UPTD
UR
US
USNC
USP
UTS
UV
UVR
V/F
VA
VAS
VBA
VC
VCO
VDT
VECG
VEP
VF
VOP
VP
VPA
VPB
VPR
VSD
VSWR
VT
VTG
VTS
VV
WAIS-R
WAK
WAML
WBAR
WBC
WG
WHO
WLF
WMR
w/o
WORM
WPW
XPS
XR
YAG
ZPL
Base Units
length
massz
time
electric current
thermodynamic temperature
amount of substance
luminous intensity
metery (m)
kilogram (kg)
second (s)
ampere (A)
kelvin (K)
mole (mol)
candela (cd)
Supplementary Units
plane angle
solid angle
radian (rad)
steradian (sr)
Quantity
*
absorbed dose
acceleration
*
activity (of ionizing radiation source)
area
Unit
gray
meter per second squared
becquerel
square kilometer
square hectometer
square meter
Symbol
Gy
m/s2
Bq
km2
hm2
m2
Acceptable equivalent
J/kg
1/s
ha (hectare)
The spellings metre and litre are preferred by American Society for Testing and Materials (ASTM); however, er will be
used in the Encyclopedia.
z
Weight is the commonly used term for mass.
Wide use is made of Celsius temperature t defined t T T0 where T is the thermodynamic temperature, expressed in
kelvins, and T0 273:15 K by definition. A temperature interval may be expressed in degrees Celsius as well as in kelvins.
xxxi
xxxii
Quantity
equivalent
*
capacitance
concentration (of amount of substance)
*
conductance
current density
density, mass density
dipole moment (quantity)
*
electric charge, quantity of electricity
electric charge density
electric field strength
electric flux density
*
electric potential, potential difference,
electromotive force
*
electric resistance
*
energy, work, quantity of heat
energy density
*
force
*
frequency
illuminance
inductance
linear density
luminance
*
luminous flux
magnetic field strength
*
magnetic flux
*
magnetic flux density
molar energy
molar entropy, molar heat capacity
moment of force, torque
momentum
permeability
permittivity
*
power, heat flow rate, radiant flux
*
sound level
specific energy
specific volume
surface tension
thermal conductivity
velocity
viscosity, dynamic
y
Unit
Symbol
Acceptable
farad
mole per cubic meter
siemens
ampere per square meter
kilogram per cubic meter
coulomb meter
coulomb
coulomb per cubic meter
volt per meter
coulomb per square meter
F
mol/m3
S
A/m2
kg/m3
Cm
C
C/m3
V/m
C/m2
C/V
volt
ohm
megajoule
kilojoule
joule
electron volty
kilowatt houry
joule per cubic meter
kilonewton
newton
megahertz
hertz
joule per kelvin
joule per kilogram kelvin
watt per square meter
kelvin
lux
henry
kilogram per meter
candela per square meter
lumen
ampere per meter
weber
tesla
joule per mole
joule per mole kelvin
newton meter
kilogram meter per second
henry per meter
farad per meter
kilowatt
watt
V
V
MJ
kJ
J
eVy
kWhy
J/m3
kN
N
MHz
Hz
J/K
J/(kgK)
W/(m2K)
W/m2
MPa
kPa
Pa
dB
J/kg
m3/kg
N/m
W/(mK)
m/s
km/h
Pas
mPas
lx
H
kg/m
cd/m2
lm
A/m
Wb
T
J/mol
J/(molK)
Nm
kgm/s
H/m
F/m
kW
W
A/V
g/L; mg/cm3
As
W/A
V/A
Nm
kgm/s2
1/s
lm/m2
Wb/A
cdsr
Vs
Wb/m2
J/s
N/m2
This non-SI unit is recognized as having to be retained because of practical importance or use in specialized fields.
Quantity
viscosity, kinematic
Unit
square meter per second
square millimeter per second
cubic meter
cubic decimeter
cubic centimeter
1 per meter
1 per centimeter
wave number
Symbol
m2/s
mm2/s
m3
dm3
cm3
m1
cm1
xxxiii
Acceptable equivalent
L(liter)
mL
Multiplication factor
1018
1015
1012
109
108
103
102
10
101
102
103
106
109
1012
1015
1018
Prefix
exa
peta
tera
giga
mega
kilo
hecto
deka
deci
centi
milli
micro
nano
pico
femto
atto
Symbol
E
P
T
G
M
k
ha
daa
da
ca
m
m
n
p
f
a
Note
For a complete description of SI and its use the reader is referred to ASTM E 380.
To
square meter (m2)
meter (m)
square meter (m2)
meter (m)
pascal (Pa)
pascal (Pa)
cubic meter (m3)
joule (J)
joule (J)
joule (J)
cubic meter (m3)
joule (J)
joule (J)
joule (J)
pascal (Pa)
pascal second (Pas)
square millimeter per second (mm2/s)
Multiply by
4:047 103
1:0 1010y
1:0 102y
1:496 1011
1:013 105
1:0 105y
0.1590
1:055 103
1:056 103
1:054 103
3:524 102
4.187
4.190
4.184y
98.07
1:0 103y
1.0y
xxxiv
To convert from
cfm (cubic foot per minute)
cubic inch
cubic foot
cubic yard
curie
debye
degree (angle)
denier (international)
dram (apothecaries)
dram (avoirdupois)
dram (U.S. fluid)
dyne
dyne/cm
electron volt
erg
fathom
fluid ounce (U.S.)
foot
foot-pound force
foot-pound force
foot-pound force per second
footcandle
furlong
gal
gallon (U.S. dry)
gallon (U.S. liquid)
gilbert
gill (U.S.)
grad
grain
gram force per denier
hectare
horsepower (550 ftlbf/s)
horsepower (boiler)
horsepower (electric)
hundredweight (long)
hundredweight (short)
inch
inch of mercury (32 8F)
inch of water (39.2 8F)
kilogram force
kilopond
kilopond-meter
kilopond-meter per second
kilopond-meter per min
kilowatt hour
kip
knot international
lambert
league (British nautical)
league (statute)
light year
liter (for fluids only)
maxwell
micron
mil
mile (U.S. nautical)
mile (statute)
mile per hour
To
cubic meter per second (m3/s)
cubic meter (m3)
cubic meter (m3)
cubic meter (m3)
becquerel (Bq)
coulomb-meter (Cm)
radian (rad)
kilogram per meter (kg/m)
tex
kilogram (kg)
kilogram (kg)
cubic meter (m3)
newton(N)
newton per meter (N/m)
joule (J)
joule (J)
meter (m)
cubic meter (m3)
meter (m)
joule (J)
newton meter (Nm)
watt(W)
lux (lx)
meter (m)
meter per second squared (m/s2)
cubic meter (m3)
cubic meter (m3)
ampere (A)
cubic meter (m3)
radian
kilogram (kg)
newton per tex (N/tex)
square meter (m2)
watt(W)
watt(W)
watt(W)
kilogram (kg)
kilogram (kg)
meter (m)
pascal (Pa)
pascal (Pa)
newton (N)
newton (N)
newton-meter (Nm)
watt (W)
watt(W)
megajoule (MJ)
newton (N)
meter per second (m/s)
candela per square meter (cd/m2)
meter (m)
meter (m)
meter (m)
cubic meter (m3)
weber (Wb)
meter (m)
meter (m)
meter (m)
meter (m)
meter per second (m/s)
Multiply by
4:72 104
1:639 104
2:832 102
0.7646
3:70 1010y
3:336 1030
1:745 102
1:111 107
0.1111
3:888 103
1:772 103
3:697 106
1:0 106y
1:00 103y
1:602 1019
1:0 107y
1.829
2:957 105
0.3048y
1.356
1.356
1.356
10.76
2:012 102
1:0 102y
4:405 103
3:785 103
0.7958
1:183 104
1:571 102
6:480 105
8:826 102
1:0 104y
7:457 102
9:810 103
7:46 102y
50.80
45.36
2:54 102y
3:386 103
2:491 102
9.807
9.807
9.807
9.807
0.1635
3.6y
4:448 102
0.5144
3:183 103
5:559 102
4:828 103
9:461 1015
1:0 103y
1:0 108y
1:0 106y
2:54 105y
1:852 103y
1:609 103
0.4470
To convert from
To
Multiply by
millibar
millimeter of mercury (0 8C)
millimeter of water (39.2 8F)
minute (angular)
myriagram
myriameter
oersted
ounce (avoirdupois)
ounce (troy)
ounce (U.S. fluid)
ounce-force
peck (U.S.)
pennyweight
pint (U.S. dry)
pint (U.S. liquid)
poise (absolute viscosity)
pound (avoirdupois)
pound (troy)
poundal
pound-force
pound per square inch (psi)
quart (U.S. dry)
quart (U.S. liquid)
quintal
rad
rod
roentgen
second (angle)
section
slug
spherical candle power
square inch
square foot
square mile
square yard
store
stokes (kinematic viscosity)
tex
ton (long, 2240 pounds)
ton (metric)
ton (short, 2000 pounds)
torr
unit pole
yard
pascal (Pa)
pascal (Pa)
pascal (Pa)
radian
kilogram (kg)
kilometer (km)
ampere per meter (A/m)
kilogram (kg)
kilogram (kg)
cubic meter (m3)
newton (N)
cubic meter (m3)
kilogram (kg)
cubic meter (m3)
cubic meter (m3)
pascal second (Pas)
kilogram (kg)
kilogram (kg)
newton (N)
newton (N)
pascal (Pa)
cubic meter (m3)
cubic meter (m3)
kilogram (kg)
gray (Gy)
meter (m)
coulomb per kilogram (C/kg)
radian (rad)
square meter (m2)
kilogram (kg)
lumen (lm)
square meter (m2)
square meter (m2)
square meter (m2)
square meter (m2)
cubic meter (m3)
square meter per second (m2/s)
kilogram per meter (kg/m)
kilogram (kg)
kilogram (kg)
kilogram (kg)
pascal (Pa)
weber (Wb)
meter (m)
1:0 102
1:333 102y
9.807
2:909 104
10
10
79.58
2:835 102
3:110 102
2:957 105
0.2780
8:810 103
1:555 103
5:506 104
4:732 104
0.10y
0.4536
0.3732
0.1383
4.448
6:895 103
1:101 103
9:464 104
1:0 102y
1:0 102y
5.029
2:58 104
4:848 106
2:590 106
14.59
12.57
6:452 104
9:290 102
2:590 106
0.8361
1:0y
1:0 104y
1:0 106y
1:016 103
1:0 103y
9:072 102
1:333 102
1:257 107
0.9144y
xxxv
R
continued
INTRODUCTION
The use of subatomic particles to treat cancer and other
medical conditions can be traced back (1) to the discovery of
natural radioactivity by Bequerel in 1896. Marie Sklodowska Curie and her husband Pierre Curie quickly identified the primary radiation emitted by radioactive
materials such as uranium and thorium as consisting of
three principal types: a, b, and g rays. Among these rays,
only g rays, being high energy photons, are a form of
electromagnetic radiation. Therefore, they are similar to
lower energy photons and, in particular, X rays with regard
to their interaction in matter (24).
In contrast, the a and b rays were observed to be much
more ionizing than g rays, and unlike g rays had a finite range
in materials. The latter feature is characteristic of energetic
subatomic particles and, indeed, the a ray was later identified
as an energetic 4 He ion. It is emitted via nuclear a decay from
heavy radioactive elements. Likewise, b rays were identified
as energetic electrons emitted via nuclear b decay from light
and heavy radioactive elements. Subsequently, the Curies
were able to identify one particular highly radioactive element, radium. With considerable time and effort, they were
able to extract small but usable pure samples of this from
large amounts of uranium ore. As is also the case with X rays,
workers using strong radioactive sources, including the
Curies, often developed skin rashes and other symptoms
related to exposure to natural radiation from radioactive
materials. Medical doctors quickly realized that this radiation also could be used in medical applications.
Thus, following closely on the work by Roentgen et al. on
the application of manmade radiation (i.e., X rays) to treat
cancer, the Curies and others used radium and other
natural radioactive sources to treat cancer tumors (Fig. 1)
(1). Although the a, b, and g rays emitted from nuclear
decay were emitted with a much higher energy (MeV vs
keV for X rays), the a and b particles had very short ranges
in tissue (e.g., a mm or less for a particles and a few cm for
b particles). Therefore, these sources, particularly including the associated MeV gamma rays, primarily were used
to treat surface tumors (Fig. 1). An early form of bracyatherapy using radioactive needles also was developed
to treat deeper tumors (1).
WHERE
WHAT
Berkeley 184
Berkeley
Uppsala (1)
Harvard
Dubna (1)
ITEP, Moscow
Los Alamos
St. Petersburg
Berkeley
Chiba
TRIUMF
PSl (SIN)
PMRC (1), Tsukuba
PSI (72 MeV)
Uppsala (2)
Clatterbridge
Loma Linda
Louvain-la-Neuve
Nice
Orsay
iThemba LABS
MPRI (1)
UCSF - CNL
HIMAC, Chiba
TRIUMF
PSI (200 MeV)
G.S.I Darmstadt
H.M.I, Berlin
NCC, Kashiwa
Dubna (2)
HIBMC, Hyogo
PMRC (2), Tsukuba
NPTC, MGH
HIBMC, Hyogo
INFN-LNS, Catania
WERC
Shizuoka
MPRI (2)
Wanjie, Zibo
CA. USA
CA. USA
Sweden
MA. USA
Russia
Russia
NM. USA
Russia
CA. USA
Japan
Canada
Switzerland
Japan
Switzerland
Sweden
England
CA, USA
Belgium
France
France
South Africa
IN USA
CA USA
Japan
Canada
Switzerland
Germany
Germany
Japan
Russia
Japan
Japan
MA USA
Japan
Italy
Japan
Japan
IN USA
China
p
He
p
p
p
p
p
p
ion
p
p
p
p
p
p
p
p
p
p
p
p
p
p
C ion
p
p
C ion
p
p
p
p
p
p
C ion
p
p
p
p
p
DATE
FIRST RX
1954
1957
1957
1961
1967
1969
1974
1975
1975
1979
1979
1980
1983
1984
1989
1989
1990
1991
1991
1991
1993
1993
1994
1994
1995
1996
1997
1998
1998
1999
2001
2001
2001
2002
2002
2002
2003
2004
2004
DATE LAST RX
1957
1992
1976
2002
1996
1982
1992
1994
1993
2000
1993
1999
TOTAL
RECENT
PATIENT TOTAL
30
2054
73
9116
124
3785
230
1145
433
145
367
503
700
4182
418
1372
9585
21
2555
2805
468
34
632
1796
89
209
198
546
300
296
483
492
973
30
82
19
100
21
1
1100
4511
40801
46412
DATE
OF TOTAL
Dec-04
April-04
Apr-02
Dec-04
Jan-04
Dec-04
Nov-04
April-04
Dec-03
Nov-04
June-04
Feb-04
Dec-03
Dec-04
Dec-03
Dec-04
Oct-04
Dec-04
Dec-04
July 04
Dec-04
Dec-02
Oct-04
Oct-04
Dec-04
July-04
Dec-04
pions
ions
protons
all particles
physics, LET is usually specified in keV/mm or, alternatively, keV/g/cm2 for a specific medium. Specifically, in a
given material, the LET for a charged, nonrelativistic
heavy particle of mass m and atomic number z moving
at a velocity v [hence, kinetic energy E (1/2)mv2] has the
behavior (25)
LET k z2 =v2
(1)
K z2 =E=m
where k and K are constants that depend on the atomic
composition of the medium. Suitable integration of LET
from E incident E ( E0) to E 0 then gives the range,
R of the particle in the medium. Based on the above, we
would expect R to then be proportional to E0n with n 2,
which is approximately true but, because of various
p (66) / Be neutrons
SSD = 150 cm
100
Relative dose
80
8 MV X-rays
SSD = 100 cm
60
Co
SSD = 80 cm
60
40
20
20 MeV electrons
0
0
10
15
20
25
30
atomic effects (25), one typically has 1.4 < n < 2 depending on z and E0.
Owing to the 1/E dependence of LET (Eq. 1, above),
protons, alphas, and heavier particles such as 12 C ions
exhibit a very high LET at the end of their range, resulting
in a sharp Bragg peak (Fig. 2). In cancer treatment, this
sharp LET peak is often then spread out using energy-loss
absorbers or other means to produce a spread-out Bragg
peak (SOBP) suitable for treating an extended tumor
(Fig. 3).
In the case of heavy particles, the biological dose will
depend on the LET as well as the relative biological effectiveness (RBE) of the incident particle (2). The RBE may
a
Dose
Depth
Figure 3. Illustration showing modification of a particle depthdose curve by means of a spread-out Bragg peak (SOBP; adapted
from Ref. 5).
Ar
1999
High Energy
Neutrons
Si
Neutron
IMRT
Ne
Pions
250 kVp
X-rays
60
Co
4 MV
X-rays
22 MV
X-rays
C
MV
X-ray
IMRT
Incident beam
65% Pions
25% Electrons
10% Muons
P0 = 190 MeV/c
"Stars"
ELECTRON-BEAM RADIOTHERAPY
1
Pions
Mouns
0
0
Electrons
10
20
30
Centimeters of water
40
Table 2. Summary of Present External Beam Radiotherapy Options for Malignant Tumorsa
Accelerator costb
Particle
Tumor Characteristics
Energy deposition
Bragg peak
Radiation source
Photons
Rapidly growing,
oxygenated
Superficial
Early stage, near-critical
structures
Slow growing, hypoxic
Same as fast neutrons
Same as fast neutrons
Glioblastoma;
Some melanomas
Low LET
No
Low LET
Low LET
No
Yes
12
1015
High LET
High LET
High LET
Very high LET
with BNCT
No
Yes
Yes
No
810
40
3540
12
Electrons
Protons
Fast neutrons
Heavy ions
Pions
Slow neutrons
(Fig. 7) (8). The electron LINAC usually is used in conjunction with an isocentric gantry (Fig. 8) (8) to permit
stereotactic treatment with minimal movement of the
patient.
In principle, with an electron beam of sufficient intensity and energy, the direct beam also can be used for
radiotherapy. However, as noted, the large collisional
scattering of the electrons in tissue results in a large
angular spread (i.e., penumbra) (2) of the beam (Fig. 4),
which limits the usefulness of the direct beam for therapy
other than for treatment of skin cancer, other shallow
tumors, or for noncancerous skin diseases (Table 2). However, owing to their compactness, a gantry-mounted electron-beam system (Fig. 8) can also be used in an operating
room to directly irradiate an internal tumor (or surrounding area) made accessible via surgery. This technique,
interoperative electron-beam radiation therapy (IOERT),
may be particularly advantageous for treatment of certain
types of cancers when combined with more conventional
treatment (37).
Vacuum system
Steering coils
Focusing coils
Steering coils
Electron gun
Accelerating waveguide
Target
Exit
window
Primary
collimators
Circulator
Pulsed
modulator
Control unit
Microwave
power
source
Gas
pressure
system
Flattening
filter
Dual ion
chamber
Upper
jaws
Water
cooling
system
Multileaf collimator
Lower
jaws
Figure 7. Schematic diagram of an electron LINAC of the type used for radiation therapy (8).
Rf power
generator
Electron
gun
Accelerating
waveguide
(a)
X-ray
target
Gentry
axis
Isocenter
Couch
axis
Accelerating
waveguide
Electron
gun
X-ray
target
Gentry
axis
(b)
Isocenter
Couch
Couch
axis
Rf power
generator
Electron
gun
X-ray
target
Accelerating
waveguide
Gentry
axis
Isocenter
(c)
Couch
Figure 8. Various isocentric gentry arrangements used with electron accelerators for radiation treatment using secondary X rays or the
direct electron beam (8).
Rf power
generator
Couch
axis
1930s (6). Hence, fast neutrons were used in cancer treatment well before high energy protons, a, and other heavy
particles became available.
As a neutron therapy beam is produced as a secondary
beam from a nuclear reaction on a production target with a
primary charged-particle beam, the associated accelerator
generally must have a high primary beam current (e.g., a
proton or deuteron beam at the mA level). The accelerator
facility also must then have the necessary massive shielding for fast neutrons. In some cases, the primary accelerator also can then be used to produce radioisotopes (such
as 18F and 11C) that can be used for positron emission
tomography (PET). Like other early cancer-therapy accelerators, most of the first-generation fast-neutron treatment
facilities were adjuncts to nuclear research facilities.
Recently, several new dedicated fast-neutron treatment
facilities have become available (6,23,45).
Neutrons in tissue (and other material) behave quite
differently than protons, a particles, or other heavy
charged particles. Specifically, being uncharged, the dose
Coil
Extraction
Correction
magnets
Beam
monitors
Sector 2
Sector 2
Injection
Sector 1
Sector 1
Cavity
10
20
30
cm
Yoke
Figure 9. Compact race-track electron microtron used to produce high energy electrons; E > 25 MeV (36).
Proton-Beam Radiotherapy
high cross section for the reaction 10B (n, a) and produces
(Fig. 11) (23) highly localized, low energy a particles
(1.47 MeV) and 7Li recoil ions (0.8 MeV), which quickly
stop, yielding a highly localized LET that greatly enhances
the local dose to a tumor. The boron is preferentially
attached to the tumor site using a tumor-specific boronloaded pharmaceutical (46,47). As this technique works
particularly well with slow neutrons (keV to MeV), it can be
used with slow or low energy neutrons produced from small
accelerators or from nuclear reactors, which is the basis for
boron-neutron capture therapy (BNCT), and a number of
clinical trials using BNCT are underway, primarily outside
of the United States.
Related to BNCT, the manmade isotope 252Cf, which
produces both energetic a particles (Ea 6.1 MeV)
together with fission fragments and associated fission
neutrons (En 23 MeV), has been proposed (46,47),
together with boron-loaded tumor-specific compounds, as
a special form of BNCT brychatherapy.
Slow n
10B
11B*
7L (E
i
= 0.48 MeV)
BNCT
Figure 11. Illustration of the nuclear processes involved in BNCT
(adopted from Ref. 23).
Excluding electron beams, which, as noted, have limitations for treatment of deep tumors, protons are presently
the primary beams used in particle-beam therapy. A number of cyclotrons, originally operated as nuclear research
facilities, have since been converted for use as medical
treatment facilities (Table 1). A conventional cyclotron
i.e., one that uses a fixed radio frequency (RF) accelerating
voltage and a single large conventional magnet (6) is
typically limited in proton beam energy to less than
80 MeV, which limits the penetration depth to less than
a few cm in tissue (Fig. 2). Hence, these facilities (about
one-third of all proton-beam therapy facilities) are generally limited to treatment of shallow tumors, especially eye
tumors, or for treatment of certain noncancerous conditions such as age-induced macular degeneration (AMD)
(10,12,48,49). As many of these facilities are located in a
nuclear research laboratory rather than in or near a hospital, certain treatments requiring fractionated doses or
treatment done in combination with other modalities can
be problematic.
Treatment of deep-seated tumors requires a proton
beam energy of 200 MeV or more (Fig. 2). At this energy,
the protons relativistic increase of mass with increasing
velocity requires the use of a large separated-sector cyclotron or high field cyclotron, such as those in use at Indiana
University, Massachusetts General Hospital (Fig. 12) (49),
and elsewhere, or a race track synchrotron adapted from
high energy physics. An example of the latter is the synchrotron at the Loma Linda proton-beam treatment facility
(49). Synchrotrons are also generally used to produce
heavier particles [e.g., 12C ions used for radiation treatment (see below)].
A cyclotron produces a beam with a 100% macroscopic
duty cycle, although it still has a beam modulated by the
accelerating voltage RF, typically tens of MHz (6). The
synchrotron produces a beam modulated by the ramping
time of the variable-field accelerator magnets. The latter
can be on the order of seconds (6), which generally is not a
problem in radiation therapy and can be used as an advantage in some treatments. A third type of accelerator, the
synchro-cyclotron, developed after WWII at LBL and used
at LBL for a-beam radiotherapy for many years, is presently only in limited use (Table 1).
As the direct proton beam in these accelerators is used for
therapy, only a modest beam intensity is required relative to
the beam intensities needed for a nuclear research accelerator or one used to produce neutrons or pions, viz. namps
vs mamps, which can simplify the accelerator design, the
building, and shielding required . However, in some cases, a
high intensity beam is desirable in order to produce radioisotopes used in PET and other imaging methods.
All types of proton facilities, owing to the high magnetic-rigidity of high energy protons, require a set of large
(and costly) beam-switching magnets and patient-treatment gantries (Fig. 13) (49). Likewise, raster-scanning
the beam and varying the dose-depth required to treat a
particular tumor is not trivial, which can be done (Fig. 14)
(49) with electronic elements (active scanning) or with
shaped absorbers (passive modulation).
10
Figure 14. Schematics of typical passive and active ion-beam raster-scanning apparatus used to generate suitable dose profiles for
treatment of specific tumors. (Reprinted with permission from Ref. 49, copyright 2002 American Physical Society.)
11
HI treatments involve fractionated doses, and the HI therapy is often used in conjunction with other treatment
modalities such as chemotherapy or photon therapy. Like
other pioneering particle-beam facilities, GSI is a nuclear
research facility and not a priori part of a hospital facility,
which can often limit patient throughput. Nonetheless,
several hundred patients have been treated since 1997
(Table 1). Based on the results demonstrated, the GSI
nuclear and biomedical research group together with a
hospital facility in Heidelberg, Germany is finishing the
constructing of a dedicated HI accelerator and HI treatment facility. This facility is expected to become fully
operational in mid-2005 and will serve as a German
national treatment facility for the 3000 or more patients
identified as optimal for HI therapy each year in Germany.
A similar facility is under contruction in Italy (12).
At present (2005), the primary facilities built and dedicated to HI cancer therapy are the HIBMC and HIMAC
facilities (53) in Japan (Fig. 16) (54). As at GSI, these
facilities primarily use 12C ions at energies of several
hundred MeV/nucleon. (HIBMC also has the capability
to use protons in radiotherapy). Several thousand patients
have been treated at HIBMC and HIMAC (Table 1). Like
proton therapy facilities, the large footprint (Fig. 16) and
costs associated with an HI accelerator and the associated
treatment facilities will generally limit their availability.
In countries with national health services, one, two, or at
most three HI facilities may accommodate those patients
who might benefit from HI therapy. The situation becomes
complicated in countries like the United States where
private insurers must approve treatment.
FUTURE DEVELOPMENTS
Magnetically-Confined Electron Beams
It has been suggested, and recently demonstrated with
experiments, that one might use high energy electrons
(E 100 MeV) for radiotherapy with suitable magnetic
fields applied to reduce (Fig. 17)(21) the pneumbra from
scattering (21, 3144). Again, if the direct electron beam
is used, relatively low intensity beams can be used, which
simplifies the accelerator, beam handling, and shielding.
Most hospitals operate and maintain electron accelerators
(E 1025 MeV), mostly LINACs, for radiation therapy
12
Figure 16. Layout of the HI-beam cancer treatment facility HIMAC in Chiba, Japan (adopted from Ref. 54).
RADIOTHERAPY, INTRAOPERATIVE
Pulsed-Laser Accelerators
It is now possible to produce very high electric fields in
plasmas using compact ultra-fast pulsed lasers, which can
be used to accelerate electrons, protons, and other ions to
MeV energies (38). Although the particle-beam intensities
and, in some cases, energies demonstrated so far are less
than those needed for radiotherapy, such table-top accelerators may prove viable in the future.
ACKNOWLEDGMENTS
The author thanks J. Sisterson, Ph.D., Yu Chen, Ph.D.,
D. Litzenberg, Ph.D., Prof. L. Jones, and Hao Jiang for
their assistance.
References are on page 609.
See also IONIZING RADIATION, BIOLOGICAL EFFECTS OF; RADIATION DOSIMETRY
FOR ONCOLOGY; RADIOTHERAPY TREATMENT PLANNING, OPTIMIZATION OF.
RADIOTHERAPY, INTRAOPERATIVE
PETER J. BIGGS
Harvard Medical School
Boston, Massachusetts
INTRODUCTION
What Is Intraoperative Radiotherapy?
Intraoperative radiotherapy (IORT) is a technique that
combines radiation therapy with surgery to irradiate
tumors in situ, without delivering a significant dose to
surrounding normal, critical structures and is usually
performed using electron beams from linear accelerators.
This contrasts with external beam therapy using X-ray
beams where the dose that can safely be delivered to most
tumors is limited by the dose that is given consequentially
to normal, critical structures.
The practice of IORT began soon after X rays were used
therapeutically, almost 100 years ago. However, although
several investigators used this technique over the ensuing
years with various X-ray modalities, it was not until the
mid-1960s that intraoperative radiotherapy made a serious mark on the field of radiotherapy with the work of Abe
(14) in Japan using electron beams from linear accelerators. This was rapidly followed in the mid-1970s by investigations in the United States, first at Howard University
(5), then at the Massachusetts General Hospital (MGH) (6),
followed by the National Cancer Institute (7), and then the
Mayo Clinic (8). The reason for this dramatic change was
due to the introduction of linear accelerators capable of
generating high energy electron beams.
In 1992, Coia and Hanks (9) reported on patterns of care
study, which indicated that of 1293 radiation oncology
facilities in the United States, 108 reported doing IORT,
of which 29 have two or more residents. Since there were
88 training programs in existence at that time, roughly
one-third of hospitals or medical centers with residency
training programs were performing IORT. They did not
13
14
RADIOTHERAPY, INTRAOPERATIVE
Electron beam
Screw to
fix block
in tube
Quartz halogen
light source
Mirror
Lucite
block
Observer
Lucite tube
Aluminum tube
Intra-op cone
Surface
RADIOTHERAPY, INTRAOPERATIVE
viewed even after the docking is complete. The disadvantage of this method is that an alternative to the simple
mechanical alignment is needed. This need has been
answered by a variety of optical systems as explained below.
A description of two commercial alignment systems is given
below. A description of several noncommercial soft-docking
systems has been published by several authors (1417).
The Clinical Rationale for IORT
To understand the rationale for intraoperative radiotherapy, it is necessary to understand some of the basic principles of radiotherapy. Patients are routinely treated for
cancer using fractionated radiation. This means that the
radiation is delivered in increments on a daily basis, 5 days
week1 for up to 8 weeks, depending on the lesion under
treatment. The reason for doing this is that if one were to
deliver a tumoricidal amount of radiation to the tumor in
one or a few fractions, serious long-term side effects to
normal tissue and organs would result. By fractionating
the radiation, an equivalent tumoricidal dose can be given
to the tumor without serious long-term side effects. Fractionation schemes currently in use have developed empirically over the history of radiotherapy going back to the use
of early X-ray tubes. The daily fraction dose is limited by
acute radiation effects. These effects, such as reddening of
the skin in the era of low energy X rays, bowel problems,
and so on, appear during the course of treatment, but will
generally resolve themselves without long-term consequences after the radiation treatment has been completed.
This maximum radiation dose may produce acute effects in
a few patients, due to biological variation between individuals and, hence, their response to radiation. The prescription dose or the maximum overall dose, which is the
number of daily fractions times the daily dose, is also
limited. This limit is due to normal tissue and organ
tolerance. Thus, for example, abdominal radiation for rectal or colon cancer is limited to 50 Gy because of small
bowel complications (Gy is the unit of absorbed dose and is
expressed in J
kg1). The kidneys can tolerate a dose of no
more than 15 Gy and treatment for lung cancer requires
keeping the dose to the spinal cord below 45 Gy to avoid
transverse myelitis. Some organs, such as the liver, can
tolerate varying amounts of radiation, depending on the
fraction of liver that is irradiated. The smaller the fraction
of organ treated, the larger the dose that can be tolerated.
Excess dose to the whole lung can produce fibrosis, resulting in a nonfunctional lung. However, even with these dose
limits, local control rates, or control of the primary tumor
that is being irradiated is not 100%, so it would be highly
desirable to have a method for increasing the dose to the
tumor without increasing the dose to the surrounding
normal tissue. This is known as improving the therapeutic
ratio, which, for a given dose fractionation, is defined as
IORT Single
Dose, Gy
Therapeutic ratio
tumor control probability=normal tissue
complication probability
Ideally, this ratio should be as high as possible. One
method to improve this ratio is through the use of intraoperative irradiation. In this technique, the area to be
15
10
15
20
25
a
2 Gy fractions.
Equivalent Dose
for Late
Normal Tissue
Reactionsa
17
31
50
73
26
54
92
140
16
RADIOTHERAPY, INTRAOPERATIVE
Number of Institutions
6 (15.8%)
4 (10.5%)
8 (21.1%)
9 (23.7%)
2 (5.3%)
5 (13.2)
4 (10.5)
Number of
Institutions
11 (31.6%)
5 (13.2%)
21 (55.3)
6 (15.8%)
7 (18.4%)
2a (5.3%)
RADIOTHERAPY, INTRAOPERATIVE
IORT TECHNOLOGY
Early Technology
Radiotherapy prior to the 1960s used primarily X-ray
machines for the treatment of cancer patients, although
in the years just before that Cobalt-60 teletherapy units
were coming into widespread use. Schultz (30) describes in
great detail the history of the development of X-ray
machines of increasing energy. Thus, in the early days,
X-ray machines were the only modality to carry out IORT.
In the earliest applications of IORT, Practitioners used
50 kV X rays with a focus-to-skin (FSD) distance of 2 cm
with a field size (diameter) of about the same dimension,
varying the filtration to achieve sufficient penetration.
Henschke and Henschke (31) provide considerable detail
on the practical application of this technique to the treatment of large fields. They show that this can be accomplished either by increasing the FSD, primarily to increase
the percent depth dose, or by use of multiple, overlapping
fields at short FSD. Thus, until X-ray machines operating
at higher energies with adequate dose rates at larger
distances and covering larger fields became available,
the role of IORT was relatively limited. Beginning in the
late 1930s through the 1940s, such high energy units
became available. Eloesser (32) described the use of an
X-ray machine with filtrations between 0.25 and 0.5 mm
Cu. He notes that the filtration depends on the thickness of
the tumor being treated; the FSD was 30 cm. In 1947,
Fairchild and Shorter (33) describe a technique using
250 kV X rays with a half value layer (HVL) of 1.7 mm
Cu. At a FSD of 21.7 cm, a dose rate of 100 R
min1 could be
delivered over a 13 cm field diameter. Note that since these
high energy X-ray beams were not collimated, lead sheets
had to be placed around the surgical opening and internal
viscera to provide adequate radiation protection.
Whereas the difficulty of using low energy X-ray beams
is one of insufficient penetration, the problem with high
energy X-ray beams is that, although their intensity is
exponentially attenuated, tissues or organs beneath the
tumor to be treated can receive a considerable dose of
radiation. For this reason and many technical reasons
associated with using an X-ray machine in an OR, it is
clear that IORT could not have been anything other than
an experimental technique pursued by a few investigators.
Recent IORT Technology: Photons versus Electrons
In the 1960s, the first linear accelerators appeared in
clinical use for the treatment of cancer. One of the first
units in the United States was a 6 MV machine (Varian
Medical Associates, Palo Alto, CA), which produced a
bremsstrahlung X-ray beam from a beam of 6 MeV electrons. However, it was not until the 1970s that linear
accelerators were capable of producing clinical electron
beams. Omitted from this historical review is a discussion
of the betatron. Designed and built in the early 1940s by
Donald Kerst, the first patient was treated with X rays in
120
Percent depth dose
17
100
80
18 MeV
60
15 MeV
40
12 MeV
9 MeV
6 MeV
20
0
0
20
40
60
80
100
Depth in water (mm)
120
140
18
RADIOTHERAPY, INTRAOPERATIVE
RADIOTHERAPY, INTRAOPERATIVE
19
Mobetron. The first Mobetron was installed and treated its first patient in 1997. There are currently 12 Mobetron units installed worldwide, 7 operating in the United
States, 1 in Japan, and 4 in Europe. This unit operates with
electron energies of 4, 6, 9, and 12 MeV. A view of this unit
is shown in Fig. 5. The unit is mounted on a gantry,
cantilevered with a beam stopper to intercept the X-ray
component of the primary beam after it has passed through
the patient. This ensures that the radiation exposure in the
room below is sufficiently low as to be within the limits set
for the general public and is the principal feature that
allows this unit to be used in any OR without additional
shielding. Although the unit is gantry mounted, the beam
direction is not limited to the plane of gantry rotation, as
20
RADIOTHERAPY, INTRAOPERATIVE
6
9
12
15
18
1.7
2.6
3.7
4.5
5.1
RADIOTHERAPY, INTRAOPERATIVE
21
0.4
0.3
0.2
0.1
0.0
6
12
Energy (MeV)
15
18
Table 5. Comparison among the Three Methods of IORT Using Linear Accelerators
Mode of IORT
Advantages
Disadvantages
Linac in oncology
department (patient
transport)
Dedicated conventional
linac in OR
Mobile accelerator
22
RADIOTHERAPY, INTRAOPERATIVE
RADIOTHERAPY, INTRAOPERATIVE
23
24
RADIOTHERAPY, INTRAOPERATIVE
Parameter
Daily
Output constancy
Energy constancy
Door interlocks
Mechanical motions
Docking system
Output constancy
Energy constancy
Flatness and symmetry constancy
Docking system
Emergency off buttons
Output calibration for reference conditions
Percent depth dose for standard applicator
Percent depth dose for selected applicators
Flatness and symmetry for standard applicator
Flatness and symmetry for selected applicators
Applicator output factors
Monitor chamber linearity
Output, percent depth dose and profile constancy
over the range of machine orientations
Inspection of all devices normally kept sterile
Monthly
Annual
RADIOTHERAPY, INTRAOPERATIVE
25
1000
100
10
1
0
10
15
20
25
30
35
Distance in water (mm)
40
45
50
26
RADIOTHERAPY, INTRAOPERATIVE
Figure 17. View of the HDR system with one catheter hooked
up to a well chamber for calibration of the source by a medical
physicist.
RADIOTHERAPY, INTRAOPERATIVE
27
EBRT
EBRTIORT
No. Pts
Median (month)
17
56
18
40
35%
70%
24%
55%
24%
46%
No IOERT
IORT/-EBRT
No. Pts
Median (month)
64
42
17
30
26%
62%
18%
43%
7%
19%
28
RADIOTHERAPY, INTRAOPERATIVE
RADIOTHERAPY, INTRAOPERATIVE
18. Sindelar WF, Johnstone PAS, Hoekstra HJ, Kinsella TJ.
Normal tissue tolerance to intraoperative irradiation. In:
Gunderson LL, Willett CG, Harrison LB, Calvo FA, editors.
Intraoperative Irradiation: Techniques and Results. Totowa,
(NJ): Humana Press; 1999.
19. Gillette EL, Gillette SM, Powers BE. Studies at Colorado
State University of normal tissue tolerance of beagles to
IOERT, EBRT or a combination. In: Gunderson LL, Willett
CG, Harrison LB, Calvo FA, editors. Intraoperative Irradiation: Techniques and Results. Totowa, (NJ): Humana Press;
1999.
20. Hall EJ. Radiology for the radiologists. Hagerstown, (MD):
Harper and Row; 1978.
21. Nag S et al. Intraoperative irradiation with electron-beam or
high-dose-rate brachytherapy: Methodological comparisons.
In: Gunderson LL, Willett CG, Harrison LB, Calvo FA,
editors. Intraoperative Irradiation: Techniques and results.
Totowa, (NJ): Humana Press; 1999.
ber Kombinationsbehandlung bei bo sartigen Neu22. Beck C. U
bildungen. Berl Klin Wochenstr 1907;44:1335.
23. Beck C. On external Roentgen treatment of internal structures (eventration treatment). N Y Med J 1909;89:621622.
24. Finsterer H. Zur Therapie inoperabler Magen- und Darmkarzinome mit Freilegung und nachfolgender Ro ntgenbestrahlung. Strahlentherapie 1915;6:205218.
25. Abe M. History of intraoperative radiation therapy. In:
Dobelbower RR, Abe M, editors. Intraoperative Radiation
Therapy. Boca Raton, (FL): CRC Press; 1989.
26. Barth G. Erfahrungen und Ergebnisse mit der Nahbestrahlung operativ freigelegten Tumoren. Strahlentherapie
1953;91: 481527.
27. Goin LS, Hoffman EF. The use of intravesical low voltage
contact Roentgen irradiation in cancer of the bladder. Radiology 1941;37:545.
28. Biggs PJ, Noyes CG, Willett CG. Clinical physics, applicator
choice, technique and equipment for electron intraoperative
radiation therapy. In: Petrelli N, Merrick III HW, Thomas Jr
CR, editors. Surgical clinics of North America. Philadelphia,
PA: W.B. Saunders; 2003.
29. Hensley FW, Ciocca M, Petrucci A, Biggs PJ. Survey of IORT
activities in Europe. IVth International meeting of the International Society of Intraoperative Radiation Therapy. Miami,
(FL): Mar 1719, 2005.
30. Schultz MD. The supervoltage story. Amer J Roentgenol Rad
Therapy Nucl Med 1975;124:541559.
31. Henschke G, Henschke U. Zur Technik der Operationsbestrahlung. Strahlentherapie 1944;74:228239.
32. Eloesser L. The treatment of some abdominal cancers by
irradiation through the open abdomen combined with cautery excision. Ann Surg 1937;106:645652.
33. Fairchild GC, Shorter A. Irradiation of gastric cancer. Br J
Radiol 1947;20:511.
34. Podgorsak E, Metcalfe P, Van Dyk J. Medical Accelerators.
In: Van Dyck J, editor. The modern technology of radiation
oncologya compendium for medical physicists and radiation oncologists. Madison, (WI): Medical Physics Publishing;
1999.
35. Mills MD et al. Shielding consideration for an operating room
based intraoperative electron radiotherapy unit. Int J Radiat
Oncol Biol Phys 1990;18:12151221.
36. Meurk ML, Schonberg RG, Haynes G, Vaeth JM. The
development of a small, economic mobile unit for intraoperative electron beam therapy. Am J Clin Oncol 1993;16:
459464.
37. Mills MD et al. Commissioning of a mobile electron accelerator for intraoperative radiotherapy. J App Clin Med Phys
2001;2: 121130.
29
38. Daves JL, Mills MD. Shielding assessment of a mobile electron accelerator for intraoperative radiotherapy. J Appl Clin
Med Phys 2001;2:165173.
39. Piermattei A et al. The saturation loss for plane parallel
ionization chambers at high dose per pulse values. Phys
Med Biol 2000;45:18691883.
40. Fantini M et al. IORT Novac7: A new linear accelerator for
electron beam therapy. In: Vaeth JM, editor. Intraoperative
radiation therapy in the treatment of cancer. Vol. 31. Front.
Radiation Therapy Oncology Basel: Karger; 1997.
41. Tosi G, Ciocca M. IORT with mobile linacs: The Italian
experience. Oncologia 2004;27:350354.
42. Hogstrom KR et al. Design of metallic electron beam cones for
an intraoperative therapy linear accelerator. Int J Radiat
Oncol Biol Phys 1990;18:12231232.
43. AAPM, American Association of Physicists in Medicine, Task
Group 25, Radiation Therapy Committee, Clinical electron
beam dosimetry, Report of AAPM radiation therapy committee Task Group 25. Med Phys 1991;18:73109.
44. Almond PR et al. AAPMs TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.
Med Phys 1999;26:18471870.
45. Kutcher GJ et al. Comprehensive QA for radiation oncology,
Report of AAPM Radiation Therapy Committee Task Group
40. Med Phys 1994;21:581618.
46. Davis MG, Nyerick CE, Horton JL, Hogstrom KR. Use of routine
quality assurance procedures to detect the loss of a linear
accelerator primary scattering foil. Med Phys 1996;23:521522.
47. Palta JR, et al. Intraoperative electron beam radiation therapy, technique, dosimetry, and dose specification, report of
Task Group 48 of the radiation therapy committee, American
Association of Physicists in Medicine. Int J Radiat Oncol Biol
Phys 1995;33:725746.
48. Beddar AS et al. Intraoperative radiation therapy using
mobile electron linear accelerators: Report of the AAPM Radiation Therapy Committee Task Group 72. To be published.
49. Hazle JD, Chu JCH, Kennedy P. Quality assurance for
intraoperative electron radiotherapy clinical trials: Ionization chamber and mailable thermoluminescent dosimeter
results. Int J Radiat Oncol Biol Phys 1992;24:559563.
50. Beatty J, et al. A new minature x-ray device for interstitial
radiosurgery: dosimetry. Med Phys 1996;23:5362.
51. Yanch JC, Harte KJ. Monte Carlo simulation of a minature
radiosurgery x-ray tube using the ITS 3.0 coupled electronphoton transport code. Med Phys 1996;23:15511558.
52. Beddar SA. Dose delivery for HDR-IORT using curved HAM
applicators. IVth International meeting of the International
Society of Intraoperative Radiation Therapy. Miami, (FL):
Mar 1719, 2005.
53. Raina S et al. Quantifying IOHDR brachytherapy underdosage resulting from an incomoplete scatter environment.
Int J Radiat Oncol Biol Phys 2005;61:15821586.
54. Harrison LB, Cohen AM, Enker WE. High-dose-rate intraoperative irradiation (HDR-IORT): Technical factors. In:
Gunderson LL, Willett CG, Harrison LB, Calvo FA, editors.
Intraoperative Irradiation: Techniques and results. Totowa,
(NJ): Humana Press; 1999.
55. Gunderson LL et al. Locally advanced primary colorectal
cancer: Intraoperative electron and external beam irradiation 5-FU. Int J Radiat Oncol Biol Phys 1997; 37:601614.
56. Gieschen HL et al. Electron or Orthovoltage IORT for retroperitoneal sarcomas. In: Gunderson LL, Willett CG, Harrison
LB, Calvo FA, editors. Intraoperative Irradiation: techniques
and results. Totowa, (NJ): Humana Press; 1999.
See also RADIOSURGERY, STEREOTACTIC; X-RAY THERAPY EQUIPMENT, LOW
AND MEDIUM ENERGY.
30
RADIOTHERAPY, THREE-DIMENSIONAL
CONFORMAL
GEORGE STARKSCHALL
The University of Texas
Austin, Texas
INTRODUCTION
The goal of radiation therapy is to deliver a sufficient dose of
radiation to a tumor site to control the disease while keeping
doses to uninvolved tissue within tolerable limits. In order to
achieve this goal, radiation beams are typically directed to
the tumor target from several directions. Consequently, multiple beams irradiate the target, but only a few beams irradiate the uninvolved tissue surrounding the target, thus
reducing the dose to the uninvolved tissue. The portals used
to define the radiation fields are carefully shaped to fit the
target in order to further reduce the amount of radiation reaching the tissue surrounding the target. In three-dimensional
conformal radiotherapy (3DCRT), the radiation dose distribution is designed to conform to the contours of a target volume.
The method by which the beam geometries and treatment
portals of 3DCRT are designed differentiates 3DCRT from
earlier methods of radiation treatment planning and delivery.
Prior to the 3DCRT era (mid-1990s), radiation treatment
planning was based on a small number of computed tomography (CT) images of the patient and radiographic images
from a simulator, a diagnostic X-ray machine whose geometries simulated the geometries of the radiation treatment
machine. Beam configurations were determined based on a
CT image of the patient in a single transverse plane, typically the plane containing the central axes of the radiation
beams. Treatment portals were determined from the simulation radiographs; the design of these portals was based
primarily on bony landmarks that were visible on the radiographs. Radiation doses were computed in the plane containing the beam central axes, and plans were evaluated on
the basis of information displayed in that plane (1).
With the development of fast CT scanners and fast treatment
planning computers with inexpensive memory, radiation therapy
moved into the 3DCRT era. Whereas in the past, radiation
treatments were planned and evaluated on the basis of information in a single or limited number of planes, radiation treatment
planning is now based on patient volume. Patient information is
acquired over a volume of the patient, treatment portals are
designed to irradiate a target volume, doses are calculated in
volumes of tissue, and treatment plans are evaluated based on
dosevolume considerations. The 3DCRT process currently used
in contemporary radiation therapy consists of the following
steps: (1) accurately imaging the tumor and normal tissue in
three dimensions, (2) precisely defining the target volumes,
(3) optimizing beam geometries and beam weights, (4)
translating the treatment plan to produce accurate delivery
of radiation according to the treatment plan, and (5) verifying the accuracy of the delivery of radiation.
IMAGING FOR RADIATION ONCOLOGY
In the current state of practice in 3DCRT, treatment
planning is based on virtual (CT) simulation. A 3D CT
the CT image data set and projected onto the DRR. Treatment portals are then designed based on the projected
contours. The design of a treatment portal based on the
volumetric extent of the tumor is a key component of the
3DCRT process. In addition, many soft-tissue anatomic
structures may also be difficult to visualize on a conven-
31
32
33
34
Treatment portals are determined for each beam geometry and designed to encompass the PTV along with a
margin to allow for the fact that the beam does not end
abruptly at the geometric edge but rather the dose distribution has a finite slope at the beam edge. Caused both
by the fact that the radiation source is not a point source
and that radiation can scatter from the irradiated region
to the blocked region, this penumbra requires that the
treatment portal surround the PTV with a margin of
from 0.5 to 1 cm in order to deliver a high dose to the
PTV. The treatment planning typically designs the treatment portal based on viewing the BEV projection of the
PTV on a DRR.
In addition to optimizing the beam geometries, the
planning often must also optimize the beam weights. Typically, this optimization consists of manual fine tuning of
the beam weights to deliver a more uniform dose across the
target volume, decrease the dose to specific critical structures, or both of these outcomes. However, if specific prescription goals are established, such as desired doses to
target volumes and maximum allowed doses to critical
structures, various computer algorithms can be used to
optimize the beam weights. If additional conformality of
the dose distribution to the target volume is desired, techniques exist for the planning and delivery of intensitymodulated radiation therapy (IMRT). This technique is
particularly useful if the target volume is concave.
DOSE CALCULATION
In most current radiation treatment planning systems,
X-ray dose distributions are calculated using a convolution
algorithm (6,7). In this algorithm, the radiation dose is
obtained by convolving an incident fluence distribution
with a dose-spread array. The dose-spread array represents the distribution of radiation dose around a point in
The 3DCRT can also be achieved using beams of chargedparticle radiation, such as electrons or protons. In some
respect, achieving 3DCRT is easier with charged-particle
beams than it is with X-ray beams. One feature that
differentiates the dose distribution from charged-particle
beams from that of X-ray beams is that the dose distribution from charged-particle beams, at least to a first approximation, is constant from the patient surface to a depth
equal to the range of the charged particle, and then goes
rapidly to zero. This distribution results from the charged
particles property of depositing a fixed amount of energy
per interaction until the particle energy is exhausted;
beyond that depth, no energy is deposited. Consequently,
the lateral extent of a charged-particle beam can be shaped
based on the BEV projection of the PTV, just as are X-ray
beams, but the depth of penetration of a charged-particle
beam can be made to track the distal surface of the PTV by
spatially modulating the energy of the beam, which shifts
the range of the charged particles. A simple method for
range-shifting involves placing a sufficient amount of
attenuating material in the path of the beam to reduce
the local energy of the beam so that its range is slightly
greater than the depth of the distal surface of the PTV.
Alternatively, one could modify the spatial distribution of
the energy of the beam by modifications in the beam
transport in the head of the particle accelerator.
Particle therapy, on the other hand, has some limitations. The margins of electron beam dose distributions are
not as sharp as those for X-ray beams because of multiple
scattering. In addition, heterogeneities and surface irregularities cause significant perturbations in the electron
beam dose distributions. Widespread use of proton beams
may be limited because of the significantly higher cost of
production of therapeutically useful beams.
RADIATION DELIVERY
Once a 3DCRT treatment plan has been developed, it is
necessary to translate the treatment plan accurately to the
VERIFICATION OF DELIVERY
The final step in 3DCRT is that of quality assurance,
verification that the radiation beams delivered to the
patient are consistent with those planned for delivery.
All components of the planning and delivery process need
to be reviewed as part of a quality assurance process,
including the validity of the treatment plan, the accuracy
of the machine settings, the validity of the transfer of data
from the planning system to the radiation machine, the
accuracy of the portal for delivery of the radiation beam,
the accuracy of the patient setup, and the accuracy of the
radiation delivery.
The first step in verification is that of verifying that the
treatment plan accurately reflects the radiation dose that
is actually designed to be delivered to the patient. This is
achieved by implementation of a quality assurance program for the treatment planning system. In such a program, one verifies that the treatment-planning system
accurately depicts the patient images, contours, and beams
that are provided as input into the dose calculations, and
that the beam models are accurate, so that the doses
calculated by the treatment planning system are accurate
(9).
The next component of verification is that the machine
setting determined by the treatment-planning system will
deliver the correct dose to the target. Accuracy of machine
setting is verified initially when the beam model is first
commissioned and introduced into the treatment-planning
system and is verified for each dose calculation by and
independent calculation of radiation doses to individual
points within the patient.
Next, it is necessary to verify that the machine settings,
such as beam geometries, and monitor units are accurately
transferred from the treatment-planning system to the
machine. In many radiation oncology clinics, a record
and verify (R&V) system is used to record the machine
settings used to deliver the radiation beams to the patient,
ensuring that machine settings lie within clinically
accepted tolerances of the values established on the treatment plan. A component of a comprehensive quality assurance program verifies that the machine settings
determined by the treatment-planning system are accurately transferred into the R&V system.
Another key step is to verify that the treatment field
actually delivered to the patient is identical to the treatment portal as determined on the treatment plan. In order
to accomplish this task, a radiographic image of the delivered treatment portal is acquired. The portal image is then
compared to a DRR of the treatment field extracted from
35
36
Figure 6. A DRR of an anterior pelvic treatment field compared with a portal image of the same
field used to verify that the patient is set up accurately and that the location and extent of the
irradiated region is as per plan.
37
CONCLUSIONS
Figure 8. Sagittal ultrasound images of a patient before and after realignment of the patient.
(Figure courtesy of Lei Dong, Ph.D., U. T. M. D. Anderson Cancer Center.)
38
BIOLIOGRAPHY
1. Starkschall G. What is 3-D radiotherapy treatment planning.
In: Purdy JA, Starkschall G, editors. A Practical Guide to 3-D
Planning and Conformal Radiation Therapy. Madison, WI:
Advanced Medical Publishing; 1999. p 116.
2. Bushberg JT, Seibert JA, Leidholdt EM, Boone JM. The
Essential Physics of Medical Imaging. Philadelphia, PA:
Lippincott Williams & Wilkins; 2003. Chapt. 13.
3. Goitein M, Abrams M, Rowell D, et al. Multi-dimensional
treatment planning: II Beams eye-view, back projection, and
projection through CT sections. Int J Radiat Oncol Biol Phys
1983;9:789797.
4. International Commission on Radiation Units and Measurements (ICRU) Report 50: Prescribing, Recording, and Reporting Photon Beam Therapy. ICRU (1993) Bethesda MD.
5. International Commission on Radiation Units and Measurements (ICRU) Report 62: Prescribing, Recording, and
Reporting Photon Beam Therapy (Supplement to ICRU
Report 50). ICRU (1999) Bethesda MD.
6. Mackie TR, Scrimger JW, Battista JJ. A convolution method of
calculating dose for 15 MV x-rays. Med Phys 1985;12:188196.
7. Boyer AL, Mok EC. A photon dose distribution employing
convolution calculations. Med Phys 1985;12:169177.
8. Ma CM, Mok EC, Kapur A, Pawlicki T, Findley D, Brain S,
Forster K, Boyer AL. Clinical implementation of a Monte Carlo
treatment planning system. Med Phys 1999;26:21332143.
9. Fraass BA, Doppke KP, Hunt MA, et al. Task Group 53:
Quality assurance for clinical radiotherapy treatment planning. Med Phys 1998;25:17731829.
10. Kutcher GJ, Coia L, Gillin M, et al. Comprehensive QA for
radiation oncology: Report of AAPM Radiation Therapy Committee Task Group 40. Med Phys 1994;21:581618.
11. Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer
radiation dose response: Results of the M.D. Anderson phase
III randomized trial. Int J Radiat Oncol Biol Phys 2002;53:
10971105.
Further Reading
Khan F. The Physics of Radiation Therapy. 3rd ed. Philadelphia,
PA: Lippincott Williams & Wilkins; 2003. especially Chapt. 19.
See also RADIATION
INTRODUCTION
Treatment of solid tumors typically involves some combination of surgery, chemotherapy, and radiation therapy.
With any of these approachesindeed, as with so much of
medicinethe objective is to eradicate or control the disease without producing unacceptable side effects. Radiation therapy, in particular, is used for one-half of all cancer
patients in the United States, and can frequently contribute to the cure of a malignant tumor, or at least to a
significant improvement in quality of life.
Intense localized irradiation of the region of a solid
tumor can both incapacitate or kill cancer cells directly,
and strangle them through damage to tumor-bed microvasculature. High doses of ionizing radiation will kill not
only the cells of tumors, however, but also those of healthy
tissues. So a successful treatment must target the tumor
accurately, with little radiation ending up elsewhere; it
would be of questionable benefit to eradicate a tumor of the
esophagus if this also led to severe functional complications
in the spinal cord.
Radiation therapy is therefore preceded by a careful,
and sometimes extensive, planning process, and a search
for a best treatment plan.
This article is based on material found in Ref. 1.
Stumor
Sorgan
S(D)
39
Spatient
0
Dopt
(1)
40
2.
3.
4.
5.
6.
41
42
43
J X
K
X
djk wk Dv
j
healthy tissue
3b
tumor
4a
Dl0 Dtolerance
K
X
djk wk
healthy tissue
4b
(2)
fID
3a
44
M
X
Dm Dav 2
(5)
6a
cD Dn=nDDD
6b
equivalently,
7a
7b
7c
8a
D=D0
(8b)
This can be rewritten in terms of the geometrical characteristics of the curve, namely D50 the dose resulting in
50% probability of complication, Sorgan 0.5 (see also Ref.
20), and slope, g50:
Stumor D e
(8c)
8d
45
J
Y
sD j
8e
One of the main characteristics of a tumor is its comparatively fast repopulation rate. To account for this in conjunction with the Poisson (or binomial) distribution,
several authors in the 1980s proposed setting the initial
number of clonogens to n(0), after which n(t) n(0)elt,
where l and t are the rate constant and repopulation time,
respectively (2326). This approach predicts a Stumor(t)
that always tends to zero for large post-treatment times,
which is incorrect. Later, taking clonogen repopulation
between fractions (2730) into account lead to the ZaiderMinerbo model (31) of Stumor(t), which is applicable
for any temporal treatment protocol. An expression for
Stumor(t) with different time intervals between consecutive
irradiation fractions and with varying cell survival probability per fraction was obtained by Stavreva et al. (32)
based on the ZaiderMinerbo approach. Animal experiments support the validity of the ZaiderMinerbo approach
(32).
Other approaches to the determination of Stumor are
discussed in the literature (3336).
Integral Response for a Healthy Organ
Several ways have been devised to address the non-uniform irradiation of healthy tissues. One of these is an
extension of the integral dose idea, introduced in equations
3 and 4. It does not focus on the spatially varying dose
distribution within a tissue per se, as do the physical
geometric approaches, but rather on the local biological
response that the dose elicits. Variation on the approach, of
a range of levels of complexity, have been discussed by a
number of researchers (18,3741).
Imagine an organ or biological compartment that produces some physiologically important substance (such as a
critical enzyme or hormone) or that performs an important
task (like phagocytosis or gas exchange). If too many of its
cells are inactivated by irradiation, then the organ cannot
do its job adequately, and the organism runs into trouble.
As before, mathematically partition the organ into J small
volume elements of size Dv, and assume that the radiation
response of any such voxel (or of the cells within it) is nearly
independent of its neighbors response. If, moreover, high
LET radiation is again involved, the doseresponse relationship is of the form of equation 7b, where D0 contains all
the important biophysics.
Of the entire organ, only the fraction
v 1=J Dv
J
X
eD j =D0 Dv
9a
46
v reduces to the
9c
Q
Y
Sorgan q
9d
Automated treatment plan optimization may then be carried out, in principle, with a combination of equations 2, 4,
and 9.
Another possible method of handling non-uniform irradiation of such an organ is based on its N-step dosevolume
histogram. The idea is to reduce it in such a fashion as to
yield a revised histogram that corresponds to the same
complication probability, but that contains only an (N 1)
steps; this calculation is repeated (N 1) times, until there
is left a single-step histogram, the Sorgan of which can be
obtained from experiment or clinical observation.
Several algorithms have been proposed for carrying out
the histogram-reduction process (4247).
Healthy Organ Composed of Separately Critical Voxels
The integral response objective function is based on the
effectiveness of operation of a healthy organ taken as a unit
(48). A radically different approach is needed for an organ,
such as the spinal cord or certain regions of the brain, that
behaves like a chain or computer program, in which serious
complications in any single small part can spell disaster for
the whole.
Once again, consider an organ made up of J radiobiologically independent voxels. Let s(Dj) refer to the probability that the organ will suffer no serious complications
when the jth voxel is taken to dose level Dj and the rest is
left unirradiated. If the entire organ is to escape damage,
each of its J parts must do so separately, and
Sorgan
J
Y
sD j
Sorgan sDJ
9b
10a
10b
CONCLUSION
The radiation response of a tissue depends in an extremely
complex way on a number of parameters, some of which the
radiation oncologist can control directly, some indirectly,
and some not at all. One can choose the modality (X rays,
electrons, gamma-rays, protons, neutrons); the volume to
be irradiated; the dose per fraction and number of fractions; the administration of response-modifying drugs; and
the spatial dose distribution in healthy tissues. Some of the
generally uncontrollable (or weakly controllable) parameters are radiosensitivity differences of different constituent parts of a tissue; tissue concentrations of oxygen,
drugs, toxins, and other compounds; numbers of cells in
each portion of the mitotic cycle; differential cell population
kinetics; and repair of radiation-induced cellular injury.
Manipulation of directly controllable variables may lead to
changes in others: reoxygenation; differential cell cycle
phase redistribution; differential recruitment of proliferative cells; and differential repair.
In view of this complexity, it is not clear how effective
empirical or ab initio mathematical modeling can be in
providing clinically useful descriptions of processes as
intricate as the kinetics of irradiated tissues. At the present time, the subject is largely of academic interest. But
itis to be expected that over the next several decades,
computer-based expert systems will continue to spread
throughout all of medicine. This development, together
with the increasing automation of radiation delivery systems, will doubtless cause the search for quantitative
methods of treatment plan optimization to expand.
BIBLIOGRAPHY
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3. Jackson A, Ten Haken RK, Robertson JM, Kessler ML,
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47
25. van de Geijn J. Incorporating the time factor into the linearquadratic model. Br J Radiol 1989;62:296298.
26. Yaes RJ. Linear-quadratic model isoeffect relations for proliferating tumor-cells for treatment with multiple fractions
per day. Int J Radiat Oncol Biol Phys 1989;17:901905.
27. Tucker SL, Thames HD, Taylor JM. How well is the probability of tumor cure after fractionated irradiation described
by Poisson statistics? Radiat Res 1990;124:273282.
28. Yakovlev AY. Comments on the distribution of clonogens in
irradiated tumors. Radiat Res 1993;134:117120.
29. Kendal WS. A closed-form description of tumour control with
fractionated radiotherapy and repopulation. Int J Radiat
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34. Roberts SA, Hendry JH. A realistic closed-form radiobiological
model of clinical tumor-control data incorporating intertumor
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35. Fenwick JD. Predicting the radiation control probability of
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Biol 1998;43:21592178.
36. Brenner DJ. Dose, volume, and tumor-control predictions in
radiotherapy. Int J Radiat Oncol Biol Phys 1993;26:171179.
37. Kallman P, Agren A, Brahme A. Tumour and normal tissue
responses to fractionated non-uniform dose delivery. Int J
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38. Withers HR, Taylor JM, Maciejewski B. Treatment volume
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39. Jackson A, Kutcher GJ, Yorke ED. Probability of radiationinduced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med Phys 1993;
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40. Niemierko A, Goitein M. Modeling of normal tissue response
to radiation: The critical volume model. Int J Radiat Oncol
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41. Olsen DR, Kambestad BK, Kristoffersen DT. Calculation of
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44. Kutcher GJ, Burman C. Calculation of complication probability factors for non-uniform normal tissue irradiation: The
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45. Kutcher GJ, Burman C, Brewster L, Goitein M, Mohan R.
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46. Niemierko A, Goitein M. Calculation of normal tissue complication probability and dose-volume histogram reduction
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Lyman JT. Complication probability as assessed from dosevolume histograms. Radiat Res (Suppl) 1985;8:S13S19.
Yaes RJ, Kalend A. Local stem cell depletion model for
radiation myelitis. Int J Radiat Oncol Biol Phys 1988;14:
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Stavrev P, Stavreva N, Niemierko A, Goitein M. Generalization of a model of tissue response to radiation based on the
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damage to contiguous functional subunits. Int J Radiat Biol
2001;77:695702.
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HERMAN VERMARIEN
Vrije Universiteit Brussel
Brussels, Belgium
INTRODUCTION
Graphic recorders, as considered here, are essentially
measuring instruments that produce in real-time graphic
representations of biomedical signals, in the form of a
permanent document intended for visual inspection.
Recorded data are thus fixed on a two-dimensional (2D)
medium which can simply be called paper (although the
material applied may differ from ordinary writing paper);
A so-called hard copy of the information is generated.
Equivalent names are paper recorder, direct writing recorder, plotter, chart recorder, and strip chart recorder (if long
strips of paper are used); In some cases, the more general
term hard-copy unit is also applied. The nomenclature
oscillograph is sometimes used (in correspondence with
the other display instrument, the oscilloscope). By the
aspect of visual inspection the graphic recorder is distinguished from other data storage devices (e.g., magnetic or
optical disk, solid-state memory), whereas in the property
of permanence graphic recording differs from visual monitoring as realized by the oscilloscope or the computer
screen. Real-time paper recordings have the benefit of
direct visual access to signal information, allow immediate
examination (and re-examination) of trends (as long strips
of paper can be used), present better graphic quality than
RECORDERS, GRAPHIC
49
Depending on the transducing device applied, two categories of recorders can be considered: analog and digital. In
analog recorders, a physical displacement occurs: Positioning (y) of the pen (or ink jet, light beam or other), toward the
site on the paper to be marked. In digital recorders, as
50
RECORDERS, GRAPHIC
Figure 1. Time signals and graphic representation. On the left, two time signal examples are given:
ECG (bipolar lead II) and aortic blood pressure. On the right, the ty recording is sketched as
executed by galvanometric rectilinear pen-writing devices on calibrated paper. For ECG and blood
pressure the recording sensitivities have to be known. This is accomplished by recording a
calibration pulse: 1 mV for ECG, 100 mmHg (0.133 kPa) for pressure. For pressure the zero level
is obviously necessary. The time effect is generated by pulling a paper supplied from a paper roll over
the writing table. Remark: Nowadays these types of signals are mostly recorded with a digital
recorder (thermal array) or a PC application.
RECORDERS, GRAPHIC
51
52
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53
parameters (sensitivities, reference levels, time references, paper velocity) are, as already indicated in relation
to accuracy, best reported in the form of calibration lines.
Alphanumeric information for identification of signals
and calibration lines, on the one hand, and data concerning the circumstances of the experiment (patient or subject name, date, experiment identification, stimulus type,
etc.), on the other hand, are indispensable for off-line examination. They either must be manually added to the record
or, preferably, must be added through the recorder itself.
Digitally controlled recorders (using digital as well as analog
transducers) may allow the operator to introduce the alphanumeric data together with tracings, provided the device is
able to do it. In the case of digital transducers this is only a
matter of appropriate hardware and software (to be supplied
in the recorder) and/or interfacing with a computer.
Whereas in digital transducers recording is essentially
based on intensity control, in analog transducers this aspect
is not necessarily provided.
Reading stored paper tracings by using waveform tracing techniques in order to be able to process data in digital
format may be interesting for a number of studies. Nevertheless, attention has to be paid to the recording accuracy
of older tracings and the experimental procedures used.
Graphic Quality
As mentioned in the introduction, the second of the two
principal recording properties is the quality of graphics.
The correctness of locating the point to be marked is part of
the performance of a measuring instrument. In this section, the quality of the apparatus in producing a graphic
hard copy is discussed. The clearness of the individual
tracings is the first quality. Sharp and clean tracings on
a bright background give the best impression. Vague or
blurred lines and dirty background are not wanted.
Furthermore, curves should be easily identified: Ease
and speed in examination are thus improved and the risk
of misinterpretation is considerably decreased. Although
the use of different colors seems most appropriate, other
techniques may be applied if color differences are technologically excluded, for example, writing intensity (gray
scale) or even line thickness. Also, the impression of continuous lines can assist in curve examination; Adequate
interpolation between sample points is thus a specific
problem to be handled in the case of digital and discontinuous analog recorders (Fig. 2).
In the graphic process, two steps are involved. First,
the act of writing (putting a visual mark on the paper at the
located point). Second, the act of fixation (to maintain
the mark for a long time). This evidently has to do with
the aspects of visual inspection and permanence in the
definition of graphic recorders. Graphic quality also relates
to the aspect of permanence. For example, depending on the
fixation process, photographic records may be affected by
environmental light in the form of a darkened background.
Attention should be paid to the fact that the flow of
marking matter (ink, heat, light, etc.) is to be adapted to
the writing velocity in order to have optimal line thickness
and grayness. In analog transducers the writing velocity
is determined by the paper velocity (in the x direction) and
54
RECORDERS, GRAPHIC
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overlapping graphs). In this case, a pen offset compensation may be used to synchronize recorded tracings, also
causing a time delay.
In this Paragraph a number of technological aspects
were just mentioned. Some of these concepts have lost
interest with respect to new design, but may still be found
in older apparatus.
ANALOG RECORDERS
An analog recorder has been defined as a recorder that
applies an analog electromechanical transducing principle.
The electrical magnitude is transduced into a translational
value, that is, positioning of a movable part, such as a pen,
toward the site to be marked. Although analog recorders
are used mostly for signals in analog form, they may also be
applied to digital signals and consequently to computer
output, provided digital-to-analog conversion facilities and
appropriate control access (paper velocity, intensity control) are available.
For the description of the transducer, analog system
theory is applicable (13). Two typical measurement principles are commonly used in transducer design. In the
direct method, the electrical magnitude is directly transduced into a displacement magnitude. In the feedback
method, corresponding to the null detection technique,
the actual position of the marking device is measured with
an accurate sensor. The difference (the error) between
the measured and the input value is, after appropriate
conditioning, fed back to the transducer, which generates a
movement tending to zero the position error. In the latter
case, the accuracy of the transducing system depends on
the quality of the position sensor. It is known that with this
method higher accuracies and more stable transducing
properties can be achieved. Furthermore, an analog transducer can be applied in the continuous mode or the discontinuous mode. In the first case, a single continuous
tracing is generated by each transducer; The number of
channels is equal to the number of transducers provided in
the multichannel recorder. Production of an image is
excluded. In the second case, the writing device is repeatedly swept over the complete paper width, setting dots or
dashes at sites corresponding to the signal values (the
scanning mode). A single transducer can thus handle a
set of signals. It is obvious that what is gained by the ability
to process different signals is lost with respect to the
writing speed of the system.
Positioning of the writing device can be caused by
a transducer that causes a rotation (the galvanometric
transducer) or a translation (the translational servosystem). The translational servotransducer evidently makes
use of a feedback mechanism. The galvanometric transducer, originally strictly built as a direct device, has also
been designed according to the feedback principle.
Whereas two decades ago a number of analog transducer
techniques were applied in apparatus design for biomedical
signal recording, mostly for obtaining different bandwidths
and image recordings (as for echocardiography), only a few of
them are still used. The galvanometric recorder and, more
importantly, the translational servorecorder.
55
Galvanometric Recorders
Galvanometric recorders make use of transducers that are
essentially rotational transducers, making use of the
dArsonval movement as applied in ordinary galvanometers (4). A positioning, more specifically a rotation over
a certain angle, is obtained as a result of an equilibrium
between two torques, the first an electromagnetic torque,
proportional to current, the second a mechanical torque,
proportional to positioning (a rotation angle). A coil wound
in a rectangular form is suspended within the air gap
between the two poles of a permanent magnet and a
stationary iron core. A current flowing through the coil
gives rise to an electromagnetic torque that tends to rotate
the coil. To position at a specific angle u, there must be a
restoring torque, essentially proportional to the angle, for
example, a torsional spring characterized by its rotational
stiffness. The signal to be recorded is fed to a current
amplifier that drives the coil. As such, there is direct
proportionality between the angle and the signal. This
principle corresponds to the direct transducing method.
In a discussion of dynamic behavior, not only stiffness,
but also damping (viscous friction) and inertial moment (of
the coil and the attached mechanical parts, e.g., the pen)
must be taken into account. As a first approximation the
device acts as a second-order linear system, characterized
by a resonant frequency and a damping factor. The resonant frequency depends on the ratio of stiffness divided by
inertia. The resonant frequency and the damping factor
determine the bandwidth of the system (with respect to
sine wave response) and the time delay, rise time, and
overshoot (with respect to step input transient response).
For frequencies sufficiently above the resonant frequency,
the corresponding amplitudes are attenuated proportional
to the square of the frequency. A second-order system can
show resonant phenomena, depending on the value of the
damping factor. If this factor is <1, the response of the
transducer to a step input shows a ringing effect, implying
that an overshoot exceeding the steady-state value has
occurred. The smaller the damping, the smaller the rise
time, but the higher the overshoot. At critical damping
(damping factor 1) no overshoot is present. Such an
overshoot is considered inconvenient as it gives an erroneous impression of the waveform (especially if sudden
alterations in the signal occur). With the damping factor in
the proximity of 0.7 a good compromise is obtained between
the overshoot (4%) and the rise time (3) (Fig. 3). The useful
bandwidth of the recorder is thus determined by the resonant frequency and thus by the ratio of stiffness to inertia.
To obtain a sufficient damping factor, extra damping must
be applied within the galvanometer (mechanical or electromagnetic). In the case of paper-contacting devices, the
damping should exceed the effect of the static friction of the
writing element (e.g., the pen) on the paper (as this effect is
unreliable and consequently is not allowed to affect the
measuring performance).
The feedback technique has also been used. According
to the general idea, the actual angle is measured by a
position-sensing device, delivering an output proportional
to the angle, which, after amplification and waveform
conditioning, is negatively fed back to the input of the
56
RECORDERS, GRAPHIC
RECORDERS, GRAPHIC
57
Pen
Writing
table
Paper
roll
(a)
(b)
D
y
R
Pen
Knife edge
Paper roll
R2
Pen
R1
d1
d2
the instrument is started, a significant amount of thermosensitive paper may be wasted. Instead of a hot stylus, a
carbon ribbon with an ordinary stylus pressing on it has
been used. In this case, ordinary paper can be used, but an
additional mechanical device linked with the paper velocity
equipment for driving the carbon ribbon is necessary.
Rectilinear recordings can also be generated via mechanical linkages that compensate for the normal curvilinear
movement of the pen and convert the rotary motion of the
coil into an (approximately) straight-line motion of the pen
tip. In the case of ink jet recorders, the writing device does
not make physical contact with the paper. In this case, a
fine ink jet is produced by pumping ink through a nozzle
connected to and thus rotated by the galvanometer toward
Writing
table
58
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RECORDERS, GRAPHIC
Thermal array
Paper
Paper drive
Paper roll
Thermal array
(bottom view)
59
interval) and on the paper speed. Signals are thus reproduced as discrete values at discrete times. Analog as well as
digital signals can be processed. In the analog case, sampling and digitization are part of the recording process.
At present, the borderline between digital graphic recorders, digital oscilloscopes, and data-acquisition systems
becomes unclear as a number of the latter instruments
are also provided with graphic recording facilities with
strip charts. Some digital recorder designs primarily focus
on fast acquisition of data and storage in memory for
reproduction afterward. These are indicated as memory
recorders and generally their real-time properties do not
match the fast graphical recording types. Digital graphic
recorders have a number of properties regarding dataacquisition, monitoring, storage, and communication with
computers.
The act of writing of the digital recorder is generally
thermal on thermosensitive paper. Also, an electrostatic
method has been used. The writing transducer is essentially a rectilinear array of equidistal writing points covering the total width of the paper. These writing styli consist
of miniature electrical resistances that are activated, that
is heated, by a current pulse of short duration. Typical
resolutions are 8 or 12 dots
mm1 according to the y direction. Static linearity of the recorder thus depends on the
quality of the construction of the array. Inconveniences
resulting from mechanical moving parts are not present.
There is no overshoot. Delay and rise time are equal to one
writing interval. All processing occurs in digital form and
recording is a matter of generating the correct addresses of
writing points to be activated.
Evidently, the dynamic thermal properties of the resistances in close contact with the chart paper and the shape
of the electric current pulse set a limit to the writing
frequency. A typical value for the writing frequency is
1.6 kHz. In a memory recorder, it may be lower. Local
heating of the thermosensitive paper results in a black
dot with a good long-term stability, dependent on the paper
quality. Evidently, thermal paper is sensitive to heat, but
also care has to be taken with pressure, light, solvents,
glue, and so on, in order to prevent detoriation of the
graph. Generally, the heating pulse is controlled with
respect to chart velocity in order to obtain an appropriate
blackness and line thickness at different velocities. Nevertheless, at the highest velocities the print may become less
black and sharp. Although possible within a limited range,
blackness and thickness of tracings are seldom used for the
purpose of trace identification.
Whereas the resolution according to the y axis is determined by the thermal dot array, the x-resolution is limited
by the dynamic properties of the array, and thus by the
paper velocity. At low velocities, generally 32 dots
mm1
(exceptionally 64 dots
mm1) are applied. At the highest
velocities used (100 mm
s1, in some apparatus 200 and
500 mm
s1), the number of dots printed is determined by
the writing frequency (e.g., 1600 Hz results in 8 dots
mm1
at 200 mm
s1).
Data acquisition is determined by the sampling frequency, expressed per channel recorded. According to
the sampling theorema this should be at least twice the
highest signal frequency in order to prevent aliasing
60
RECORDERS, GRAPHIC
memory media. Signals can thus be reproduced from memory, processed and recorded on chart. Time compression or
expansion is obviously possible. As data can be sampled at
a high rate, stored in memory, and then recorded as they
are released at a reduced rate, a bandwidth higher than
that determined by the writing frequency can be achieved.
In this way, fast transients that cannot be handled on-line
can be accurately reproduced. Data capture and/or graphic
recording (with an appropriate speed) can be controlled by
trigger functions (external or derived from recorded signals); Pre- and posttrigger may be chosen. Via memory xy
plots can be obtained. When appropriate software is available, FFT plots can be made.
Digital recorders can have analog and logic channels.
Typical numbers of analog channels are 4, 8, 16 (and
exceptionally 32 and 64). General monopolar or differential
amplifiers or signal conditioners with analog antialiasing
filters can be plugged-in, as well as special purpose amplifiers for biomedical purposes. Furthermore interfaces can
be provided for computer connection (RS-232C, IEEE-488,
GPIB, Ethernet, USB, SCSI) or external hardware. Software can be provided for control, data transfer and conversion of data to formats for popular data analysis
software programs.
EVALUATION
Table 1 shows a list of manufacturers of recorders, website
addresses and typical products. Analogue recorders with a
rotating pen arm, analog recorders with a translating pen
and digital thermal array recorders. Evidently, the list is
incomplete and continuously changing. For extensive practical details on recorders, signal conditioning modules,
displays, data storage and processing, computer interfacing, and so on, the manufacturers data sheets should be
consulted.
Analog recorders are characterized by their specific
technological limitations: the bandwidth, restricted mostly
by the inertia of the moving parts, imposing constraints on
the frequency content of the signal; the paper width covered by a trace, the number of channels, and the trace
overlap (including pen dislocation); the stability of the
recording parameters (including shifting of calibrated
paper) and the difficulties of adding coordinate lines and
alphanumeric identification to the records. The use of
auxiliary devices (timing marker, printing head, pen position compensation, etc.) has been shown to overcome some
of the limitations. The bandwidth is considered one of
the most important limitations and thus the signals
spectral content determines the choice of the recorder
type. Galvanometric pen recorder types (100 Hz bandwidth) have lost interest but some types can still be
purchased. A number of mechanisms have been applied
in commercially available devices, but in many applications analog types have been replaced by digital types or
PC set-ups. Translational servorecorders have kept their
position in their specific domain; They can be used for
slowly varying signals with a signal spectrum up to 5 Hz
(body temperature, heart rate, mean blood pressure,
laboratory applications, etc.).
RECORDERS, GRAPHIC
61
Rotating Pen
Translating Pen
Astro-Med, Inc.
http://www.astromed.com
Model 7 (ink)
WR3310 (tp)
WR7200 (tp)
WX3000/
WX4000 (dig)
(xy/ty)
R-60
Dash 18
Dash 2EZ
Dash 8X
Everest
Thermal Array
WR300
WR1000
WR8500
DMS1000
TA11
TA240
TA6000
WindoGraf
3057
LR4100E/
LR4200E/
LR8100E/
LR12000E (dig)
3023/3024 (xy/ty)
3025 (xy/ty)
OR100E/
OR300E
DL708E/
DL716 (ds)
DL750 (ds)
8826 (m)
8835-01 (m)
8841 (m)
8842 (m)
Kipp&Zonen
http://www.kippzonen.com
BD11/12
SE 102/122
SE 110/111/112
SE 124
BD300 (dig)
SE790 (xy/ty)
SE 520/540
SE 570
Soltec
http://www.solteccorp.com
MCR 560
DCR 520 (dig)
DCR 540 (dig)
TA200-938
TA200-3304
TA220-1200
TA2203216/3208
TA220-3424
TA220-3608
142
156
555/585/595
640
RD45A/46A
RD1101
RD1201/1202
RD2000
RD3720 (dig)
RD6100
RD6110
RD6112
600A (xy/ty)
790/791(xy/ty)
RD3020 (xy/ty)
Linseis
http://www.linseis.net
L120/200/250
L6514II
L7005II
LY14100II (xy/ty)
LY15100II (xy/ty)
Recorders with analogue transducers with rotating pen and with translating pen (servo) and recorders with digital transducer (thermal dot array). ink: inkpen;
tp: thermal pen; ds: digitals scope with chart recorder; m: memory recorder; xy: xy recorder; xy/ty: xy and ty recorder; dig: digital signal processing.
62
BIBLIOGRAPHY
1. Olsen WH. Basic concepts in instrumentation. In: Webster
JG, editor. Medical Instrumentation: Application and Design.
3rd edition. New York: John Wiley & Sons; 1998. p 143.
2. Bentley JP. Principles of measurement systems. 3rd ed.
Longman House: Longman Group Limited; 1995.
3. Sydenham PH. Static and dynamic characteristics of instrumentation. In: Webster JG, editor. The Measurement, Instrumentation and Sensors Handbook. Boca Raton (FL): CRC
Press; 1999. p 3/13/22.
4. Miller A et al., editors. Electronic Measurements and
Instrumentation. New York: Mc Graw-Hill; 1975. p 427479.
5. Bell DA. Electronic Instrumentation and Measurements.
2nd ed. Englewood Cliffs (NJ): Prentice-Hall; 1994.
See also ELECTROCARDIOGRAPHY, COMPUTERS IN; ELECTROENCEPHALOGRAPHY; ELECTROMYOGRAPHY; PHONOCARDIOGRAPHY.
INTRODUCTION
There is a growing need in clinical medicine to validate the
quantitative outcomes of an applied therapy. In addition,
the measurement of muscle function is an essential component of many neurological and physical exams. Muscle
strength is correlated to function, work productivity, and
general quality of life. Muscle function becomes compromised: (1) as we age, (2) when associated with a skeletal
impairment, and/or (3) as a secondary consequence of
many disease processes. Therefore, assessing muscle function is an important clinical skill that is routinely used by
neurologists, orthopedists, general practitioners, anesthesiologists, and occupational and physical therapists. Evaluation of muscle strength is used for differential diagnosis,
to determine if an impairment or disability is present, to
decide if a patient qualifies for treatment, and or to track
the effectiveness of a treatment.
In a research setting, the measurement of muscle function is used to further our understanding of the normal and
potentially impaired neuromuscular system in human and/
or animal experiments. In such research, muscle function
can be assessed at the intact individual level (in vivo), in
chronic and acute animal models (in situ), within isolated
63
64
Description
No palpable or observable muscle contraction
Palpable or observable contraction, but no motion
Moves limb without gravity loading less than one-half
available ROMb
Moves without gravity loading more than one-half ROMb
Moves without gravity loading over the full ROMb
Moves against gravity less than one-half ROMb
Moves against gravity greater than one-half ROMb
Moves against gravity less over the full ROMb
Moves against gravity and moderate resistance less
than one-half ROMb
Moves against gravity and moderate resistance
more than one-half ROMb
Moves against gravity and moderate resistance
over the full ROMb
Moves against gravity and maximal resistance
over the full ROMb
The simplest and most common method of assessing muscle strength is the manual muscle test (MMT). Manual
muscle testing is a procedure for evaluating strength and
function of an individual muscle or a muscle group in which
the patient voluntarily contracts the muscle against gravity load or manual resistance (2,7). It is quick, efficient, and
easy to learn, however, it requires total cooperation from
the patient and learned response levels by the assessor.
The procedures for conducting the MMT have been
standardized to assure, as much as possible, that results
from the test will be reliable (2,7,8). The specific muscle or
muscle group must be determined and the examiner must
be aware of, and control for, common substitution patterns
where the patient voluntarily or involuntarily uses a different muscle to compensate for a weak muscle being
tested.
To conduct a MMT, the patient is positioned in a posture
appropriate for the muscle being tested, which generally
entails isolating the muscle and positioning so that the
muscle works against gravity (Fig. 3). The body part proximal to the joint acted on by the muscle is stabilized. A
screening test is performed by asking the patient to move
the body part through the full available range of motion
Description
Maintains position against
Maintains position against
resistance
Maintains position against
moderate resistance
Maintains position against
resistance
Maintains position against
resistance
gravity
gravity and minimal
gravity and less than
gravity and moderate
gravity and maximal
65
66
67
Active Element
u
IRC
Activation dynamics
(2nd order)
CE force-length
CE force-velocity
Force
Fscale
Passive element
PE force-length
PE force-velocity
68
Torque
plate
Stabilizing
frame
Computer
Stimulator
amplifier
Unit
69
Unitsa
Definition
Peak torque
Contraction time
Half-relaxation time
Peak rate of development
Peak rate of decay
Time to peak development
Time to peak decay
Half-maximal duration
Latency to onset
N
m
s
s
N
m/s
N
m/s
s
s
s
s
N
m newton meters.
70
INTRODUCTION
The aim of this chapter is to provide an overview of current
issues involving the use of computers in cognitive rehabilitation. The chapter begins with a brief historical review of
computer use with a variety of disabilities including brain
injury, learning disability, psychiatric disorders, and dementias. It continues to address selected research findings on
the use of virtual reality for rehabilitation of impairments
in attention, memory, and functional daily living activities.
Finally, the chapter ends with conclusions and ethical reflections on using computers in research and direct care practice.
Impairments in cognitive function frequently occur as a
result of acquired brain injury (i.e., trauma, cerebrovascular
71
72
73
74
75
76
77
Figure 1. Examples of virtual reality environments. Image of the IREXTM system used with permission of GestureTek IncTM - World Leaders in Gesture Recognition Technology www. gesturetek.com.
78
BIBLIOGRAPHY
1. Cicerone KD, Dahlberg C, Kalmar K, Langenbahn DM, Malec
JF, Berquist TF, Felicetti T, Giacino JT, Harley JP, Harrington DE, Herzog J, Kneipp S, Laatsch L, Morse PA. Evidencebased cognitive rehabilitation: Recommendations for clinical
practice. Arch Phys Med Rehabil 2000;81:15961615.
2. Giaquinto S, Fioro M. THINKable, a computerized cognitive
remediation: First results. Acta Neurol (Napoli) 1992;14(46):547560.
3. Harley JP, Allen C, Braciszewski TL, Cicerone KD, Dahlberg
C, Evans S, Foto M, Gordon WA, Harrington D, Levin W,
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10. Glisky E, Schacter D. Long-term retention of computer learning by patients with memory disorders. Neuropsychologia
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16. MacArthur CA. Using technology to enhance the writing
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29. Ghosh A, Marks IM. Self-treatment of agoraphobia by exposure. Behav Ther 1987;18:316.
30. Wylie-Rosett J, Swenchionis C, Ginsberg M, Cimino C, Wassertheil-Smoller S, Caban A, Segal-Isaacson CJ, Martin T,
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31. Reitman R. The use of small computers in self-help sex
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32. McDaniel AM, Hutchison S, Casper GR, Ford RT, Stratton R,
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35. Weisman S. Computer games for the frail elderly. Gerontologist 1983;23(4):361363.
36. Schreiber M, Schweizer A, Lutz K, Kalveram KT, Jancke L.
Potential of an interactive computer-based training in the
rehabilitation of dementia: An initial study. Neuropsycholog
Rehab 1999;9(2):155167.
37. Gunther VK, Schafer P, Holzner BJ, Kemmler W. Long-term
improvements in cognitive performance through computerassisted cognitive training: A pilot study in a residential
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38. Hofmann M, Hock C, Kuhler A, Muller-Spahn F. Interactive
computer-based cognitive retraining in patients with Alzheimers disease. J Psychiat Res 1996;30(6):493501.
39. Hendrix C. Computer use among elderly people. Comput
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40. Mahendra N. Direct interventions for improving the performance of individuals with Alzheimers disease. Semin Speech
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41. Cho, Yang J, Kim SY, Yang DW, Park M, Chey J. The validity
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79
80
REHABILITATION, ORTHOTICS IN
REHABILITATION, ORTHOTICS IN
LOREN LATTA
University of Miami
Coral Gables, Florida
INTRODUCTION
Paralysis
Muscle weakness resulting from various forms of paralysis
is the major type of disability treated with orthotic devices.
Paralysis may be acute or chronic to varying degrees
depending on the state of the disease causing paralysis.
The degree of paralysis or paresis can change with time as
recovery is accomplished through therapy or healing of the
physiological cause. Thus, the orthotic need for support,
control of joint motion, and so forth, may change with time
for many of these patients. Orthotic devices in general are
designed for long-term use because many of the designs
were developed for chronic applications to polio patients in
the late 1940s and 1950s. With many new applications and
new materials, a variety of devices have been developed
that are ideal for short-term applications to more acute
conditions, for example, stroke, head injury, spinal cord
injury, and fractures.
Neuromuscular Control
Patients who suffer loss of neuromuscular control in the
form of spasticity, paralysis of isolated muscle groups, and/
or recovery of neuromuscular function resulting from
regeneration of neural tissue, which requires relearning
of coordination, are often helped with orthotic devices.
Although most of these applications are short term, a
few are chronic, such as in cerebral palsy, established
spinal cord injury, and head injury.
Deformity
Another common use of orthotics in a growing number of
cases is for musculoskeletal deformity. The first type of
deformity is related to mechanical instability of the limbs
or spine. Mechanical instability can result from soft tissue
or skeletal injury or from degenerative joint diseases that
cause chronic and progressive instability of the musculoskeletal system. One form of soft-tissue injury relating to
the instability of the skeleton is caused by surgical reconstruction of the joints. Therefore, many orthotic devices are
used for stabilization postoperatively when the spine or
upper or lower limb joints have been reconstructed. The
surgery often causes necessary damage to the stabilizing
soft-tissue structures that often adds to instability of prosthetic components that require bone healing for final stabilization. The second type of deformity is due to the growth
or remodeling disturbances in the skeleton. Orthotic applications are both acute and chronic in problems relating to
musculoskeletal deformity. Most chronic applications or
orthotics are in progressive deformities resulting from
degenerative joint diseases such as rheumatoid arthritis,
osteoarthritis, hemophilia, and diabetes. Orthoses generally are applied in these instances to prevent progressive
deformity and any resultant mechanical instability in the
Figure 1. (a) This KAFO is designed for chronic use. It has metal
uprights connected to metal bands covered with leather and padding
and a caliper type of stirrup that attaches to the shank of an
orthopedic shoe. All parts are custom fit from mostly prefabricated
components. (b) The other KAFO is designed for short-term use and
has a thermoplastic thigh and leg interface with the soft tissue,
connected to a plastic knee hinge suspended with a plastic posterior
shoe insert. All parts are prefabricated in standard sizes. Reprinted
with permission from Maramed Orthopaedic Systems.
REHABILITATION, ORTHOTICS IN
81
Figure 2. Splints that are used for short-term or long-term immobilization of joints are typically of
a simple design and can be prefabricated as in (a) WHOs (reprinted with permission from Maramed
Orthopaedic Systems) or custom fabricated as in (c) KAFO or (e) TLSO. Orthoses for similar parts of
the anatomy with much more complex control criteria have typically more complex designs as in the
WHO in (b), which provides a tenodesis action to close the fingers with wrist extension, and the
complex reciprocator, bilateral HKAFO in (d), which provides stability for the knee and ankle while
providing assistance to hip flexion.
fatigue resistance. In other instances, the loading conditions are slight, but the application is long term;
thus, the primary requirement is good compatibility
with the skin. Applications for very short-term use
under either heavy or light loading conditions are much
82
REHABILITATION, ORTHOTICS IN
Figure 3. Many material options can accomplish the same performance criteria for a particular
orthotic prescription. In this example, a tibial fracture orthosis (AFO) is constructed by three
different techniques to accomplish the same end result. Plaster can be molded directly to the
patients limb and attached to a prefabricated ankle joint (a), an isoprene thermoplastic material can
be molded directly to the patients limb attached to a metal ankle joint incorporated into a stirrup
permanently attached to the shoe (b), or prefabricated components can be applied with hand
trimming and assembly (c). Reprinted with permission from Maramed Orthopaedic Systems.
REHABILITATION, ORTHOTICS IN
83
84
REHABILITATION, ORTHOTICS IN
Materials
The choice of material varies according to durability,
strength, stiffness, skin compatibility, and fabrication
requirements. For short-term applications, prefabricated
devices that can be produced by sophisticated manufacturing techniques are often used. Thus, most any
commonly available material may be used for short-term
custom applications; materials that can be applied
directly to the patient will often be used (Figs. 3 and
911). Four basic forms of such material exist: plaster,
fabric reinforced, fiberglass reinforced, and solid sheets.
Some are thermosetting materials activated by promotors or moisture; some are thermoplastics. Devices for
long-term use tend to be custom fabricated from materials that are formed to measurements or molds of the
patient. The materials are typically thermoplastic, laminated thermosetting materials with carbon fiber, fiberglass or fabric reinforcement, leather, fabric, aluminum,
stainless steel, steel, and foam plastics and elastomers
(Figs. 113).
Figure 6. Many types of devices use components that are similar to classic orthoses, but at this
time are considered by the authors not to be classic orthoses because they are not fabricated or
applied by orthotists. An example is this acutely applied air splint for first aid or emergency,
designed to control edema and limit motion at the ankle joint for short-term use (a). Orthotic-like
devices are used to supplement various therapeutic regimens in the rehabilitation of patients
post-injury and post-surgery. This example provides continuous passive motion to the joints
through powered systems attached to orthotic-like components (b, reprinted with permission
from Orthomed Medizintechnik, GmbH), and the other one provides a corrective force to
gradually regain motion in joints with contractures, (c, reprinted with permission from Joint
Active Systems, Inc.).
REHABILITATION, ORTHOTICS IN
85
applications not in common use. The description of typical design types and materials also reflects the opinion of
the authors on the systems commonly used in orthotics
today. Many sophisticated designs and materials are
being used in research and may be commonly applied
in the future.
Some conventional devices do not strictly meet the
nomenclature system because they do not cross a joint or
control a joint. They simply are a sleeve that compresses
soft tissue to stabilize a fracture or protect a limb with
soft-tissue injuries. These devices are only for short-time
use until in injury can heal. Examples are shown in
Fig. 14.
FUNCTIONAL EVALUATION
Evaluation of musculoskeletal function is the key to adequate prescription criteria or performance criteria, for
conventional orthoses. Communication of this evaluation
by the orthopedic surgeon to the orthotist is an important
step in obtaining agreement on, and optimum use of,
orthoses in the rehabilitation of the patient. To this end,
the Committee on Prosthetics and Orthotics of the American Academy of Orthopedic Surgeons has devised
the technical analysis form that is used for recording the
functional evaluation of the patient, documenting the
abilities and disabilities of the patient, and forming a
86
REHABILITATION, ORTHOTICS IN
Figure 8. HKAFOs are generally used for the control of deformities. Axial rotation alignment of the
lower limbs can be controlled with an HKAFO commonly called a twister brace (a), which uses a
flexible cable to provide free motion at the knee and ankle in all degrees of freedom while applying a
constant axial torque for rotation correction. An HKAFO for control of valgus at the knee provides
three-point support through the soft-tissue interfacing sleeves with as little restriction to ankle and
hip flexion and extension as possible (b). An HO is often used after total hip replacement to provide
an abduction resistance to the hip during flexion to help prevent hip dislocation until the soft-tissue
healing is completed (c, reprinted with permission from Sky Medical, Inc.).
REHABILITATION, ORTHOTICS IN
87
Figure 11. EOs typically are of the custom-fabricated type with prefabricated components for the
control of elbow flexion and extension during rehabilitation post-injury (a) or elbow reconstruction, but
many are totally prefabricated designs (b, reprinted with permission from Aircast, Inc.).
88
REHABILITATION, ORTHOTICS IN
Passive
Active
Soft-tissue
interface
Alignment to
structural members
and joints
Alignment to joints and
soft tissue interfaces,
extension blocks
Feedback
load/position
Structural
members
Hip joint
Knee joint
Ankle joint
Foot
Alignment
FES
Electrode placement
orstimulation
Wraparound or
interlocking shells;
adjustable pads and straps
Feedback
Modular uprights; reinforced
load/position
shell; extension of joints and
bands; single axis; I or
2 DOF, cam or drop lock
Manual-activated
Single axis; 1 or 2 DOF;
lock
cam or drop lock
Feedback position,
Single- or multiaxis;
load-, manual-, or
1 DOF; variable stop; cam,
EMG-activated
link, or drop lock; friction
lock or resistance
resistance; elastic assistance;
single lateral or posterior
upright; medial-lateral upright
Feedback position,
Single- or multiaxis; 1 DOF
load-, manual-, or
variable stop; cam; friction
EMG-activated
resistance; elastic assistance;
lock or resistance
single lateral or posterior
upright; medial-lateral upright
Shoe insert: caliper or stirrup
attached to shoe with shank
Microprocessor, load- Implantable: electrodes,
or EMG-activated
self-contained power and
stimulus
control module, stimulator
module RF to external power
External: electrodes,
stimulator, and controls
For examples, see Figs. 15, 7, and 8. DOF, degree(s) of freedom; FES, functional electrical stimulation.
Typical Materials
Fabric, leather, hand laminates,
thermoplastics, foam or
elastomer polymers
Metals, hand laminates,
prepregs, thermoplastics
Metals, reinforced
polymers, thermoplastics
Metals, reinforced polymers,
thermoplastics
REHABILITATION, ORTHOTICS IN
89
Passive
Active
Typical Materials
Soft-tissue
interface
Alignment to joints
and structural
members
Alignment to soft
tissue interfaces
and joints,
extension blocks
Lock, stop, free,
assistive, motions
F feedback
load/position
Wraparound or interlocking
shells; adjustable padding
and straps
Modular reinforced shells;
extension of joints
and bands
Structuralmembers
Shoulder joint
F feedback
load/position
Manual-or
EMG-activated
lock or assistance
Elbow joint
Manual-or
EMG-activated
lock or assistance
Wrist joint
Manual-or
EMG-activated
lock or assistance
Hand
Lock, stop,
free, assistive,
motions
Manual-or
EMG-activated
lock or assistance
FES
orstimulation
Electrode
placement
Microprocessor-,
load- or EMGactivated stimulus
Silicone-coated
silver-braided steel,
silver-impregnated
silicone, SS electrodes,
epoxy- or
silicone-encapsulated
electronic components
Passive
Active
Typical materials
Soft-tissue
interface
Alignment to
structural members
F feedback load
Wraparound or interlocking
shells; adjustable pads and straps
Structural
members
Alignment to soft
tissue interfaces
F feedback load
Electrical
stimulation
Electrode placement
Microprocessoractivated
stimulus
90
REHABILITATION, ORTHOTICS IN
Figure 14. Fracture orthoses that do not span a joint are used for selected humeral fractures (a)
and selected isolated ulnar fractures and some soft-tissue injuries (b, reprinted with permission
from Sky Medical, Inc.).
controls one joint and does not include all joints distal to it.
For example, an orthosis that encompasses and controls
only the knee joint is termed a KO. A similar nomenclature system is shown for the upper limb and for the spine in
Figs. 18 and 19, which show the orthotic recommendation
REHABILITATION, ORTHOTICS IN
91
Figure 17. The orthotic recommendation portion of the lower limb technical analysis form provides for
description of the treatment objective
as well as a prescription recommendation for control of musculoskeletal
system by the orthosis. Reproduced
by permission from the American
Academy of Orthopaedic Surgeons,
Atlas of Orthotics, 2nd ed., St. Louis,
C. V. Mosby, 1985.
92
REHABILITATION, ORTHOTICS IN
OUTCOME
FUTURE
DEFINITIONS
1. Ortho. From the Greed orthos, meaning straight or
to correct.
2. Orthosis. Orthopedic appliance used to straighten,
correct, protect, support, or prevent musculoskeletal
deformities.
3. Orthotics (orthetics). Field of knowledge relating to
the use of orthoses to protect, restore, or improve
musculoskeletal function. (Note: This field overlaps
the field of mobility devices, including wheelchairs,
crutches, and special vehicles, for transportation of
persons with musculoskeletal disabilities. Mobility
aids will not be discussed in this article.)
4. Orthotist (Orthetist). A person practicing or applying orthotics to individual patients.
RESIN-BASED COMPOSITES
5. Custom versus prefabricated orthoses. Custom-fabricated orthoses are devices that have components
that are molded specifically to the contours of the
musculoskeletal structures of a patient. This fabrication can be accomplished by making molds, tracings,
or careful measurements of the patients anatomy for
custom shaping in the fabrication of the device. Prefabricated orthoses are made completely from prefabricated components that are fit to the patient in
standard sizes. Some systems are preassembled, and
some are not. Prefabricated components may be used
in custom-fabricated devices along with custom-fabricated components to provide a custom orthosis.
6. Modular component. A component that can be assembled from prefabricated parts and can be disassembled
and reassembled in different combinations.
7. Nomenclature. A standard set of abbreviations for
an orthosis related to the anatomic parts that are to
be controlled by the orthosis (see Figs. 1418); for
example, AFO is ankle-foot orthosis.
8. Free motion. No alteration or obstruction to normal
range of motion of an anatomic joint.
9. Assistance. Application of an external force for the
purpose of increasing the range, velocity, or force of
motion of an anatomic joint.
10. Resistance. Application of an external force for the
purpose of decreasing the velocity or force of motion
of an anatomic joint.
11. Stop. Inclusion of a static unit to deter an undesired
motion in a particular degree of freedom of an anatomic joint. Variable control parameter that can have
multiple adjustments without making a structural
change.
12. Hold. Elimination of all motion in a prescribed
degree of freedom of an anatomic joint or anatomic
structure.
13. Lock. A device that has an optional mode of holding
a particular anatomic joint from motion and that can
be released to allow motion when desired.
93
RESIN-BASED COMPOSITES
MARK CANNON
Northwestern University
Chicago, Illinois
INTRODUCTION
Composite dental restorative filling materials are synthetic resins that have had a revolutionary impact on
dental practice. No other dental materials have stimulated
such rapid change in an inarguably short period of time.
The advent of resin-based composite occurred during the
Golden Age of Dentistry and mirrored the overall effect
that high technology had on society. Virtually everyone has
been made aware of bonding or cosmetic dentistry by
the mass media. The success of bonding or cosmetic
dentistry depended on the development of esthetic dental
restorative (filling) materials such as resin-based
composites and to the advent of dental adhesives, which
allowed for the successful placement of the new esthetic
materials.
Composite resins have replaced the previous dental
restorative materials for anterior teeth, silicate cements,
and unfilled acrylic resins, because of superior physical
properties. The overall improvement in physical properties
has encouraged a great increase in the clinical use of
composite resins. Composite resins are now used in virtually all aspects of dentistry. Their application was first
limited to simple cavities in anterior teeth (incisors) or the
repair of a broken tooth. However, composite resins are
now used to cement orthodontic brackets onto teeth, seal
pits and fissures in molars and premolars, splint periodontally or traumatically loosened teeth together for stability, repair not just broken teeth, but also porcelain
restorations, revitalize and enhance the esthetic quality
of discolored or misshapen teeth. Certainly, no other dental
material systems offers such a broad range of applications
or greater opportunities for the improvement of dental
care. Researchers are working diligently to develop newer
resins that possess all the necessary qualities required of an
ideal dental restorative material, esthetic by nature
and resistant to all the deleterious effects of the oral
environment.
FABRICATION
94
RESIN-BASED COMPOSITES
Acronym
Organic compounds
Bis-GMA
Bisphenol--glycidyl methacrylate
CH3
H2C
Figure 1. Bis-GMA.
OH
O
CH3
OH
CH3
O
CH2
CH3
CH3
O
H2C
O
TEGDMA
CH2
CH3
Triethyleneglycol dimethacrylate
Figure 2. TEGDMA.
RESIN-BASED COMPOSITES
95
96
RESIN-BASED COMPOSITES
Table 1. List of Materials and Percentage of Fillers by Weight Determined by Ashing in Aira
Material
Classificationb
Manufacturer
% Fillers by Weight
Aeliteflo
Amelogen
Arabesk
Arabesk-Flow
Arabesk-Top
Ariston-pHc
Brilliant-Dentin
Brilliant-Enamel
Charisma-F
Charisma-PPF
Clearfil Photo Post
Clearfil Photo Ant.
Colte ne-SE
Concise
Dyract-Flow
Elan
EXI-119 (Z-250)c
EXI-120 (P-60)c
F-2000
Glacier
Metafil-CX
Pertac-II
Polofil-Molar
Quadrant Anterior
Quadrant Posterior
Revolution
Silux-Plus
Solitaire
Spectrum
Surefil
Tetic-Ceram
Tetric-Flow
Wave
Z-100
039317 (A3)
2CPM (A2)
70500 (A3)
82777 (A3)
81594 (A3)
A00001 ()
GE931 (A3)
GE902 (A3)
23 (A20)
2 (A10)
0035A (UL)
0024C (A3)
FBJOl (A3)
19970303(U)
9809000103 (A2)
805872 (A3,5)
030998 (A3.5)
030998 (A3,5)
19970905 (A3)
60506 (B3)
71201 (A3,5)
00634764 (A3)
63596(U)
22C (A2)
30C (A2)
710669 (A3)
6DH (U)
26 (A30)
9608244 (A3)
980818 (A2)
900513 (A3)
901232 (A3)
80608 (A3)
19960229 (UD)
54.9
72.9
71.6
61.8
71.5
74.8
75.6
75.4
76.4
68.3
84.7
59.9
71.3
80.2
55.4
71.2
77.4
78.9
80.5
78.2
41.7
70.0
78.5
58.6
65.2
53.9
54.8
64.3
75.3
79.4
75.7
64.0
60.7
79.6
b
c
RESIN-BASED COMPOSITES
97
CLINICAL APPLICATION
Bonding is a general term that is used to describe the
joining, uniting, or attaching of adhesives to an adherend
(6). Bonding describes the attachment of two materials, but
not the mechanism by which the bonding occurred. A
bonded assembly may be attached together by mechanical
means or by physical and chemical forces. The bond that
0.040.1
13
0.40.8
0.720
0.041
3550
7077
5666
4865
4454
E
F$Cc
E
P$Gc
P
F
E
E
P$Ed
P
E
G
G
P
F$Gd
98
RESIN-BASED COMPOSITES
99
INTRODUCTION
Respiratory mechanics applies the principles of solid and
fluid mechanics to pressure, flow, and volume measurements obtained from the respiratory system. The utility of
the resulting mathematical models depends on how well
they guide clinical decisions and prove consistent with the
results of new experiments. Although very sophisticated
100
the lungs follow, filling with air. When the subject is at rest
exhalation is passive. The muscles relax, the thoracic
cavity decreases in volume, and air flows out of the lung.
In addition to the solid mechanics of these structures,
analyses of fluid flows are important. The behavior of fluids
spans many regimes: convection-dominated flows in the
large airways, gaseous diffusion at the alveolar level,
interphase diffusion through the capillary walls into the
blood, and viscous flows in the alveolar ducts, capillary
spaces, and intrapleural space.
IC
TLC
IRV
VC
VT
ERV
FRC
RV
101
1
Pm
TLC
Saline
Air
Volume
Ppl
102
a catheter tipped with a small latex balloon into the thoracic esophagus. The balloon was partially inflated, but not
stretched. The theory is that both the balloon and the
esophageal wall are flaccid structures, and so pressure
changes measured by this manometry system would reflect
changes in intrathoracic pressure (9). These measurements were undertaken in intact animals and subjects
to try to separate the mechanics of the chest wall from
the properties of the lung itself.
Exhalation
flow rate
Thoracic Cage
In a manner similar to the parenchyma, the chest wall was
conceived of as an elastic structure and the slope of the
pressurevolume curve for the relaxed chest wall was
called the chest wall compliance. The active forces exerted
by the muscles (DPm) are conceived of as a normal force
applied to change the intrapleural pressure. During inhalation, expansive chest wall forces decrease the intrapleural pressure, causing expansion of the lung. If the
subject forcefully exhaled, or used the muscles to exhale
to a volume below functional residual capacity, the intrapleural pressure would increase.
These were the simplest models for the static mechanics
of the respiratory system. Pressure differences at various
points in the system are related to volume changes, and the
tissue properties were modeled as a simple elasticity
although the compliance could be dependent on lung
volume.
DYNAMIC EVENTS IN THE RESPIRATORY SYSTEM
Respiration requires the flow of gases into and out of the
lungs. Many studies investigated the nature of the fluid
flow, but early attention focused on a very simple model:
that of a resistance to air flow. If a subject inhales to total
lung capacity and then exhales to residual volume, the
volume exhaled is the vital capacity. However, if performed
with maximal expiratory effort, this experiment is called
the forced vital capacity (FVC) maneuver (10). Mathematical analysis of the resulting data showed that the volume
exhaled was almost exponentially related to time:
V FVC1 ekt
Exhaled volume
Figure 4. Maximum expiratory flow-volume maneuver at
different degrees of effort.
103
Ppl
Patm
Ppl + V/C
EPP
104
10
11
12
13
14
15
16
17
105
giving
PAO2 PIO2 PACO2 =RQ
Carbon dioxide
or
PAO2 Patm 47 FIO2 PACO2 =RQ
18
Oxygen
Content of
gas in blood
106
19
Adding the equations above would give
aP sin vt R1 dV1 =dt R2 dV2 =dt
V1 =C1 V2 =C2
Alveolar ventilation to
normal lung only
(46)
75%
70%
(46)
100%
(35)
70% (46)
Hgb
saturations,
%
( ) partial pressures
of carbon dioxide
88%
(40)
107
MECHANICAL VENTILATION
The mechanisms by which diseases affect gas transport
can be used to understand mechanical ventilation.
Because the primary determinant of carbon dioxide tension is alveolar ventilation, adjustments in respiratory
rate and tidal volume will allow control of carbon dioxide
levels. Because oxygenation is dependent on the fraction
of inspired oxygen AND upon how ventilation and perfusion are distributed, the FIO2 is just one of the controls
affecting oxygenation. Positive end-expiratory pressure
(PEEP) can be applied to try to recruit alveoli that might
be collapsed and responsible for the shunting of blood.
That is, end-expiratory pressure at the mouth is held
above atmospheric pressure to hold alveoli open. The
price paid is that normal alveoli can become overdistended. Therefore the exact level of PEEP that should
be used is still controversial (22,23).
Although there are many types of ventilators that perform many sophisticated functions, there are two basic
ways to ventilate a human being. For adults, volume-cycled
ventilators are usually used. A tidal volume is set, and
pressures measured for safety reasons. For infants, tidal
volumes are too small to accurately measure, so that
pressure-cycled ventilators are used. In this case, a peak
inspiratory pressure and PEEP are chosen, and the volume
actually delivered depends on the mechanics of the ventilator and of the infants respiratory system (24). In this
case, tidal volume becomes a variable so that safe pressure
limits are never exceeded.
Although there is much written about barotrauma
from mechanical ventilation, that is actually a misnomer.
Experiments on cells from the lungs show that when a cell
is stretched beyond a certain point, inflammatory mediators
are generated and the cell can die (25). The correct term is
volutrauma, but because we cannot measure cell stretch
adequately, pressure limits are generally respected (26).
CONCLUSION
This article does not attempt to summarize the literature
on continuum mechanics, statistical models, or tissue
mechanics of the respiratory system. However, the simple
concepts described above are essential for understanding
pulmonary function testing, respiration, and patient support with mechanical ventilators. Once these concepts are
mastered, the complex and often conflicting literature can
be critically read and understood.
108
BIBLIOGRAPHY
1. Kollef MH, Shapiro SD, Boyd V, Silver P, Von Harz B,
Trovillion E, Prentice D. A randomized clinical trial comparing an extended-use hygroscopic condenser humidifier with
heater-water humidification in mechanically ventilated
patients. Chest 1998;113:759.
2. Huang W, Yen RT, McLaurine M, Bledsoe G. Morphometry of
the human pulmonary vasculature. J Appl Physiol 1996;81: 2123.
3. Wang NS. Anatomy and physiology of the pleural space. Clin
Chest Med 1985;6:3.
4. Lichtenstein O, Ben-Haim SA, Saidel GM, Dinnar U. Role of
the diaphragm in chest wall mechanics. J Appl Physiol
1992;72:568.
5. Scarpelli EM. Physiology of the alveolar surface network. Compar Biochem Physiol Part A, Mol Int Physiol 2003;135: 39.
6. Escolar JD, Escolar A. Lung hysteresis: A morphological
view. Histol Histopathol 2004;19:159.
7. Ainsworth SB, Milligen DWA. Surfactant therapy for respiratory distress syndrome in premature neonates: A comparative review. Am J Resp Med 2002;1:417.
8. Lai-Fook SJ. Pleural mechanics and fluid exchange. Physiol
Rev 2004;84:385.
9. Milic-Emili J, Mead J, Turner JM, Glauser EM. Improved
technique for estimating pleural pressure from esophageal
balloons. J Appl Physiol 1964;19:207.
10. Pride NB. Tests of forced expiration and inspiration. Clinics
Chest Med 2001;22:599.
11. Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am
J Respir Crit Care Med 1999;158:179.
12. Hyatt RE, Wilson TA, Bar-Yishay E. Prediction of maximal
expiratory flow in excised human lungs. J Appl Physiol
1980;48:991.
13. Elliott EA, Dawson SV. Test of wave-speed theory of flow
limitation in elastic tubes. J Appl Physiol 1977;43:516.
14. Kamm D. Airway wall mechanics. Ann Rev Biomed Eng
1999;1:47.
15. Polak AG, Lutchen KR. Computational model for forced
expiration from asymmetric normal lungs. Ann Biomed
Eng 2003;31:891.
16. Zhang Q, Suki B, Lutchen KR. Harmonic distortion from
nonlinear systems with broadband inputs: Applications to
lung mechanics. Ann Biomed Eng 1995;23:672.
17. Fung YC, Sobin SS. Theory of sheet flow in lung alveoli. J
Appl Physiol 1969;26:472.
18. Brimioulle S, Lejeune P, Naeije R. Effects of hypoxic pulmonary vasoconstriction on pulmonary gas exchange. J Appl
Physiol 1996;81:1535.
19. Otis AB, McKeerow CB, Bartlett RA, Mead J, McIlroy MB,
Silverstone NJ, Radford EP Jr. Mechanical factors in the distribution of pulmonary ventilation. J Appl Physiol 1956;8:427.
20. Oku Y, Saidel GM, Altose MD, Cherniack NS. Perceptual
contributions to optimization of breathing. Ann Biomed Eng
1993;21:509.
21. Guz A. Brain, breathing, and breathlessness. Respir Physiol
1997;109:197.
22. Schmitt J-M, Vieillard-Baron A, Augarde R, Prin S, Page B,
Jardin F. Positive end-expiratory pressure titration in acute
respiratory distress syndrome patients: Impact on right ventricular outflow impedance evaluated by pulmonary artery Doppler
flow velocity measurements. Crit Care Med 2001;29: 1154.
23. Rouby J-J, Puybasset L, Nieszkowska A, Lee Q. Acute respiratory distress syndrome: Lessons from computed tomography of
the whole lung. Crit Care Med 2003;31(Suppl): S285.
24. Ligas JR, Moslehi F, Epstein MAF. Occult positive endexpiratory pressure with different types of mechanical ventilators. J Crit Care 1990;5:95.
25. Pugin J. Molecular mechanisms of lung cell activation induced
by cyclic stretch. Crit Care Med 2003;31(Suppl): S200.
26. Acute Respiratory Distress Syndrome Network (ARDS). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute
respiratory distress syndrome. NEJM 2000;342:1301.
See also CONTINUOUS
RESPIRATORY MONITORING.
See VENTILATORY
MONITORING.
RESUSCITATION.
See
S
SAFETY PROGRAM, HOSPITAL
medical and nonmedical policies; and procedures, economics, ethics, and human performance. Inappropriate drugs,
devices, and procedures; defectively designed, manufactured, and maintained medical devices; inappropriate
staffing; inability to follow procedures, neglect of duties,
inattention, and ignorance; and deficient education and
training are among the factors that increase the risk of
injury in the hospital.
The Institute of Medicine (IOM) of the National Academy of Sciences produced a report containing estimates as
high as 98,000 deaths occurring annually in U.S. hospitals
caused by medical errors (1). About 1 million medical
injuries occur annually in the United States, with
200,000 involving some negligence (2). Such iatrogenic
injury (injury caused by the physician, now more broadly
defined as injury caused by giving care in a hospital) has
been well documented (3). Medical devices used in delivering care have a finite probability of doing harm to the
patient or to the person using the device (4) and are
included as one source of iatrogenic injury. Estimates of
the percentage of device-related incidents over all incidents
vary from 1 to 11% (2).
JOSEPH F. DYRO
Setauket, New York
INTRODUCTION
This article describes the broad scope of safety issues in the
hospital and recommends ways in which hospitals should
address these issues. Particular emphasis is placed on
medical devices and instrumentation and how they interrelate with the hospitals environment, facility, patients,
and device users and other personnel. Medical device
safety depends in large part upon a comprehensive medical
device technology management program, which includes
elements ranging from technology assessment, evaluation,
and procurement to device replacement planning and
includes such components as user training, medical device
incident investigation, and device quality assurance. The
clinical engineer by education, training, and experience is
shown to be ideally suited to implement and execute a
technology management program and to lead in the effort
to assure hospital-wide patient safety. Available resources
are described including web-based training, distance
learning, standards, publications, and professional organizations.
Innovative surgical techniques, improved invasive and
noninvasive diagnostic procedures, advanced diagnostic
and therapeutic medical devices, pharmacological progress, and an overall better understanding of disease processes continue to benefit the treatment of the sick;
however, advanced technology has been a mixed blessing
to recipients of these advances. Its positive impact on
healthcare has been countered by the creation of problems
engendered by an increasingly complex medical device and
instrumentation environment. In the use of devices and
techniques, misuse or procedural error can and does occur.
Some level of risk is associated with everything that is done
to care for the patient. Healthcare professionals must keep
abreast of the advancing technologies, be aware of their
limitations and risks, and manage them. The hospital
safety program is an integral part of the system of risk
reduction and can and should be broad in scope, not limited
by undue attention to only one or two risk categories such
as slips and falls or needle sticks. It should encompass
means to address and control the risks of injury to patient
and staff, risks that arise from all sources, not only those
specifically related to medical devices, but those related to
the performance of the individual healthcare giver.
110
111
patients if improperly utilized (13). Iatrogenic complications can be introduced by infusion pumps, widely used for
intravenous and intraarterial fluid and drug administration. Incompatibility of certain drugs with the plastics from
which infusion pump administration sets are made is a
source of risk. Nitroglycerin in solutions administered by
infusion pumps has been shown to interact with certain
formulations of poly(vinyl chloride) (PVC) tubing, ultimately decreasing the potency of the drug and making
the administration of a known amount impossible to gauge.
Other examples include allergic reactions to latex gloves,
skin preparation agents, and contrast media and adverse
reactions to implantable devices such as artificial joints
and nerve stimulators.
Sound and Electromagnetic Radiation
A neonates auditory system is particularly susceptible to
injury from high sound levels as can occur in infant incubators. Diagnostic ultrasound units must be properly
designed and maintained to ensure that output levels
remain within acceptable limits recommended in safety
standards.
The hazards of ionizing radiation became well known
not long after the development and use of the X-ray
machine. A good radiation safety program is essential to
ensure that radiographic equipment and protective measures in radiographic suites meet acceptable performance
and safety standards and that operators are appropriately
trained and follow established safety procedures.
Nonionizing radiation is a significant health hazard in
all hospitals and includes UV, microwave, and laser radiation. Ultraviolet therapy is employed in the treatment of
some skin disorders. However, UV radiation can adversely
affect the eye (keratitis) and the skin (erythema and carcinogenesis). Microwave radiation is commonly used in
physical therapy for diathermy treatment of patients.
Microwave effects are largely thermal, with the eye being
the most susceptible organ (cataractogenesis). Surgical
lasers are particularly hazardous since the beam can travel
large distances with little attenuation and can reflect off
surfaces in the room. The intensity of the beam is of
necessity sufficient to burn body tissue as is required in
surgical procedures. Momentary eye contact with the beam
can cause severe eye damage. A laser safety program is
recommended wherever lasers are used. Eye protection
and restriction of the area to trained personnel are essential steps in the program.
Alarms
The Joint Commission on Accreditation of Healthcare
Organizations identified appropriate attention to alarms
as one of six patient safety goals of 2003 (14). Alarms are
sometimes ignored, unheard, unnoticed, misinterpreted, or
disabled. A life-threatening alarm that goes unattended
can have disastrous consequences for the patient. Alarms
are rendered ineffective for a host of reasons, some of which
are listed here. Frequent false alarms cause the care givers
to relax their guard to the point of ignoring a real alarm
condition when it occurs. Doors to patient rooms, closed to
give the patient some respite from the noise in the corridor
112
provide adequate pressures and flows for the proper operation of such devices as suction machines, pneumatically
powered surgical instruments, ventilators, and anesthesia
machines.
Water
A hospital must have an adequate supply of water (20).
Because it is in direct contact (through a membrane) with a
patients blood, the water used in hemodialysis must be
monitored and its components controlled. Numerous
adverse reactions from untreated water have occurred
(21). Components that can affect the dialysis treatment
have been identified and include insoluble particles, soluble organics and inorganics, heavy metals, bacteria, and
pyrogens.
Electrical Power
The performance of sensitive electronic medical devices
can be adversely affected by irregularities in electrical
power distribution systems. Line voltage variations, line
transients, and interruption of power can all result in harm
to the patient by adversely affecting the performance of
such devices as physiological monitors, ventilators, electrosurgical units, and clinical laboratory analyzers.
113
Environment
Those elements within a hospital environment that can
influence the safe operation of a medical device include
such things as medical and nonmedical devices that are not
directly involved in a patients care, people, electromagnetic interference, cleanliness, psychological factors, biomechanics, and natural and unnatural disasters. The
environment in which medical devices are used has grown
beyond the hospital to now include emergency vehicles,
ambulatory care facilities, long-term care facilities, and the
home. The hospital, to the extent that it furnishes devices
for patient use, must assume the responsibility for ensuring that these devices are safe and effective.
DeviceDevice Interaction
The hospital has become a complex electrical environment
where incompatibility can exist between medical devices
(24). For example, electrosurgical units have obscured
electrocardiographic traces on cardiac monitors, defibrillator discharges have damaged internal pacemakers, and
electrical transients have modified patient ventilator rates.
Nonmedical Devices
People
Elevators, escalators, doors, stairwells, and staff and patient care areas affect the level of hospital safety. A patient
room that is too small results in crowding of medical
devices, personnel, and patient. Crowding restricts rapid
access to necessary devices and instruments and interferes
with access to the patient. Poorly maintained and designed
elevators delay a caregivers access to a patient. Fire doors
propped open or emergency exit doors propped shut pose
serious hazards in the event of fire. Fire is particularly
hazardous in an environment in which an individuals
ability to evacuate is compromised by illness or disability.
A closed door to a patient room may afford the patient some
quiet from the noise from the outside, but it can also
attenuate a bedside alarm to make it inaudible to the staff.
Sanitation Systems
114
Psychological Factors
Periontogenic (having its genesis in the surroundings)
illness afflicts patients and staff. Such illness has its roots
in the stresses engendered by the high technology surroundings and includes such syndromes as intensive care
unit (ICU) psychosis, the adverse psychological impact of
the ICU setting. Dehumanization of patients can lead to
such neuroses and psychoses as depression, denial, and
dependency.
Biomechanics
Facility
Operator
Device
Environment
Patient
Safety
Security
Hazardous materials and waste
Emergency
Life safety
Medical equipment
Utility systems
115
Safety Committee
The safety management plan requires a hospital to identify
processes for examining safety issues by appropriate hospital representatives, that is, the safety committee, now
often called the environment of care committee. The
JCAHO refers to the safety committee as a multidisciplinary improvement team and defines its activities and
responsibilities as follows:
Safety issues are analyzed in a timely manner.
Recommendations are developed and approved.
Safety issues are communicated to the leaders of the
hospital, individuals responsible for performanceimprovement activities, and when appropriate, to
relevant components of the hospital wide patient
safety program.
Recommendations for one or more performance
improvement activities are communicated at least
annually to the hospitals leaders.
The safety committee serves as a forum for reports from
the seven environment of care areas. For example, the
safety committee will receive reports as specified in the
hospitals medical equipment management plan, including
performance monitoring data and incident investigation
reports. Serving as a reporting forum is an essential part of
the safety committees role. However, the great value of the
safety committee is found in its ability to subject these
reports to multidisciplinary analysis. Careful analysis
from a representative range of perspectives will produce
communications, recommendations, and performance
improvement activities that enhance safety throughout
the hospital. Hospitals may assign managers to oversee
The committee is a means by which formal lines of communication can be exercised. A hospital has various committees that relate in some fashion to an overall hospital
safety committee (environment of care committee). Each
committee necessarily deals for the most part with rather
narrow issues. Those committees that have the strongest
influence on overall hospital safety are listed in Table 1. No
two hospitals are alike and the names of the committees
may vary from one institution to the next.
Participation of key individuals, representing the
entire spectrum of services provided within the hospital,
in the work of the safety committee as well as in the work of
the other committees listed is an integral component of the
hospital safety program. Formal communication channels
must be created between these committees and the
safety committee. Committee attendance is an aid to
interdepartmental communication. Transfer of information in an informal setting in a face-to-face meeting
before or after a committee meeting can often be more
effective, rapid, and accurate than written or telephone
communications.
Specialty medical
services
Emergency
resuscitation
Medical board
Infection control
Operating room
Credentials and
privileges
Utilization review
Capital equipment
116
Staff development
Environmental
health and safety
Quality assurance
Radiation safety
Infection control
Materials
management
Fire marshall
Information
services
Clinical
engineering
Departments
The departments, offices, and authorities that play important roles in the hospital safety program are shown in
Table 2.
Risk management is a key element in any hospital safety
program (31). It has become not only a moral, but a
financial necessity to provide a safe environment for the
staff and patients. It is the risk manager who must make
recommendations, in the face of cost containment efforts,
on the investment of capital in monitoring systems and
modern equipment as a means of reducing risk. Risk
management can determine a course of action aimed at
reducing risk through, for example, increased surveillance
of the patient by appropriate monitoring devices such as
electrocardiographs, capnometers, blood pressure monitors, and pulse oximeters. Should an analysis show that
the main problems lie in human error, clinical engineering
and staff development might implement an educational
program as a response. For example, human error, rather
than equipment failure, appears to be the primary factor in
most preventable anesthesia mishaps. Increased risk management initiatives can reduce these adverse incidents.
Cost-effective anesthetic practices actually require using
the most up-to-date and well-maintained equipment. The
risk management component is central to controlling the
costs of safety. Care must be taken to deploy risk management resources judiciously. A disproportionately large
amount of attention has been focused on some relatively
minor safety issues, such as electrical safety, while by
comparison few resources have been commanded to
address issues that pose greater risks to patient safety,
such as slips and falls (32).
Materials management is generally responsible for the
acquisition and distribution to patient floors of a wide variety of device accessories and disposable products. Prepurchase evaluation of these items should not be overlooked.
Clinical engineering is often in a position to lend its expertise
in device testing to the evaluation of new products proposed
for addition to the hospitals standing inventory.
Environmental health and safety is concerned with such
issues as fire safety; air quality; spillage, handling, and
storage of chemicals and unidentified substances; and
noise abatement.
Radiation safety is concerned with the protection of
patients and personnel from the effects of ionizing radiation (33). The primary aim of radiological protection is to
provide an appropriate standard of protection for humans
without unduly limiting the beneficial practices giving rise
117
issues. The clinical engineering departments responsibilities with regard to the hospital safety program should
include the implementation and execution of a medical
device technology management program.
Technology Management
Medical device technology management is the sound foundation upon which any safety program must be built.
Technology management is the management of medical
devices throughout their useful life and includes selection
and acquisition and eventual replacement (38). Elements
of technology management follow:
Strategic planning (technology assessment)
Acquisition (specification, evaluation, purchasing)
Utilization and asset management (impact analysis)
Medical device service (inspection, maintenance, repair
and modification)
Replacement planning
When a technology management program is run effectively, a hospital can be assured that the need for all
medical devices has been ascertained; that medical devices
have been properly evaluated, selected, purchased,
inspected, and calibrated for optimal performance and
safety; that all users of the devices are appropriately
trained; that the devices will be maintained on a regular
basis; that service will be provided promptly so that patient
care will not be disrupted; that a system of tracking and
identifying every medical device will be in place; that the
device is retired from service at the appropriate time; and
that device replacement planning ensures continuity of
technological support. Documentation of all elements of
the system is essential. A deficiency in any one of the above
elements can increase the exposure of a hospital patient or
employee to injury. From technology management flow all
other aspects of a safety program.
Clinical Engineering
Strategic Planning
118
Replacement Planning
All medical devices reach the point in their lives where
replacement becomes necessary because of decreased reliability, increased downtime, safety issues, compromised
care, increased operating costs, changing regulations or,
simply, obsolescence. Healthcare organizations have limited funding for capital purchases with many under strict
budgeting guidelines. Replacement based on anecdotal and
subjective statements and politics create havoc related to
finances, morale, and operations. Clinical engineering
departments are impacted if they do not have a replacement plan when major repairs occur in older equipment.
The ideal healthcare technology replacement planning
system would be facility-wide covering all clinical equipment, utilize accurate, objective data for analysis, be flexible enough to incorporate nonequipment factors, and be
futuristic by including strategic planning related to clinical
and marketplace trends and hospital strategic initiatives
related to technology. The plan should encompass many
factors related to cost benefit, safety, support, standardization, and clinical benefit (44).
Medical Device Recall System
A medical device recall system should be in place in all
hospitals to receive recall notices, hazard bulletins, and
safety alerts and to disseminate them to the appropriate
authorities (45). The system should have a means for
documenting any corrective actions required and implemented. The pharmacy typically operates a separate drug
recall system. The medical device safety officer (see below)
should manage the recall system. Close interdepartmental
communication is required. All clinical departments, ancillaries, and support or service departments within the
hospital are typically involved in medical device recall
system. Virtually all types of medical devices are subject
to recall: reusables or disposables, accessories and supplies, and capital equipment. Every medical device from
tongue depressor to computed tomography (CT) scanner
are included in the system.
Several publications contain hazard and recall notices
including FDA Enforcement Report, Biomedical Safety
Standards Newsletter, and Health Devices Alerts (see
Reading List).
IncidentAccident Investigation and Reporting
The hospital safety program should encompass the
mechanism to respond to an accident or incident in which
a patient or staff member is injured (46). Incidents and
accidents associated with medical devices and instrumentation fall within the purview of the clinical engineering
department. The Safe Medical Devices Act of 1990 requires
that the manufacturer of a medical device be notified
within 10 business days if one of its devices contributed
to death or serious injury. The manufacturer, under FDAs
Mandatory Device Reporting (MDR) regulation, is
required to report these incidents to the FDAs Center
for Devices and Radiological Health. Manufacturers are
required to report to the FDA when they receive information from any source which reasonably suggests that a
119
120
enhance patient safety through the application of engineering skills to solve problems of medical device selection,
application, utilization, and safety (56,57). The proactive
engineer will implement solutions to problems before they
occur. Root-cause-analyses and failure modes and effects
analysis (FMEA) will aid the engineer in determining what
is wrong with the system and what needs to be fixed
(58,59).
Medical Device Safety Officer
The medical device safety officer (MDSO) will one day be
commonplace in hospitals. The clinical engineer is well
suited to serve in this role and to manage the medical
device safety program.
Postmarket Surveillance
Improved postmarket surveillance of medical device performance and safety is needed to provide more device
problem feedback to the manufacturer, regulatory authorities, and to the hospital itself (60). Such feedback enables
enhanced device design, revisions in standards, and
improvements in educational programs with the ultimate
goal of reduction in hazards. Improved methods are
required to determine the prevalence, nature, and causes
of medical device-related errors.
BIBLIOGRAPHY
1. Kohn LT, Corrigan JM, Donaldson MS, editors. To Err is
Human: Building a Safer Health System. Washington, DC:
National Academy Press; 2000.
2. Trandel-Korenchuk DM, Trandel-Korenchuk KM. Legal
forum, malpractice and preventive risk management. Nurs
Admin Q 1983;7:7580.
3. Steel K, Gertman PM, Crescenzi C, Anderson J. Iatrogenic
illness on a general medical service at a university hospital. N
Engl J Med 1981;304:638641.
4. Abramson N. et al., Adverse occurrences in intensive care
units. JAMA, J Am Med Assoc 1980;244:15821584.
5. Enhancing Patient Safety: The Role of Clinical Engineering.
Plymouth Meeting, PA: American College of Clinical Engineering; 2001.
6. JCAHO. 2001. Revisions to Joint Commission standards in
support of patient safety and medical/health care error reduction. Joint Commission on Accreditation of Healthcare Organizations. Oakbrook Terrace, IL.
7. Shojania KG, Duncan BW, McDonald KM, Wachter RM,
editors. Making Health Care Safer: A Critical Analysis of
Patient Safety Practice. Evidence Report/Technology Assessment No. 43 (Prepared by the University of California at San
FranciscoStanford Evidence-Based Practice Center under
Contract No. 290-97-0013), AHRQ Publication No. 01-E058,
Rockville, MD. Agency for Healthcare Research and Quality;
2001. p 668.
8. Institute of Medicine. Crossing the Quality Chasm: A New
Health System for the 21st Century. Washington, DC:
National Academy Press; 2001.
9. Bogner MS, editor. Human Error in Medicine. Hillsdale, NJ:
Lawrence Erlbaum Associates; 1994.
10. Shepherd M. Systems approach to medical device safety.
In: Dyro JF, editor. The Clinical Engineering Handbook.
Burlington, MA: Elsevier; 2004.
121
Further Reading
Wildavsky A. Searching for Safety. New Brunswick, NJ: Transaction Publishers; 1989.
ACCE News. Plymouth Meeting, PA: American College of Clinical
Engineering (bimonthly).
Accreditation Manual for Hospitals. Chicago: Joint Commission on
Accreditation of Healthcare Organizations (annual).
Biomedical Instrumentation & Technology. Arlington, VA: Association for the Advancement of Medical Technology (bimonthly).
Biomedical Safety & Standards. Hagerstown, MD: Lippincott
Williams & Wilkins (semimonthly).
Gendron FG. Unexplained Patient Burns: Investigating Iatrogenic
Injuries. Brea, CA: Quest Publishing Co.; 1988.
FDA Enforcement Report. Rockville, MD: U.S. Food and Drug
Administration (weekly).
Health Devices Alerts. Plymouth Meeting, PA: ECRI
(semimonthly).
Health Facilities Management. Chicago: Health Forum, Inc.
Bronzino JD. Management of Medical Technology. Boston: Butterworth-Heinemann; 1992.
Kolka JW, Link DM, Scott GG. European Community Medical
Device Directives:Certification, Quality Assurance and
Liability. Fairfax, VA: CEEM Information Services; 1992.
Joint Commission Perspectives on Patient Safety, Oakbrook
Terrace, IL: Joint Commission Resources (monthly).
Journal of Clinical Engineering. Lippincott Williams & Wilkins,
Hagerstown, MA (quarterly).
Shojania KG, Duncan BW, McDonald KM, Wachter RM. editors,
Making Health Care Safer: A Critical Analysis of Patient
Safety Practice. Evidence Report/Technology Assessment No.
43, AHRQ Publication No. 01-E058, Rockville, MD: Agency for
Healthcare Research and Quality, 2001.
Geddes LA. Medical Device Accidents and Illustrative Cases.
2nd ed. Tucson: Lawyers & Judges Publishing Company; 2002.
MD&DI/Medical Device & Diagnostic Industry, Los Angeles, CA:
Canon Communications (monthly).
Medical device user facility and manufacturer reporting,
certification and registration. 21 CFR Part 803, July 31,
1996.
NCPS Triage Cards for Root Cause Analysis. National Center for
Patient Safety, Department of Veterans Affairs, 2001.
National Electrical Code: NFPA 70. Quincy, MA: National Fire
Protection Association, 2002.
Fish RM, Geddes L. Medical and Bioengineering Aspects of
Electrical Injuries. Tucson: Lawyers & Judges Publishing
Company; 2003.
122
SCOLIOSIS, BIOMECHANICS OF
TENANCE, BIOMEDICAL; GAS AND VACUUM SYSTEMS, CENTRALLY PIPED MEDICAL; IONIZING RADIATION, BIOLOGICAL EFFECTS OF; RADIATION PROTECTION
INSTRUMENTATION; X-RAY QUALITY CONTROL PROGRAM.
SCAFFOLDS.
ELECTRON.
SCANNING FORCE.
SCANNING TUNNELING.
SCOLIOSIS, BIOMECHANICS OF
I.A.F. STOKES
C.E. AUBIN
Polytechnique Montreal
Montreal, Quebec, Canada
INTRODUCTION
Scoliosis deformity occurs in the spine quite frequently,
especially in growing children. In spite of the attention
given to this deformity over the past century, still very little
is known about its etiology or progression mechanisms.
There are a number of health related consequences of a
progressive scoliosis. In large scoliosis deformities there is
impairment of respiratory and cardiovascular function. If
progressive, the deformity produces thoracic compromise,
pain, and degenerative changes in the spine. In large curves
that have been surgically fused, there may be iatrogenic
problems secondary to multisegmental arthrodesis. Although
scoliosis is often perceived as having a minimal cosmetic
impact, it has psychosocial consequences (13).
SCOLIOSIS, BIOMECHANICS OF
Transverse Plane. Axial rotation of vertebras accompanies the lateral deviation. The vertebral rotation can be
measured from a frontal plane radiograph by grading the
positions of the vertebral pedicles relative to the center of
the vertebral body. Also, templates and formulas have been
developed to convert these pedicle offsets into estimates of
the rotation in degrees. The rotation can be measured more
directly from transverse plane images obtained by computed tomography (CT) scanning or magnetic resonance
imaging (MRI). The usual rotation of the vertebral bodies is
to the convex side (5). Asymmetries of the vertebras also
develop, probably as a result of altered stress on these
bones (6). The back surface rotates in the same sense,
producing a rib hump (gibbosity). Back surface rotation
correlates weakly with the scoliosis magnitude as measured by the Cobb angle (7), leading to the idea that curve
magnitude could be measured topographically, without
X rays. However, the back surface rotation is of lesser
magnitude than the vertebral rotation (8), which in turn
is of lesser magnitude than the Cobb angle, so this attenuation of the asymmetry as seen at the surface produces
technical measurement difficulties.
Stereoradiography and stereophotogrammetry have
been used to document the transverse plane deformity in
patients with idiopathic scoliosis with simultaneous radiography to record the skeletal shape (9). The back surface
rotation was reported to be greatest at the level of the apex
of a lumbar scoliotic curve, but located as much as four
vertebras lower than the apex in thoracic and thoracolumbar curves (9). Thus the surface deformity is apparently
augmented by the effects of the rib cage where the ribs
point downward. In thoracic curves the radiographic rotation of vertebras is reported to be greatest on average at the
apex (defined as the most laterally deviated vertebra), but
with a range of three vertebras above to three below (9,10).
In most of the lumbar curves the greatest surface rotation,
the maximal vertebral rotation, and the apex coincides.
The axial rotation of the surface had a variable relationship
with the Cobb angle and in all cases was less than the Cobb
angle (11). The amount of back surface rotation is less than
the amount of axial rotation of the underlying vertebras
(9).
Coupling of Rotations. Coupling is the term used to
describe the tendency of the spine while moving intentionally in one plane to produce secondary or coupled motion in
another plane. Two kinds of coupling can be defined,
orientation and kinematic. Orientation coupling describes
the relationships between the linear or angular displacements of a single vertebra from its reference or nonscoliotic
position. Kinematic coupling is defined as the association of
two variables describing the relative motion of two vertebras without regard to forces. Kinematic coupling has
described from in vivo measurements of normally curved
spines (1214). The relationship may be altered by adaptation of bone and soft tissue resulting from the scoliosis
deformity.
Lateral bending of the healthy lumbar spine is accompanied by a rotation in the same direction as that seen in
scoliosis (15); however, the coupling of axial rotation with
lateral bending is in the opposite sense in the thoracic spine
123
Paravertebral
height difference
Angle of trunk
inclination
124
SCOLIOSIS, BIOMECHANICS OF
ZG
XG
ZV
ZS
XR
YG
XV
XS
yV
(a)
Local
(vertebra)
yS
(b)
Regional
(curve)
(c)
Spinal
(spine)
(d)
Global
(body)
Figure 3. The hierarchy of four coordinate systems defining spinal geometry: (a) Local coordinates based on a vertebra. (b) Regional, curve-based coordinates defined by the end vertebras of a
curve or other spinal region. (c) Spinal coordinates, defined by the
Z axis passing through the centers of the most caudal and cephalad
vertebrae of the entire spine. (d) Global, whole-body-based coordinate system, with its origin at the base of the spine (S1), and the
Z axis vertical (gravity line).
SCOLIOSIS, BIOMECHANICS OF
125
FUNCTIONAL ANATOMY
Spine: Vertebras, Disks, Facet Joints
The structure and function of the spinal column depends on
a complex interaction between the vertebral bodies, the
articulations between their posterior elements (facet, or
zygoapophyseal joints), interconnecting ligaments and
intervertebral disks, the rib cage and the trunk musculature. In a scoliosis the vertebras become wedged and
twisted, the intervertebral disks become wedged, and there
is a variable degree of adaptive changes in the soft tissues
(ligaments, muscles, etc.) that probably increase with age.
The ribs are more sharply angled on the convex side, and
this asymmetry, together with the axial rotation component of the deformity produces the rib hump or gibbosity
that is the most evident outward indication of the deformity. Surgical treatment of adult scoliosis is more difficult
in part because of the adaptive changes and the typically
greater curve magnitude and cardiothoracic compromise.
The Spinal Motion Segment
The spinal motion segment is a structural unit of the spine
consisting of two vertebras and the intervening soft tissues.
It is a valuable tool in spinal biomechanics because it is the
basic element of the spinal column. Once motion segment
behavior is defined, the behavior of the whole spine can be
represented by a series of fundamentally similar components. In the absence of scoliosis, the motion segment can
be considered as being symmetrical about the sagittal
plane, thus right and left lateral bends, axial rotation
and shear are theoretically symmetrical. The presence of
the posterior elements (zygoapophyseal or facet joints and
the ligaments) introduces differences between the flexion
and extension behaviors. The presence of these posterior
structures also produces a posterior displacement (relative
to the disk center) of the effective structural axis of the
motion segment. The stiffness of the lumbar motion segments has been described by a stiffness matrix, and by an
equivalent beam structure (31).
Ribcage and Costovertebral Articulations
126
SCOLIOSIS, BIOMECHANICS OF
X-ray
tube
Film
SCOLIOSIS, BIOMECHANICS OF
S1
I2
I2
S1
S2
I1
O
I1
S2
(a) STEREO
127
(b) BIPLANAR
Figure 6. Principles of stereo and biplanar radiogaphy. Stereophotogrammetry principles are used to identify the 3-D positions of
object points. The location of the object points can be visualized as
the intersections of lines joining the X-ray sources to the corresponding image points.
Tomography
Computerized tomography provides several measures of
vertebral and thoracic rotation in the transverse plane
(53). However, this method has technical difficulties
because of the need to select the orientation of the image
plane correctly: usually a global transverse plane is used
that is not coincident with the local or regional planes in
the deformed spine. While this technique can obtain rotation both at the vertebral level and in the trunk cross-
128
SCOLIOSIS, BIOMECHANICS OF
Figure 8. Example of raster stereophotograph of the back surface of a person with scoliosis. The back surface is illuminated by a
square grating pattern of lines. These lines appear curved when
viewed from a different angle. This system can be calibrated (by a
priori knowledge of the geometry, or empirically by measuring the
distortion of the grid when projected on to a surface of known
shape. This measurement technique is suitable for automatic
measurement, for example, by computer analysis of a digital
image.
SCOLIOSIS, BIOMECHANICS OF
129
Figure 9. Range sensing topographic scanner (two of the six cameras that surrounds the subject are shown on left panel) and biplanar X-ray
system (middle panel) for concurrent surface and spine imaging, showing typical superimposed 3D torso spine model (right panel).
of systemic growth factors (70), abnormal collagen synthesis (71), and abnormalities of muscles and neuromuscular
control (72). Recently, Moreau et al. (73) reported that
bone cells of patients having surgery for idiopathic scoliosis had an abnormal response to melatonin, implicating
a dysfunction melatonin signaling in these patients.
However, all these empirical findings have not yet been
incorporated into a coordinated theory of the cause of
idiopathic scoliosis.
BIOMECHANICS OF SCOLIOSIS PROGRESSION DURING
GROWTH
Scoliosis progression is associated with the rate of skeletal
growth (74,75). In the progression of a small deformity to a
large one, it has been proposed that a small lateral curvature of the spine would load the vertebras asymmetrically
(76), leading to asymmetrical growth in the vertebral
growth plates. This acceleration of the deformity associated with mechanically modulated growth has been
termed a vicious cycle (77) starting after a certain threshold of spinal deformity has been reached. This theory of
spinal growth sensitivity to loading asymmetry must, however, explain why the normal spinal curvatures (kyphosis
and lordosis) in the sagittal plane do not progress into
hyperkyphosis and hyperlordosis by the same mechanism,
although progressive deformity in Scheuermanns kyphosis has been attributed to a similar mechanism (78). This
concept of a biomechanical mechanism of progression of
deformity is attractive intuitively, and has been incorporated into the rationale for brace and surgical treatments
(79). However, it cannot be quantified without better
knowledge of the normal spinal loading and the alteration
of loading in scoliosis, and better understanding of the
sensitivity of growth to the time course of mechanical load
130
SCOLIOSIS, BIOMECHANICS OF
(e)
(d)
(a)
(a)
(b)
(c)
(a)
(c)
(b)
(d)
(c)
(f)
(e)
Figure 10. Possible correction force components applied by surgical instrumentation to the spine. Lateral force (a); coronal moment (b); sagittal force (c); sagittal moment (d); distraction force
(e); axial moment (f).
SCOLIOSIS, BIOMECHANICS OF
131
132
SCOLIOSIS, BIOMECHANICS OF
Figure 13. Stapling of intervertebral disk interspace. (Reproduced from Ref. 109, with permission.)
introduced by Dwyer and Schafer (107) and was popularized with the Zielke instrumentation in the 1981s (108).
Anterior fusion is considered controversial (e.g., because of
risks to anterior structures including nerves and major
blood vessels), so posterior instrumentation with fusion is
still considered the gold standard.
Staples applied between adjacent vertebras are a promising minimal invasive technology to correct spinal deformities (109) (Fig. 13). Compression staples are used on the
convex side of a spine curve to reduce growth while distraction staples are placed on the concave side to accelerate
growth.
Testing of Spinal Instrumentation (Construct Design)
Much of the understanding about results of spinal instrumentation and fusion is empirical, based on follow-up
studies. Biomechanical principles should be able to provide
additional information. The use of surgical instrumentation has a direct mechanical effect on the fused part of the
spine, and an indirect effect on the unfused region. It
remains as a challenge to biomechanics to further our
understanding of the interactions between the spine, the
instrumentation, and the muscular and other forces. The
muscles, and their control presents the greatest difficulties, since CNS (central nervous system) control of trunk
balance is so poorly understood.
There are three basic types of spinal implant construct
testing: tests of individual implant components (hooks,
screws, rods etc.), tests of the connections between an
implant, and the spine and tests of complete instrumentation assemblies. All can be tested in simulations of in vivo
conditions to evaluate their performance. Laboratory testing of a spinal construct (consisting of a test instrumentation applied to a standardized spinal specimen) can provide
information about its flexibility, strength, and fatigue life.
Components, such as pedicle screws, may be tested in pullout (110) or bending. The challenge in all these tests is to
establish conditions that are representative of the in vivo
situation. Both strength and stiffness are desirable properties of instrumentation, and fatigue testing is important to
establish whether instrumentation will mechanically fail
SCOLIOSIS, BIOMECHANICS OF
P
(a)
(b)
133
134
SCOLIOSIS, BIOMECHANICS OF
Figure 16. Virtual reality spine surgery simulator. The left panel
shows one part of the virtual surgery room with the operating
table, the patient and the exposed spine, as well as the radiographs
and a magnification of the selected vertebra. The right panel shows
an operator that is performing a virtual reality surgery (using
stereo stereoscopic glasses and a 3D mouse).
CONCLUSION
Scoliosis is a costly problem in terms of both healthcare
resources and human suffering. Many cases have unknown
etiology, and there may be a genetic component in their
causation that is modified by environmental factors.
Mechanical analyses of scoliosis as a buckling phenomenon have not been very illuminating, possibly because
they are single plane models and do not incorporate rotation or other coupling. The interactions between biomechanical factors and spinal stability during growth are
probably important in most scoliosis deformities, irrespective of their initial cause. Biomechanical factors including
motion segment coupling, spinal length and slenderness,
muscle asymmetry, and postural sway, are apparently
relevant in the development and progression of these
deformities.
Geometrical aspects of scoliosis can be better documented and understood with 3D measurement including low
dose 3D X-ray techniques. These provide a more complete
picture of the deformity than the relatively inaccurate
single plane Cobb angle measurement. Noninvasive surface measurement techniques show promise, but there is
still a need to establish their relationship to radiographic
measurements, especially during progression of a curve.
Although many experimental and biomechanical models of scoliosis have been developed, the mechanisms
behind the spinal deformity process and its treatment
SCOLIOSIS, BIOMECHANICS OF
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SCREEN-FILM SYSTEMS
SCREEN-FILM SYSTEMS
X-ray photons
X-ray photons
ZHENG FENG LU
Columbia University
New York, New York
Light photons
Light photons
INTRODUCTION
Projection radiography generates the majority of the imaging volume in a typical hospital-based radiology department. Figure 1 illustrates the basic geometry for projection
radiography. As shown, an X-ray beam incidents upon and
transmits through the patient. Differential attenuation
occurs as X-ray photons interact with tissues in the patient.
Consequently, an altered X-ray distribution pattern is
generated behind the patient. This altered X-ray pattern
can be recorded by an image receptor placed underneath
the patient.
Film has been utilized as an image receptor since the
very beginning of radiographic imaging. The first radiograph of a living hand was exposed by Roentgen in 1895
using a photographic plate (1). Film is sensitive to both
X rays and light photons. However, the sensitivity of film to
direct X-ray exposure is low. In order to overcome this
problem, the fluorescent screen was developed shortly after
the discovery of X rays to be combined with the film as an
image receptor. Fluorescence, as used in radiography,
refers to the phenomenon that the absorption of X rays
by crystals of certain inorganic salts (called phosphor) is
followed by the emission of light photons (2). The emitted
light photons are then utilized more efficiently to expose
the film that is sandwiched between the screens (see
Fig. 2). These fluorescent screens are also called intensifying screens. Initially, calcium tungstate was the phosphor
of choice for screens in radiography (3). Over the years,
especially since early 1970s, more efficient phosphor materials have been developed, such as rare earth phosphors
(2,57). The rare earth elements are found in a row of the
periodic table of the elements with the atomic numbers
5771. The most common rare earth phosphor currently
available is godalinium oxysulfide (4). Phosphors, other
than rare earth types, are used as well, such as yttrium
tantalate (57).
X-ray tube
Double-screen/double-emulsion
Single-screen/single-emulsion
Patient
Grid
Image receptor
Figure 1. Illustration of the basic geometry for projection radiography.
INTENSIFYING SCREEN
Since only a small percentage (26%) of the X rays can be
absorbed by the emulsion of the film, the sensitivity of the
film alone is very low (2). With the screenfilm combination,
SCREEN-FILM SYSTEMS
139
140
SCREEN-FILM SYSTEMS
Atomic Number of
Heaviest Element
74
56
56
64
57
57
39
K-Edge, keV
Conversion Efficiency, %
69.5
37.4
37.4
50.2
38.9
38.9
17.0
3.5
6
13
15
13
12
18
Light Emission
Spectrum
Blue
Blue
Blue
Green
Blue
Green
Blue
(340540
(330430
(350450
(400650
(360620
(480650
(370630
nm)
nm)
nm)
nm)
nm)
nm)
nm)
Supercoat
Emulsion ~ 10 m
Base ~ 0.2 mm
SCREEN-FILM SYSTEMS
141
Figure 5. Photomicrographs of flat, tabular-shaped grains with the crystals orientated with the flat
side parallel to the film base (a) and three-dimensional (3D) silver halide grains (b). (Courtesy of
Dr. R. Dickerson of Eastman Kodak Company.)
The bromide atom, Br, then migrates out of the crystal into
the gelatin while the free electron becomes subsequently
trapped at a sensitivity speck. The trapped electron (negatively charged) at the sensitivity speck attracts a mobile
silver ion, Ag, (positively charged), and the two combine to
form a silver atom, Ag, at the sensitivity speck:
Ag electron ! Ag
142
SCREEN-FILM SYSTEMS
Comments
0.0
0.150.20
0.452.20
3.0
> 3.5
Developed film
Usually, the film is developed immediately after the Xray exposure is made. If the film is delayed in developing,
the film speed and contrast will be reduced. This phenomenon is called latent image fading that can also be
explained by the mechanism mentioned above.
Optical Density
In photographic print film, the more exposure the film
receives, the brighter the print film will be. In screen-film
radiography, it is the opposite because X-ray film is a
negative recorder. An increased X-ray exposure produces
darker film. The degree of darkness of the developed film is
defined by a term called optical density or, simply, density
(4). Shown in Fig. 6, if the incident light intensity from a
viewbox, where the film is read, is given by I0, and the
transmitted light intensity through the film for one particular spot is given by It, then the optical density (O. D.) at
that location is given as the 10 based logarithm of the ratio
of the incident light intensity versus the transmitted light
intensity:
I
4
O:D: log10 0
It
For example, if the transmittance at one film location is
10%, then the optical density of that location is 1.0. Notice
the relationship of the transmittance and the optical
density is logarithmically compressed. Hence, if the
optical density is 3.0, then the transmittance is only
0.1%. The optical density is often measured by a device
called a densitometer. A densitometer has a small
sensitive area (aperture), where the light intensity without film in the light beamI0 is measured; then with the
film inserted and the region of interest covering the
aperture, the densitometer, measures the light transmitted through the filmIt. The optical density is read
accordingly when the read-out button is pressed on the
densitometer.
Table 2 lists a range of optical densities. Optical density
0.0 is reached only when the light transmission through
the film is 100%, which is not practically possible. Even
when a fresh unexposed film is processed, it will still have a
low film density of 0.15 O.D., which is known as the film
base plus fog. The base density is caused by the absorption
of light through the film base material. The current polyester film base is usually slightly blue-tinted in order to ease
3
2.5
2
1.5
1
0.5
0
0.00
0.30
0.60
0.90
1.20
1.50
1.80
2.10
2.40
2.70
3.00
SCREEN-FILM SYSTEMS
143
4.00
4.00
3.50
3.50
3.00
3.00
2.50
2.50
2.00
2.00
1.50
1.50
1.00
1.00
0.50
0.50
0.00
0.00
0.30
0.60
0.90
1.20
1.50
1.80
2.10
2.40
2.70
3.00
Film contrast
0.00
3.30
Film B
Contrast of film A
Contrast of film B
DS DB
1:75
6
log ES log EB log ES log EB
where DS is 2.0 O.D. above the base plus fog and DB is 0.25
O.D. above the base plus fog. The parameters ES and EB
are exposures needed to produce the film densities of DS
and DB.
Very often, a special term called latitude is also cited
for film photographic characteristics. The latitude is
usually defined as the exposure range that produces a
certain density range over which a usable image can be
made on film (20). If this density range is between the
upper and lower optical density limits on an image, then
the corresponding exposure range is also called the
SCREEN-FILM SYSTEMS
100
144
2.5
80
X-Omat K film
2
60
1.5
X-Omatic
regular
screen
40
20
0.5
0
300
350
400
450
500
550
600
650
Wavelength (nm)
Figure 9. Relative spectral match of Kodak X-Omat K film
with ultraviolet (UV) and blue-emitting screens. (Courtesy of
Dr. R. Dickerson of Eastman Kodak Company.)
SCREEN-FILM SYSTEMS
Speed Class
<100
100
200400
800
Resolving
Power, lpmm1
100
1015
810
68
46
145
146
SCREEN-FILM SYSTEMS
Figure 11. Pictures of the screenfilm cassettes: (a) a doublescreen double-emulsion cassette; (b) a single-screen singleemulsion cassette.
SCREEN-FILM SYSTEMS
the developer. An incompletely fixed film is easily recognized because it has a cloudy appearance. This is a result
of the dispersion of transmitted light by those very small
silver bromide crystals that have not been removed by the
fixer.
Washing the film thoroughly with water is necessary.
Otherwise the chemical residues left on the film will turn
the film into brown as it ages. This is the function of the
water tank after the developer and the fixer.
The last step for film processing is drying. Warm air is
blown over both surfaces of the film when it is transported
by rollers through the drying chamber. Finally, the dried
film is delivered at the drop slot of the automated film
processor.
QUALITY ASSURANCE AND QUALITY CONTROL
(QA/QC) FOR SCREENFILM SYSTEMS
There are many aspects of QA/QC protocols for screenfilm
system maintenance and film processing. We will briefly
discuss several important tests for routine QA/QC in the
clinical environment.
The film processor needs day-to-day quality control in
order to ensure consistent performance. The major concern
in film processing is the instability due to wet chemistry
variation and temperature fluctuation. The film sensitometry is a method to evaluate and monitor the performance
of a film processor on a daily basis. As an important step in
film processor QC, a light sensitometry strip (see Fig. 13) is
made by a sensitometer and charted in the morning before
any patient images are processed. Needed for film sensitometry are a sensitometer, a box of control films that are
identical so that variations among films are negligible,
and a densitometer to measure the film density. In addition, a thermometer is utilized to measure the developer
temperature to ensure the optimal temperature according
to the manufacturers guideline. Three basic concerns for
film sensitometry are (1) the base plus fog; (2) the speed
147
index; (3) the contrast index. The base plus fog is often
measured at an unexposed area of the sensitometry film.
For the speed index, a step is often designated with a midgray film density such as a film density of no less than, but
close to 1.2 O.D. for mammography (19). For the contrast
index, two steps are designated with one step of high film
density, such as a film density 2.20 O.D. and the other of
low film density such as a film density of no less than, but
close to 0.45 O.D. (19). The difference in density between
these two steps is called the contrast index. The aim values
of these three indexes are established over a period such as
5 consecutive days to smooth out normal day-to-day variation at the initial film processor installation or after a
thorough preventative maintenance and calibration on
the film processor. Day-to-day observation compares the
measured indexes with the aim values. Figure 14 demonstrates sensitometric data for a film processor within one
month. Records like these allow the tracking of the performance trends. The purpose is to eliminate problems in
processor performance before those problems affect patient
images. In mammography, 0.10 O.D. variation from the
aim value triggers the action level for further monitoring
and correction, and 0.15 O.D. variation demands immediate corrective actions before patient films can be processed
(19).
There are certain screenfilm cassette maintenance
issues. First, the intensifying screens need to be kept clean.
Artifacts may appear on images in the presence of dust on
the screens. In mammography, screen clean-up is required
at least once a week (19). In general radiography, screens
are recommended to be cleaned at least on a quarterly
basis. The cleaning procedure involves a solution containing an antistatic compound and a detergent. With a soft
lint-free cloth, the screen surface should be wiped very
gently with the solution. Then the cassette should be left
open to air-dry. Another important issue of the screenfilm
cassette maintenance regards screenfilm contact. A good
screenfilm contact is essential to prevent loss of spatial
resolution. A simple method for testing the screenfilm
contact is to image a piece of wire pattern such as a mesh
phantom placed on the top of the cassette. The sharpness of
the wire pattern in all regions of the filmed image should be
examined. If the screenfilm contact is poor in certain
areas, fuzziness or slightly increased density will be
observed at those locations.
Finally, an important routine QA/QC test in a filmbased imaging environment is related to darkroom fog.
The darkroom fog degrades the image quality unnecessarily and should be prevented. Remedies to eliminate darkroom fog are straightforward, involving sealing the
darkroom from light leaks (e.g., the door frame, the film
processor, the film pass-box and any openings into the
room) and following instructions on safelight type, bulb
wattage and safelight positioning (19,25,26). Such easily
preventable problems are often unnoticed or neglected (26).
Therefore, It needs to be emphasized to have the darkroom
fog tested during the initial film processor installation and
monitored thereafter periodically (e.g., semiannually). To
measure the darkroom fog, we may expose a film with a
phantom that would produce a mid-gray film density
when the film is developed (19). In the darkroom before
148
SCREEN-FILM SYSTEMS
SEXUAL INSTRUMENTATION
15. Wayrynen RE. The photographic process. In: Haus AG,
editor. The Physics of Medical Imaging, Recording System
Measurements and Techniques. New York: American Institute of Physics; 1979. p 115.
16. Dickerson R. Fundamental of silver halide film design. In:
Haus AG, editor. Advances in Film Processing Systems
Technology and Quality Control in Medical Imaging. Medical
Physics Publishing; 2000. p 7384.
17. Pizzutiello Jr RJ, Cullinan JE. Introduction to Medical
Radiographic Imaging. Rochester (NY): Kodak Publication
M1-18; 1993. Chapt. 45. p 71122.
18. Mees CEK, James TH. The Theory of the Photographic
Process. New York: Macmillan; 1966. Chapt. 5. p 87119.
19. Mammography Quality Control Manual, by ACR Committee
on Quality Assurance in Mammography chaired by Hendrick
RE, ACR; 1999.
20. Meeson S, Young KC, Rust A, Wallis MG, Cooke J, Ramsdale
ML. Implications of using high contrast mammography
X-ray film-screen combinations. Br J Radiol 2001;74:825
835.
21. Haus AG, Jaskulski SM. The Basics of Film Processing in
Medical Imaging. Medical Physics Publishing; 1997. Chapts.
3, 5, 6.
22. American National Standards Institute: Method for the
Sensitometry of Medical X-Ray Screen-Film-Processing
Systems. New York: (ANSI PH2.43-1982); 1982.
23. Almeida A, Sobol WT, Barnes GT. Characterization of the
reciprocity law failure in three mammography screen-film
systems. Med Phys 1999;26:682688.
24. Widmer JH, Lillie RF. Roller transport processing artifact
diagnosis. In: Haus AG, editor. Film Processing in Medical
Imaging. Medical Physics Publishing; 1993. p 115129.
25. Suleiman OH, Showalter CK, Gross RE, Bunge RE. Radiographic film fog in the darkroom. Radiology 1984;151(1):
237238.
26. Gray JE. Mammography (and radiology?) is still plagued
with poor quality in photographic processing and darkroom
fog. Radiology 1994;191:318319.
See also X-RAYS:
See PIEZOELECTRIC
SENSORS.
SEXUAL INSTRUMENTATION
KIRK A. BRUNSWIG NEWRING
CRISSA DRAPER
WILLIAM ODONOHUE
University of Nevada
Reno, Nevada
INTRODUCTION
From the annals of measurement comes an item of lore on
the origins of measurement, occurring when two male
149
150
SEXUAL INSTRUMENTATION
SEXUAL INSTRUMENTATION
Figure 2. (a) Vaginal plethysmograph featuring a circularly symmetrical source/detector pattern. (b) Automatic baseline offset
circuit. (From Ref. 4 # 1978, IEEE. Figures courtesy of the
authors.)
151
152
SEXUAL INSTRUMENTATION
intromission is painful or impossible) and vulvar vestibulitis (a specific form of vulvar pain). They conclude that
EMG is not a useful method to distinguish between
asymptomatic women and women with partial vaginismus and vulvar vestibulitis. However, other researchers
have found EMG to differentiate women with vaginismus
from those without during basal and induced vaginismus
conditions. Others have used EMG to demonstrate differences between ejaculatory and nonejaculatory orgasmic
women. Electromyography has been used successfully in
several studies researching etiology, treatment, and biofeedback for urinary incontinence. While this approach
appears promising, there does not appear to be a consensus on the utility of this approach relative to other
approaches (e.g., Vulvalgesiometer, discussed below)
(Fig. 3).
Thermistor Clip and Vaginal Temperature. In a series of
studies, Henson et al. (11) tested for a relationship
between labial temperature and subjective ratings of
arousal. They began by developing a thermistor-clip to
measure changes in labial temperature, and found that
labial temperature rose in response to erotic stimuli,
while other measures of body temperature were unaffected. In assessments throughout the sexual arousal
cycle, VPPG data and labial temperature variation were
found to show corresponding variations up to the point of
orgasm. The temperature remained relatively constant
during orgasm, but began to rapidly decrease during the
resolution phase. A follow-up study by another group
using a portable vaginal temperature gauge found variation in vaginal temperature over the course of the day.
These researchers hypothesized that the variations may
be concomitant with circadian temperature changes, with
temperature decrease in arousal being perhaps related to
vaginal wall edema or a change in the position of the
uterus. While Henson and colleagues made strong arguments for the use of temperature as a meaningful measure, later researchers have not followed-up on their early
works.
SEXUAL INSTRUMENTATION
153
Imaging
Duplex Doppler Ultrasonography. Munarriz et al. (14)
reported on the use of duplex doppler ultrasonography
(DDU) to assess genital engorgement. They used ultrasonography combined with the Doppler effect to assess
clitoral and corpus spongiosum diameter, as well as clitoral
and corpus spongiosum peak systolic and end-diastolic
velocity. The Doppler effect can show whether blood is
flowing toward or away from the device, while the ultrasound helps for visualization. They concluded the use of
ultrasonography appears to be a less invasive and a
consumer-friendly approach to assess genital engorgement
in comparison with VPPG. Others have used DDU to assess
changes in clitoral engorgement in a study of Alprostadil.
Relative to other approaches, such as self-report, DDU is
more time and cost-intensive and less invasive than VPPG.
Magnetic Resonance Imaging. Rosen (15) reports on the
promising developments in the use of magnetic resonance
imaging (MRI) to assess genital engorgement and response
in human sexuality. However, there are few published
studies in this promising area in the assessment of human
female sexuality. Like the DDU, it is anticipated that
with additional research, the MRI will be rated as more
consumer-friendly than VPPG, and will likely be more costintensive than self-report measures of sexual arousal and
genital engorgement.
154
SEXUAL INSTRUMENTATION
SEXUAL INSTRUMENTATION
Table 1. Female Sexual Behavior Assessment
Device
Function
VPPG
Measures changes
in blood volume
Tests for vaginismus
and vulvar vestibulitis
Measures labial temperature
Measures pain associated
with vulvar vestibulitis
syndrome
Measures genital engorgement
Measures genital engorgement
Treats vaginismus
Increase genital engorgement
2,5
Treats dysmenorrhea
24
EMG
Thermistor clip
Vulvalgesiometer
DDU
MRI
Vaginal dilators
Clitoral Vacuum
(EROS therapy)
IUD with danazol
References
10
11
12
14
15
16
20
155
relaxation and meditation. Many of the more recent treatment outcome studies limit their dependent measures to
self-report, often ignoring the physiological assessment
that some researchers see as necessary and vital. Beck
(25) reviewed the theories of etiology, prevalence estimates, and theories related to hypoactive sexual desire
disorder. She concluded that a lack of valid, reliable, and
consumer-satisfactory dependent measures impede scientific progress in this area.
Self-Report. For a review of self-report measures of
female sexual function and behavior, please refer to Althof
et al. (26) (Table 1).
INSTRUMENTS AND MEASUREMENT OF MALE HUMAN
SEXUAL BEHAVIOR
Erectile Dysfunction and Sexual Deviance
The measurements of and devices related to male sexual
behavior typically fall into one of two categories: erectile
dysfunction and deviant sexual arousal. Coleman (27)
reviews the scientific literature on the etiology and intervention for Erectile Dysfunction (ED), which is defined as
the persistent inability to achieve or maintain an erection
sufficient for satisfactory sexual activity. It is estimated
that > 50% of men of 65 years-of-age experience ED. Meuleman and Van Lankveld (28) note that with the increasing
availability of pharmacological interventions for ED, male
hypoactive sexual desire disorder may be commonly misdiagnosed. They conclude, HSDD is more common in men
than in women. In public opinion and in medical practice,
HSDD is often misinterpreted as ED, and treated as such.
There is a need for physicians and patients to be educated,
and for the development of reliable clinical tools to assess
this aspect of male sexual function (294). The tools used
for the assessment and treatment of ED are described
below.
The second area of assessment and intervention is
toward deviant sexual interest and arousal: most notably,
pedophilia. For the assessment of sexual interest, researchers have often turned away from face-valid self-reports and
Figure 7. Barlow-type strain gage for monitoring penile tumescence. (Courtesy of Farrall Instruments, Inc., Grand Island, NE.)
156
SEXUAL INSTRUMENTATION
SEXUAL INSTRUMENTATION
157
gumming adhesive. Moreover, while this is relatively inexpensive, the published reports provide two false positives
and one false negative in a rather small sample.
Electromyography. Da Silva et al. (35) found that EMG
could be useful in the differential diagnosis of ED. In this
clinician-administered procedure, EMG inserts electrode
needles into the muscle, and when the subject is asked to
move that muscle, the EMG gives a general picture of the
muscle activity by showing the action potentials occurring
in the specific surrounding muscle cells. This makes it
possible to see whether the dysfunction is indeed physiological. However, few researchers have completed followup studies on this promising work.
Imaging
Near-Infrared Spectroscopy. Burnett et al. (36) compared near-infrared spectroscopy (NIS) with color duplex
ultrasonography, Strain Gauge circumference measure,
158
SEXUAL INSTRUMENTATION
Figure 10. The vacuum constrictive device (VCD) sucks air out of
a cylinder to increase penile engorgement.
SEXUAL INSTRUMENTATION
Table 2. Erectile Dysfunction
Device
Function
Snap Gauge
Strain Gauge
EMG
NIS
VCD
Penile
Prosthetics
Reference
32
34
35
36
39
leakage, breakage, infection, and stretching due to overuse. A common partner complaint is the lack of girth; other
complaints have included spontaneous deflation, a cold
penis, and that intercourse felt unnatural. Malleable
implants are reputed to be easier to install, with inflatable
prosthetics typically rated higher by consumers and their
partners (Table 2).
Summary. Several researchers have explored the
effectiveness, advantages and disadvantages of pharmacological, psychotherapeutic, surgical, and mechanical treatment of ED, and in combinations of these. Taken together,
there is no clear gold standard for the treatment of ED;
rather, there are several tools available to the clinician and
consumer that may be appropriate given the clients physiology, psychology, and context.
DEVIANT PHYSIOLOGICAL AROUSAL
Assessment
The second major area of inquiry into male sexual behavior
relates to physiological changes related to deviant sexual
arousal. The following section describes the use of the
penile plethysmograph (PPG), visual tracking (VT), and
pupillometry (PM) to assess differential arousal in
response to presentation of varied stimuli. The bulk of this
work centers on deviant sexual arousal, typically with
adult males being shown or presented videotapes, still
images, or audio recordings. The stimuli typically depict
age-appropriate as well as age-inappropriate stimuli, and
may include other challenges, such as sadistic themes,
adult rape themes, fetishes, bondage or sadomasochistic
themes, or both, and control conditions with no intended
sexual content.
While in Freunds early phallometry work (41) PPG
typically assessed volume, the bulk of the last halfcenturys research using PPG seems to be reliant upon
circumferential assessment. Bancroft et al. (42) describe
the construction, provide schematics, and a photograph of a
simple transducer for measuring penile tumescence. The
device is a mercury and rubber strain gauge, which they
describe is inexpensive, portable, easy to apply, and unobtrusive in use. They contrast the simple strain gauge
with the more complex volumetric PPG used by Freund
159
160
SEXUAL INSTRUMENTATION
SEXUAL INSTRUMENTATION
161
Function
PPG
Measures circumference
changes with different stimuli
Tracks pupil dilation
with different stimuli
Tracks visual tracking with
different stimuli
Assesses sexual arousal stimuli
Measures skin response
with different stimuli
Measures subtle physiological
changes associated with lying
Pupillometry
Abel Screen
EEG Movement
GSR
Polygraphy
Reference
43
59
56
57
162
SEXUAL INSTRUMENTATION
BIBLIOGRAPHY
1. Semmlow JL. Sexual instrumentation. In: Webster JG, editor. Encyclopedia of Medical Devices and Instrumentation.
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2. Hatch JP. Vaginal photoplethysmography: Methodological
considerations. Arch Sexual Behav 1979;8(4):357374.
3. Sintchak G, Geer JH. A vaginal plethysmography system.
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4. Ormon H, Weinnian J, Weinstcin D. A vaginal photoplethysmography transdueer. IEEE Trans Biomed Eng BME 1978;
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5. Hoon PW, William D, Laughter JS. Infrared vaginal photoplethysmography: Construction, calibration, and sources of
artifact. Behav Assess 1984;6(2):141152.
6. Geer JH, Morokoff P, Greenwood P. Sexual arousal
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7. Van Dam FS, Honnebier WJ, van Zalinge EA, Barendregt JT.
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8. Beck JG, Sakheim DK, Barlow DH. Operating characteristics
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its use. Arch Sexual Behav 1983;12(1):4358.
9. Lawrence A, Latty E, Chivers M, Bailey J. Measurement of
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10. Engman M, Lindehammer H, Wijma B. Surface electromyography diagnostics in women with partial vaginismus with or
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Psychosomat Obs Gyn 2004;25(34):281294.
11. Henson DE, Rubin HB, Henson C. Labial and vaginal blood
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12. Pukall C, Binik YM, Khalif S. A new instrument for pain
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13. Levin RJ. A journey through two lumens. Inter J Impot Res
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14. Munarriz R, et al. A prospective duplex doppler ultrasonographic study in women with sexual arousal disorder to
objectively assess genital engorgement induced by EROS
Therapy. J Sex Marital Ther 2003;29(Special Issue): The
Annual Meeting of the Female Sexual Function Forum:
8594.
SHOCK, TREATMENT OF
38. Kalmus E, Beech AR. Forensic assessment of sexual interest:
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39. Wylie KR, Steward D, A Homemade Device for Erectile
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Accessed
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41. Freund K, Charles U. A laboratory method for diagnosing
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42. Bancroft JJJ, Jones HG, Pullan BR. A simple transducer
for measuring penile erection, with comments on its use in
the treatment of sexual disorders. Behav Res Ther 1966;4:
239241.
43. ODonohue W, Letourneau EY. The psychometric properties
of the penile tumescence assessment of child molesters.
J Psychopathol Behav Assess 1992;15(3):259274.
44. Golde JA, Strassberg DS, Turner CM, Psychophysiologic
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45. Rosen RC, Kopel SA. Penile plethysmography and biofeedback in the treatment of a transvestite-exhibitionist.
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46. Haywood TW, Grossman LS, Cavanaugh JL. Subjective versus objective measurements of deviant sexual arousal in
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1990;2(3):269275.
47. Rea JA, DeBriere T, Butler K, Saunders KJ. An analysis of
four sexual offenders arousal in the natural environment
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Abuse: J Res Treatment 1998;10(3):239255.
48. Mathews C, Hartsell JE, Kohn M. Debunking penile plethysmograph evidence. Reporter 2001;28(2):1114.
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50. Abel GG, et al. Screening tests for pedophilia. Criminal
Justice Behav 1994;21(1): Special issue: The assessment
and treatment of sex offenders 115131.
51. Laws RD, Gress CLZ. Seeing things differently: The viewing
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52. Glasgow DV, Osborne A, Croxen J. An assessment tool for
investigating paedophile sexual interest using viewing time:
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53. Gaither GA. The reliability and validity of three new measures of male sexual preferences. Dissertation Abs Inter: Sec
B: Sci Eng 2001;61(9-B):4981.
54. Web brochure. (No date) Abel Assessment for Sexual Interest
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arousal and interest: Visual reaction time and penile
plethysmography. Sexual Abuse: J Res Treat 2002;14(3):
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56. Cohen AS, Rosen RC, Goldstein L. EEG hemispheric asymmetry during sexual arousal: Psychophysiological patterns
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163
58. Sbraga TP. Sexual deviance and forensic psychology: A Primer. In: ODonohue W, Levensky ER, editors. Handbook of
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59. Abel, Saether 2001.
See also ANALYTICAL METHODS, AUTOMATED; PERIPHERAL VASCULAR NONINVASIVE MEASUREMENTS; STRAIN GAGE; TEMPERATURE MONITORING.
SHOCK, TREATMENT OF
SABIN DECAU
COLIN F. MACKENZIE
University of Maryland,
School of Medicine
Baltimore, Maryland
INTRODUCTION
Assessment and treatment of shock is based on understanding of circulatory system physiology and cellular
metabolism. Shock is defined as inadequate supply of oxygen and nutrients due to inadequate capillary perfusion to
the cells. This definition is not always correct, as in severe
shock some cells cannot metabolize oxygen even with
adequate perfusion. In addition, the removal of metabolites
is equally important or even more crucial over time, since
accumulated metabolites will cause cell injury.
Deficient capillary perfusion triggers a host of metabolic
changes in every organ and tissue, which affects whole
body homeostasis and circulation. Ideally, one should evaluate the cellular metabolism, but this assessment can be
done only indirectly by measuring the acidbase balance in
the form of blood gas and pH. This arterial or venous blood
test does not give any information about the regional
metabolic alterations. For evaluation of the circulatory
function, indirect measurements are used including heart
rate, blood pressure, and urinary output. Invasive hemodynamic monitoring devices, such as the pulmonary artery
catheter are also used for cardiac function assessment. To
effectively reverse shock requires monitoring of the pathophysiologic state of hypoperfusion. Various devices are
used for this state to be monitored directly or indirectly,
continuously and intermittently, so that the patient
response to therapy can be determined and treatment
adjustments made.
ETIOLOGY
There are three common types of shock: loss of blood
volume (hypovolemic shock), abnormal blood distribution
(e.g., septic shock), and cardiac pump failure (e.g., cardiogenic shock). In practice, these three types of shock do not
occur independently, but are frequently mixed with a
similar final pathway, irrespective of the circulatory or
cardiac state that may have been the precipitant (1).
164
SHOCK, TREATMENT OF
Heart
The critical event in the development of cardiogenic shock
is severe impairment of heart muscle contractile performance. Cardiac performance is primarily determined by
four factors: preload, afterload, strength of contraction, and
heart rate. Preload is defined as the force exerted on
myocardium at the end of ventricular filling. If the filling
is inadequate (low preload), cardiac output will be reduced.
This finding is best exemplified by extracardiac obstruction, such as pericardial tamponade (blood in the pericardial sac that surrounds the heart) or by the reduction of
venous return to the heart caused by high thoracic pressure (such as occurs with a pneumothorax, which is air
under tension between the ribs and lung). Afterload is the
resistance to emptying of the ventricles with myocardial
contraction after the opening of the pulmonary and aortic
valves. A rapid increase in afterload as in valvular stenosis
leads to decreased volume of blood ejected from ventricles
and decreased cardiac output. Contractility is most
affected by loss of heart muscle as a result of myocardial
infarction (heart attack). In the acute setting of myocardial
ischemia, loss of at least 40% of left ventricular heart
muscle results in severe depression of cardiac performance
and shock.
A similar picture may also result from myocarditis (an
inflammation of the heart muscle) and with prolonged
cardiopulmonary bypass during cardiac surgery. In addition, myocardial stunning may occur following reversible
myocardial ischemia. If the heart rate is too fast as in
ventricular dysrhythmias, this may compromise ventricular filling and decrease cardiac output. If the rate is too
slow, cardiac output may be insufficient, and shock may
ensue. Both high and low heart rates are common complications of myocardial infarction (13).
Loss of Volume
Hypovolemic shock is caused by a reduction in intravascular circulating volume to a point where compensation is
no longer possible, by constriction of venous capacitance
vessels, to maintain cardiac filling. The loss of circulating
volume may result from hemorrhage, dehydration, or leakage from the circulation into the body tissues. Trauma and
gastrointestinal bleeding are common causes of rapid blood
loss and lead to a reduction in preload and cardiac output.
However, the oxygen (O2) carrying capacity of blood is not
severely impaired except in massive blood loss causing a
decrease in hemoglobin concentration. Dehydration results
in intravascular volume reduction with an increase in O2
carrying capacity, since the number of red blood cells per
unit of volume will increase, but the cardiac output is
decreased.
Abnormal Distribution
Maldistribution of blood flow occurs with widespread vasodilation usually caused by infectious agents (septic shock)
but vasodilation with low systemic vascular resistance may
be caused by other mechanisms including endocrine disease, anaphylaxis (severe systemic allergic reaction), and
neurogenic shock.
PATHOPHYSIOLOGY
The underlying result of shock of any etiology is hypoperfusion at the cellular level due to an inability to provide the
cell with adequate oxygen, glucose, and other nutrients
necessary to maintain normal functions. Consumption
is calculated by the Fick equation, where cardiac output O2 consumption % (arterial-mixed venous O2 content). If the cardiac output is low, the tissue blood flow is
reduced.
Hypoperfusion and hypovolemia due to blood loss
decrease the blood pressure and cardiac output. With
the loss of up to 15% of total blood volume, no detectable
changes in heart rate and blood pressure may be
found because venous capacitance vessel constriction compensates for hypovolemia and maintains cardiac filling
pressures. If fluid loss is 1530% of blood volume, that is,
7501500 mL in a 70 kg male, heart rate will increase
tending to maintain cardiac output. Pulse pressure (the
difference between systolic and diastolic blood pressure)
decreases due to a rise in vascular resistance mediated by
circulating catecholamines. The systemic vascular resistance (SVR) increases by constriction of arterioles, which
tends to maintain an adequate arterial pressure. However, an increase in SVR raises arterial pressure, but
unless it is accompanied by an increase in cardiac output,
it has no effect on tissue blood flow. The relationship
between flow and pressure is as follows: flow pressure/
resistance, and can be applied to the entire circulatory
system, or to a single organ or even an electric circuit
(Ohms law).
If the heart produces a constant flow per unit time
(cardiac output), then the tissue blood flow (perfusion)
will be inversely proportional to the vascular resistance.
Therefore, in the case of shock, capillary perfusion should
be globally reduced. However, this is not the case, as
different organs have variable blood flow and oxygen
utilization. The kidneys have high blood flow and little
O2 extraction, whereas the heart has relatively low blood
flow (because it is contracting) and high O2 extraction
(Fig. 1) (4). In shock, vasoconstriction occurs preferentially in certain regions (skin, muscle, viscera), diverting
the blood flow from these high vascular resistance organs
to more vital organs with low resistance, such as heart
and brain. If blood loss continues beyond 3040% of total
blood volume, the compensatory mechanisms fail and the
blood pressure will fall, accompanied by marked tachycardia, changes in mental status, and decreased urinary
output (1).
In the first stage of shock, arterioles are constricted and
the amount of oxygen available to tissues may be insufficient for their metabolic needs. The global oxygen
consumption will decrease after O2 extraction from hemoglobin has been maximized (from a normal of 25% of the O2
carriage to up to 70%). When O2 consumption falls below a
critical level, local metabolism becomes anaerobic, which
leads to an increased production of lactic acid by the cells.
Later on, this metabolic acidosis causes relaxation of the
precapillary sphincters while the postcapillary venules
are still constricted. Therefore, the capillaries become
overfilled with blood and the hydrostatic pressure
SHOCK, TREATMENT OF
Venous saturation
Jugular vein O 2
Sat ~ 50%
Pulmonary artery
S iO2 ~ 75%
Jugular vein
Brain
Carotid artery
Pulmonary
artery
Aorta
Coronary
Coronary sinus
O2 sat ~~ 30%
Blood flow
Cerebral blood
Flow ~ 750 mL/min
(12 20% Q t)
Total blood flow
(Q t, cardiac output)
~ 6000 mL/min
Heart
Coronary blood flow
~ 225 mL/min (5% Q t)
Sinus
Liver
Skin venous O2
Sat variable
Spleen
Mesentery
Renal vein O2
Sat ~ 95%
165
Right kidney
Skin
Left kidney
SHOCK ASSESSMENT
Renal blood flow
~ 1200 mL/min
(20 25% Q t)
166
SHOCK, TREATMENT OF
64
60
56
52
48
44
40
36
32
28
24
20
16
12
8
4
0
4
64
60
56
52
48
44
40
36
32
28
24
20
16
12
8
4
0
4
8
12
16
20
24
28
Arterial lactate
r = 0.45
4 0 4 8 12 16 20 24 28 32 36 40
60
56
52
48
44
40
36
32
28
24
20
16
12
8
4
0
4
Heart rate
r = 0.36
4 0 4 8 12 16 20 24 28 32 36 40
Hemoglobin
r = 0.56
76
72
68
64
60
56
52
48
44
40
36
32
28
24
20
16
12
8
4
0
4
8
Mixed-venous Pco2
56
r = 0.13
52
48
44
40
36
32
28
24
20
16
12
8
4
0
4
8
4 0 4 8 12 16 20 24 28 32 36 40
Figure 2. Commonly used clinical and laboratory values compared to quantity of acute hemorrhage. Graphs show predicted
versus actual blood volume reductions for six representative parameters. Solid black lines represent an individual animal (n 10).
Gray bar represents the ideal in which predictions equal actual
blood volume reductions. For mean arterial pressure, predictions
at large volume hemorrhage were more accurate than predictions
with small volume bleeds. Models such as heart rate and lactate
both showed significance variability before hemorrhage among
animals and flat slopes (e.g., mixed-venous PCO2) indicated fixed-volume predictions regardless of actual degree of hemorrhage.
(Reproduced with permission from Waisman Y et al. J. Appl.
Physiol. 1993;74:410519.)
+8
Outcome 1
+7
+6
Cardic
filling
pressure
mmHg
+5
+4
+3
Outcome 2
3A
+2
+1
0
3B
Outcome 3
250 ml infusion
1
2
3
Outcome 4
5 min
Time
10 min
SHOCK, TREATMENT OF
167
HCO
3 =a tonometer pCO2 , where a is the solubility of
CO2 in plasma (a 0.03) Values of pHi <7.32 define mucosal hypoperfusion and are associated with high mortality
rates (10).
Brain Perfusion
Brain perfusion monitoring is technically difficult and
inaccurate. Clinically, signs of confusion, altered sensorium, agitation, and decreased consciousness give a rough
idea about cerebral hypoperfusion. Jugular venous oxygen
saturation (SjvO2), transcranial cerebral oximetry, and
brain tissue oxygen tension (PbtO2) monitoring are the
methods of monitoring brain oxygenation. Measurement
of SjvO2 is performed using a catheter inserted in the
jugular bulb, the upper part of the internal jugular vein.
Continuous monitoring of venous saturation without
blood sampling is possible by using intravenous oximetry.
This type of device has been used in patients with head
injury and during anesthesia for neurosurgery. It provides
only global brain oxygenation monitoring and is susceptible to errors. Cerebral oximeters using near-infrared
spectroscopy seem to be a promising alternative. They
can evaluate regional ischemia, hemoglobin saturation,
and even concentration of oxygenated and reduced hemoglobin. However, these monitors can only assess trends,
where each patient is their own control. There are no
normative data for comparison and the boundaries of
monitored brain tissue cannot be precisely defined. Brain
tissue oxygen tension is measured with small catheters
inserted directly into the brain tissue during a craniotomy
or via a burr hole. These catheters measure pO2, pCO2, pH,
and temperature. Some studies suggest a normal value for
PbtO2 of 35 mmHg, whereas cerebral ischemia is usually
defined as a PbtO2 < 8 mmHg. These data were obtained in
patients with traumatic brain injury, but their usefulness
should be confirmed by further studies (11,12). Extra
cellular glutamate and aspartate measures (obtained by
microdialysis) are closely related to outcome after head
injury (13). These markers were also related to the type of
head injury and suggest that excitatory amino acids play a
role in the evolution of brain injury.
SHOCK MANAGEMENT
Treatment of shock should be directed to its underlying
cause. However, establishing an exact diagnosis can be
168
SHOCK, TREATMENT OF
time consuming, so management is focused on simultaneously stabilizing the patient and proceeding with diagnostic tests to identify the cause of shock.
For cardiogenic shock, the goal is an increase in cardiac
output by acting to change preload, afterload, contractility,
or heart rate. Therapy is tailored using information provided by a PA catheter. Various drugs are given to increase
contractility and to relieve pulmonary congestion. In unresponsive cases, additional measures may be considered,
such as urgent myocardial revascularization in acute myocardial infarction, intraaortic balloon counterpulsation,
and anatomic defects repair (ruptured valves). In extracardiac compression, relieving the pressure of pericardial
tamponade by pericardial puncture or insertion of a chest
tube for increased intrathoracic pressure due to pneumothorax is the treatment of choice, when these are the
causes of impaired cardiac filling and decreased cardiac
output.
In case of septic shock (the most common form of distributive shock), large quantities of fluids are administered
to fill the vascular bed and maintain perfusion pressure.
Cardioactive drugs are used only if cardiac output declines.
At the same time steps are taken to identify and control the
source of infection (3).
Hypovolemic shock requires initial rapid expansion of
circulating volume. Fluid resuscitation is initiated with
administration of crystalloid or colloid solutions through
large-bore intravenous lines. Rapid infusion devices can be
used to pump large amounts of fluids in <10 min. A
potential adverse effect resulting from resuscitation with
large amounts of fluid, when using rapid infusion devices,
is a drop in body core temperature. Levels <35 8C are
associated with impaired coagulation and depressed cardiac contractility (14). Covering the patient with inflatable
warming blankets can prevent this complication, but the
most effective method for rewarming is an extracorporeal
countercurrent warmer through femoral artery and vein
cannulation, which can elevate temperature 6 8C in
<30 min. During fluid infusion, hemodynamic parameters
are continuously monitored and signs of instability (persistent SBP <90 mmHg) imply there is ongoing blood loss
or shock has not been reversed. Classically, a hemoglobin
(Hb) level <10 g/dL with continuous loss requires blood
transfusion, but recent studies have demonstrated that
this level can be as low as 7 g/dL without adverse effects
in the majority of the population (15). Those with cardiac or
cerebrovascular disease should be transfused at higher
hemoglobin concentrations.
provide many future treatment and diagnostic opportunities. Genomics may identify some individuals or disease
states susceptible to adverse outcomes from shock. These
future findings could lead to improved outcome, particularly from septic shock, which has a high mortality and
morbidity.
BIBLIOGRAPHY
1. Kelman GR. Applied Cardiovascular Physiology. London:
Butterworths; 1977.
2. Hardaway G. Shock. The Reversible Stage of Dying. Littleton: KPGS Publishing Company; 1988.
3. Shoemaker WC, Appel PL, Kram HB. Role of oxygen transport in the pathophysiology, prediction of outcome and therapy of shock. In: Bryan-Brown CW, Ayres SM, editors.
Oxygen Transport and Utilization. The Society of Critical
Care Medicine 1987. p 6592.
4. Mackenzie CF. Anesthesia in the shocked patient. J Eur
Emer 1994;4:163172.
5. Shin B, Mackenzie CF, Helrich M. Creatinine clearance for
early detection of post-traumatic dysfunction. Anesthesiology
1986;64:605609.
6. Waisman Y, Eichacker PO, Banks SM, Hoffman WD, MacVittie TJ, Natanson C. Acute hemorrhage in dogs: construction and validation of models to quantify blood loss. J Appl
Physiol 1993;74(2):5109.
7. Mackenzie CF, Shin B, Krishnaprasad D, Illingworth W.
Assessment of cardiac and repiratory function during surgery
on patients with acute quadriplegia. J Neurosurg 1985;62:
843849.
8. Darovic GO. Hemodynamic Monitoring: Invasive and Noninvasive Clinical Application. Philadelphia: WB Saunders;
1995.
9. Weil MH, Nakagawa Y, Tang W, Sato Y, Ercoli F, Finegan R,
Grayman G, Bisera J. Sublingual. capnometry: a new noninvasive measurement of diagnosis and quantitation of severity of circulatory shock. Crit Care Med 1999;27(7):1225
1230.
10. Gutierrez G. Gastrointestinal Tonometry. Oxford Textbook
of Critical Care. Oxford: Oxford University Press;
1999.
11. Symthe PR, Samra SK. Monitors of cerebral oxygenation.
Anesth Clin N Am 2002;20(2):293313.
12. Valadka AB, Gopinath SP, Contant CF. Relationships of
brain tissue PO2 to outcome after severe head injury. Crit
Care Med 1998;26:15761581.
13. Gopinath SP, Valadka AB, Goodman JC, Robertson
CS. Extracellular glutamate and aspartate in head
injuried patients. Acta Neurochir Suppl 2000;76:437
438.
14. Dunham CM, Belzberg H, Lyles R, Weireter L, Skurdal D,
Sullivan G, Esposito T, Hamini M. Resuscitation of hypovolemic traumic patients. Resuscitation 1991;Apr 21(23),
207229.
15. Herbert PC, Wells G, Blajchman MA. A multicenter randomized controlled clinical trial of transfusion requirements in
critical care. N Eng J Med 1999;340:409417.
See also BLOOD
169
Epidermis
HYDROCEPHALUS,
See
PHOTON EMISSION.
The outer thinner layer known as the epidermis is composed mainly of epithelial cells or keratinocytes (13). The
deepest epidermal cells are immature cells and are continually dividing and migrating toward the surface, to
replace lost surface cells; keratinocytes. The same types
of regenerating epidermal cells are found in hair follicles
and other skin appendages, which are anchored in the
dermis. As the cells mature and migrate to the surface,
they form keratin, which becomes an effective barrier to
environmental hazards such as infection and excess water
evaporation.
INTRODUCTION
A body burn is a complex injury process resulting in local
changes in skin integrity as well as profound systemic
changes in fluid and electrolyte balance, metabolism,
and immune defenses. Severe psychosocial changes also
occur in addition to long-term, often permanent changes in
skin function. Major advances in care have resulted in a
marked decrease in mortality and also morbidity, especially with massive burns. In addition to survival, the
current focus in burn care is on improving the long-term
function and appearance of the healed or replaced skin
cover as well as quality of life.
This focus on quality has generated a significant interest in the use of skin substitutes to be used to improve
wound healing, to control pain, to more rapidly close a burn
wound, to improve functional and cosmetic outcome, and,
in the case of massive burns, to increase survival.
To more effectively address these new roles, the new
generation of skin substitutes are developed to be biologically active. The concept behind providing bioactivity is
that the wound healing process can be substantially
improved as compared with a simple synthetic barrier-type
dressing. It remains to be seen just how much better this
new generation of products will impact the burn wound. To
date, the new products to be discussed have not displaced
the more inert standard burn wound dressings, but rather
are used in conjunction and for quite specific indications.
The skin substitutes are initially classified according to
whether they are to be used as a temporary wound covering to
decrease pain and augment healing or a permanent skin
substitute to add to or replace the remaining skin components.
The ideal properties and indications for these products
will be better clarified after a discussion of the function of
normal skin and the effect of a burn on skin integrity.
THE NORMAL PROPERTIES OF SKIN
Normal skin is a very complex bilayer organ with a wide
variety of properties mainly protective barriers, which are
critical to survival (15). Loss of these protective barrier
functions occurs with a skin burn. Restoration of skin
structure and function become the necessary properties
Stratum Corneum. The otnatum corneum is the outermost layer of the epidermis consisting of several flattened
layers of dead keratinocytes as well as keratin. This layer
protects against entry of bacteria and toxins. The epidermal layer regenerates every 23 weeks, but regeneration
requires the structure and functional components of the
dermis.
Skin Functions: Epidermis (Outer Layer).
Protection from drying.
Protection from bacterial entry (infection).
Protection from toxin absorption, like chemicals on
the skin.
Fluid balance: avoiding excess evaporative water loss
that would cause dehydration.
Neurosensory (touch, pain, pressure, sensation).
Social-interactive (visible portion of the body covering).
170
factors and cell signals found in the dermis (6). The dermal
signals are richest in the upper third of the dermis known
as the papillary dermis. The deeper dermal layer is less
able to regenerate epidermis and itself, therefore the thinner the thickness of remaining dermis in a wound, the less
likely it is that the skin can regenerate. More scar will
develop to replace the lost skin. If the dermis is totally
destroyed, a burn cannot heal by itself and a skin graft or
permanent skin substitute is required.
Of extreme importance is the psychological impact in
the quality of healed or replaced skin, as this organ has a
major role in human communication and helps define the
individual. One of the key objectives, of the newer skin substitutes, is to restore some normalcy to the new skin cover.
1st Burn
Epidermis
Superficial
Dermal
2nd Burn
Dermis
3rd Burn
Fat
Deep
dermal
Full
thickness
171
Table 1. Mean Survival Rate after Burns in Burn Centers,a age versus Burn Size
Age (years)
Burn size, % of total skinb
010
1020
2030
3040
4050
5060
6070
7080
8090
90100
01
>95
>95
>90
75
50
50
40
35
30
20
24
>95
>90
>90
80
65
60
50
40
35
20
534
>95
>95
>90
90
80
70
60
45
30
20
3549
>95
>90
>90
80
60
60
40
30
30
15
5059
>95
>90
>75
70
40
40
25
25
<20
0
6074
>95
>70
50
40
10
<25
<10
0
0
0
>75
90
>60
35
<20
<10
<10
0
0
0
0
Pain is a major problem with superficial burns. Temporary skin substitutes markedly decrease initial pain.
Scarring is a result of loss of a large amount of dermis
and a resulting prolonged wound healing period (1317).
The wound healing process includes an initial inflammation followed by an increase in wound fibroblasts, new
vessels, and epithelial cell proliferation (if the burn is
superficial). By 7 days, the fibroblasts are producing
increased amounts of collagen, which persists until the
wound has healed or is closed. Wound inflammation persists as long as the wound is open.
In superficial burns, epidermal regeneration will be
relatively rapid, if the wound environment is optimized.
The injured dermal elements are usually covered by new
epithelium within 2 weeks if protected from environmental insults. Only modest amounts of collagen are deposited. The wound usually becomes relatively pliable with
time and minimal to no wound contraction is seen. Cosmetically, the superficial second degree burn, which heals
in 2 weeks, results in very minimal to no long-term
scarring (1517).
The histology of the wound bed, however, changes dramatically if it has not been re-epithelialized by 3 weeks, as
would be the case with a deeper dermal burn (1317).
Fibroblasts and macrophages become the predominant
cells. Large numbers of myofibroblasts also enter the
wound. Besides leading to contraction, these cells continue
to deposit large quantities of collagen and glycosaminoglycans. Later, closure of this wound by re-epithelialization or
Cause
Hot liquid, short exposure
Hot liquid, hot grease, or flash
flame with longer exposure
Chemicals, direct contact
with flames
Chemicals, flames, explosion
with very high temperature
Appearance
Pain
Healing
Scar
Severe
Moderate
1014 days
24 weeks
Minimal
Moderate
Dry, white
Minimal
816 weeks
None
Severe, usually
needs skin graft
Mild to severe,
depending on timing
and type of graft
172
These properties are then sought when developing new skin substitutes.
173
Company
Tissue of
Origin
Layers
Category
Human
Skin bank
allograft
Human
cadaver
Epidermis and
dermis
Split thickness
skin
Pig skin
Brennan
xenograft Medical
St. Louis,
MO
Human
On site
amnion
procurement
Oasis
Healthpoint,
LTD San
Antonio, TX
Pig dermis
Dermis
Dermis
Biobrane
Transcyte
Placenta
Amniotic
membrane
Xenograft
Extracellular
wound
matrix from
small intestine
submucosa
Dow Hickam/Bertek
Synthetic
Bilayer product
Pharmaceuticals
with added outer silicone
denatured
Inner nylon
bovine
mesh with
collagen
added collagen
Smith and Nephew
Allogenic
Bilayer product
Wound Management dermis
Outer silicone
Largo, FL
Inner nylon
seeded with
neonatal
fibroblasts
Epidermis
Dermis
Bioactive
Dermal like
Matrix
Synthetic
epidermis
and dermis
Uses
How Supplied
Temporary coverage
Frozen in
of large excised burns rolls of varying
size
Temporary coverage
Frozen or
of partial thickness
refrigerated
and excised burns
in rolls
Same as above
Refrigerator
Superficial burns
Skin graft donor
sites
Chronic wounds
Room temperature
storage
Multiple sizes
3 3.5 cm
7 20 cm
Room temperature
storage 15 20 in.
10 15 cm
5 15 in.
5 5 in.
Frozen in 5 7.5 in.
sheets
Superficial partial
thickness burns,
Temporary cover
of excised burns
Bioactive dermal
Superficial to
matrix components
mid-partial
on synthetic dermis thickness burns
and epidermis
Temporary coverage
of excised burns
a
The names and properties of available temporary skin substitutes, with some biological activity are described. Also listed are the indications of the various
products.
174
Allograft Skin
Advantages
A bilayer skin providing epidermal and dermal properties
Revascularizes maintaining viability for weeks
Dermis incorporates into the wound
Disadvantages
Epidermis will reject
Difficult to obtain and store
Risk of disease transfer
ExpensiveNeed to cryopreserve
Advantages
Acts like biologic barrier of skin
Decreases pain
Easy to apply, remove
Transparent
Disadvantages
Difficult to obtain, prepare and store
Need to change every 2 days
Disintegrates easily
Risk of disease transfer
nonviable state after preservation in glycerol or after lyophilization: however, most existing data describe best
results when it is used in a viable state. The epidermal
component provides a barrier until rejected by the host in
34 weeks. The dermis revascularizes and incorporates.
Homograft, another term for human allograft, can only
be obtained from a tissue bank as strict protocols are
required for harvesting and storage. Donors must be
rigidly screened for potential viral and bacterial disease
to avoid any transmission of disease. The product is in
limited supply and very expensive.
The primary indication for use is to cover a large excised
burn wound until an autogenous skin or a permanent skin
substitute becomes available. Allograft is also used to cover
a wide meshed skin graft, sealing the interstices during the
healing process (Table 7).
Xenografts
Although various animal skins have been used for many
years to provide temporary coverage of wounds, only porcine xenograft is widely used today (33,34) (Table 8). The
epidermis of the porcine xenograft is removed and the split
thickness dermis is provided in rolls. Split-thickness porcine dermis can be used after cryopreservation, or after
glycerol preservation. It effectively provides temporary
coverage of clean wounds such as superficial second degree
burns and donor sites (33,34). Porcine xenograft does not
vascularize, but it will adhere to a clean superficial wound
and can provide excellent pain control while the underlying
Human Amnion
Human amniotic membrane is used in many parts of the
world as a temporary dressing for clean superficial wounds
such as partial-thickness burns, donor sites, and freshly
excised burns (35,36). Amniotic membrane is generally
procured fresh and used after brief refrigerated storage. It
can also be used in a nonviable state after preservation
with glycerol. Amnion does not vascularize but still can
provide effective temporary wound closure. The principal
concern with amnion is the difficulty in screening the
material for viral diseases. The risks of disease transmission must be balanced against the clinical need and the
known characteristics of the donor (Table 9). The primary
indications are the superficial burn and the excised
wound.
Oasis Wound Matrix
This product is made of the submucosa of the porcine small
intestine found between the mucosa and muscularis, in the
wall of the porcine small intestine (37,38). The freeze dried
acellular natural matrix retains its natural collagen and
matrix structure and contains most of the bioactive matrix
proteins found in the human dermis (Table 10).
175
Biobrane
This product is a two-layer membrane (39,40). The outer
epidermal analog is constructed of a thin silicone film with
barrier functions comparable to skin. Small pores present
in silicone allow for exudates removal and has permeability
to topical antibiotics.
The inner dermal analogue is composed of a threedimensional (3D) irregular nylon filament weave upon
which is bonded type I collagen peptides. The surface
binding of inner membrane is potentiated by collagen
fibrin bonds as well as fibrin deposition between the nylon
weave. A thin water layer is maintained at the wound
surface for epidermal cell migration maintaining moist
wound healing. Excellent adherence to the wound significantly decreases pain in the superficial partial thickness
burns. The silicone and nylon weave provides flexibility.
The biobrane is removed once the partial thickness wound
has re-epithelialized or the covered excised burn wound is
ready for grafting. However, if left in place for >2 weeks the
product is difficult to remove as tissue grows into the inner
layer. Biobrane L contains a nylon fabric woven from
monofilament threads that provide a less dense matrix
and less adherence, preferred (e.g., on a donor site). There
is likely very little direct bioactivity from the collagen
peptides (40). The product has a long shelf life and can
be stored at room temperature. It is also relatively inexpensive (Table 11).
The primary indication is for closure of the clean superficial burn or the excised burn wound.
Transcyte
This product is also a bilayer skin substitute (41,42). The
outer epidermal analogue is a thin nonporous silicone film
Table 11. Advantages and Disadvantages of the Use of
BIOBRANE as a Skin Substitute
Biobrane
Advantages
Bilayer analog
Excellent adherence to a superficial burn
Decreases pain
Maintains flexibility
Easy to store with long shelf life
Relatively inexpensive
Disadvantages
Has very little direct bioactivity
Difficult to remove if left in place >2 weeks
with barrier functions comparable to skin. The inner dermal analog is layered with human neonatal foreskin fibroblasts that produce products, mainly collagen type I,
fibronectin, and glycosaminoglycans.
A subsequent cryopreservation destroys the fibroblasts,
but preserves the activity of fibroblast derived products on
the inner surface. These products are then anticipated to
stimulate the wound healing process (Table 12). A thin
water layer is maintained at the wound surface for epidermal cell migration.
The nylon mesh provides flexibility and excellent adherence properties significantly decrease pain in the partial
thickness burn. The product is peeled off after the wound
has re-epithelialized.
The Transcyte must be stored at 70 8C in order to
preserve the bioactivity of the dermal matrix products.
The primary indication is for closure of the clean superficial to mid-dermal burn, especially useful in children.
Transcyte is also indicated for the temporary closure of the
excised wound prior to grafting. Tissue ingrowth tends to
be less of a problem even if the product is kept in place for
>2 weeks.
Permanent Skin Substitutes
The purpose of these products is to replace full thickness
skin loss as well as to improve the quality of the skin, which
has been replaced after a severe burn (2023).
As opposed to the bilayer concept of the ideal temporary
skin substitute, permanent skin replacement is much more
complex.
This area can be arbitrarily divided into two approaches
(2123). The first approach is the use of a bilayer skin
substitute, with the inner layer being incorporated into the
wound as a neodermis, rather than removed like a temporary product. The outer layer is either a synthetic to be
replaced by autograft (epidermis) or actual human epithelial cells. If the outer layer is composed of epithelial cells
that will form epidermis barrier function is not sufficiently
developed at placement to act immediately as an epidermal
barrier.
The second approach is the provision of either just an
epidermal or a dermal analog or simply a coculture of cells
containing elements of both. These products are technically not permanent skin substitutes (Table 13) upon initial
placement as there is no bilayer structure until the product
176
Advantages
Bilayer skin containing human neonatal cells
Not requiring patients skin biopsy
No lag time for production
Contains epidermal and dermal functions (eventually)
Does not need to be frozen
Disadvantages
Made in small pieces and not practical for large burn
Cannot be stored for over 24 h
Relatively expensive
Apligraf
The dermal analog is made of fibroblasts from neonatal
foreskin populated in a bovine type I collagen matrix. This
layer incorporates into the excised full thickness wound
adding a dermal component. Epithelial cells (keratinocytes) are also obtained from neonatal foreskin. No Langerhans cells at present so rejection does not occur. The
epithelial cells divide, migrate and form an epidermis,
which will eventually provide biologic barrier function.
Donor foreskin is screened for viruses, which could be
transmitted. The product is indicated mainly for chronic
wounds. Its use in burns is currently off label (44,45).
Apligraf is typically provided as a 7.5 cm diameter disk
that is 0.75 mm thick. The advantages are that the product
is already made and does not depend on obtaining the
patients own cells (Table 16). However, the product must
be shipped the night before use in a polyethylene bag in
agar nutrient medium and a 10% CO2 content and stored at
room temperature until used (within 24 h).
Table 15. Properties and Uses of the Currently Available Permanent Skin Substitutes
Available Permanent Skin Substitutes
Product
Apligraf
OrCel
Company
Tissue of
Origin
Organogenesis,
Allogenic
Composite
Inc and Novartis
Pharmaceuticals
Corp
Ortec International Allogenic
Inc.
Composite
Epicel
Genzyme Tissue
Repair Corp
Alloderm
Life Cell
Integra
Integra Life
Science Corp
Layers
Category
Uses
Collagen matrix
Composite:
Chronic wounds, often
seeded with human
Epidermis
used with thin STSG
neonatal keratinocytes
and dermis
Excised deep burn
and fibroblasts
Collagen sponge seeded Composite:
Skin graft donor site,
with human neonatal
Epidermis
chronic wounds
keratinocytes and
and Dermis
fibroblasts
Autogenous
Cultured autologous
Epidermis
Deep partial and
keratinocytes
keratinocytes
Only
full thickness
burns >30% TBSA
Allogenic
Acellular Dermis
Dermis only
Deep partial and full
dermis
(processed allograft)
thickness burns, Soft
tissue replacement,
Tissue patches
Synthetic
Silicone outer layer
BioSynthetic Full thickness soft
on collagen GAG
Dermis
tissue defects
dermal matrix
definitive closure
requires skin graft
How supplied
7.5 cm
diameter disk
1/pack
6 6-cm sheets
50 cm2 sheets in
culture medium
1 24 12 cm
2 2 in.
4 10 in.
8 10 in.
5/pack
Orcel
The product is produced as a coculture of keratinocytes and
fibroblasts (neonatal foreskin) in a cross-linked bovine
collagen sponge (46). The donor tissue is screened for
viruses. The nonporous side of the sponge is seeded with
the keratinocytes and the porous side with fibroblasts.
After application, a neodermis forms. Once applied the
epidermis and an epidermal barrier requires 14 days to
develop as the keratinocytes migrate and divide on the
surface (Table 17).
The product is indicated mainly for chronic wounds but
is also indicated for coverage of split thickness skin graft
(STSG) donor sites. This product is not currently indicated
for use on excised burn. The purpose for the STSG is to
provide a better functional and cosmetic outcome compared
to a healed donor site. It is shipped in a package filled with
its culture medium which is stored at room temperature
until used, usually within a few days.
Epicel
This product, used mainly for very large burns is composed
of the patients skin epithelial cells and referred to as
cultured epithelial autograft (CEA). Therefore, only the
epithelial layer is provided (4749). The product is made
from a small biopsy of normal skin (2 2 cm) from the burn
patient. The epithelial cells are extracted and cultured.
Use of a cell culture technique allows the keratinocytes to
be grown in a thin sheet 10,000 times larger than the initial
177
178
6. Raghow R. The role of extracellular matrix in post-inflammatory wound healing and fibrosis. FASEB J 1994;8:823
850.
7. Demling R. Burn care. In: Wilmore D, editor. ACS Surgery.
New York: Web MD; 2002. p 479.
8. Herndon D. Total Burn Care. Philadelphia: WB Saunders;
2002.
9. Neely A, Brown R, Chendening C, et al.Proteolytic activity in
human burn wounds. Wound Rep Regen 1997;5:302309.
10. Muller M, Pegg S, Rule R. Determinants of death following
burn surgery. Br J Surg 2001;88:583587.
11. Komgova R. Burn wound coverage and burn wound closure.
Acta Chir Plast 2000;42:6468.
12. Sheriden R. Management of burn wounds with prompt excision and immediate closure. J Inten Care Med 1994;9:617.
13. Demling R, DeSanti L. Scar management strategies in wound
care. Rehab Manage 2001;14:2632.
14. Spres M, Herndon D, et al. Prediction of mortality from
catastrophic burns in children. Lancet 2003;361:989994.
15. Ladin D, Garner W, Smith D. Excessive scarring as a consequence of healing. Wound Repair Reg 1994;3:614.
16. Scott P, Ghabary A, Chambers M, et al. Biologic basis of
hypertrophic scarring. Adv Struct Biol 1994;3:157165.
17. Erlich HP, Krummell T. Regulation of wound healing from a
connective tissue perspective. Wound Repair Reg 1995;4:
203210.
18. Badylak S. The extracellular matrix as a scaffold for tissue
reconstruction. Cell Develop Biol 2002;13:377383.
19. Jones L, Currie L, Martin R. A guide to biological skin
substitutes. Br J Plast Surg 2002;55(3): 185193.
20. Gallico GG. Biologic skin substitutes. Clin Plast Surg 1990;
512520.
21. Sheridan R, Tompkins R. Alternative wound coverings. In:
Herndon D, editor. Total Burn Care. Philadelphia: WB Saunders; 2003. p 712.
22. Clark R, Folkvard J, Wortz R. Fibronectins, as well as other
extracellular matrix proteins mediate human keratinocytes
adherence. J Invest Dermatol 1985;84:378383.
23. Clore J, Cohan I, Diegelmann R. Quantitation of collagen
types I and III during wound healing. Proc Soc Exper Biol
Med 1979;161:337340.
24. Doillon C, Dunn M, Bender E, et al. Collagen fiber formation
in repair tissue: Development of strength and toughness.
Collagen Relat Res 1985; 481485.
25. Takashima A, Grinnell F. Human keratinocytes adhesion
and phagocytosis. Prompted by fibronectin. J Invest Derm
1984;83:352358.
26. Miller E, Gay S. Collagen structures and function in wound
healing: biochemical and clinical aspects. In: Cohen K, editor.
Philadelphia: Saunders; 1992. p 130.
27. Nowicki CR, Sprenger C. Temporary skin substitutes for
burn patients: a nursing perspective. J Burn Care Rehab
1988;9(2):209215.
28. Shakespeare P. Survey: use of skin substitute materials
in UK burn treatment centers. Burns 2002;28(4):295
297.
29. Smith K, Rennie MJ. Management of burn injuries: A rationale for the use of temporary synthetic substitutes? Prof
Nurse 1991;571574.
30. Bondoc CC, Burke JF. Clinical experience with viable frozen
human skin and a frozen skin bank. Ann Surg 1971;174:371
382.
31. Herndon DN. Perspectives in the use of allograft. J Burn Care
Rehab 1997;18:56.
32. May SR, Still JM Jr., Atkinson WB. Recent developments in
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179
54. Navsaria HA, Ojeh NO, Moiemen N, Griffiths MA, Frame JD.
Re-epithelialization of a full-thickness burn from stem cells of
hair follicles micrografted into a tissue-engineered dermal
template (Integra). Plast Reconstr Surg 2004;113:978981.
55. Frame JD, Still J, Lakhel-LeCoadou A, Carstens MH, Lorenz
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2004;113:13301338.
See also BIOCOMPATIBILITY
180
181
182
cells, in vitro synthesis of organs, and induced regeneration. The last three techniques have been grouped together
and are known by the moniker tissue engineering (20).
All six techniques will be discussed in the following
sections.
Transplantation. Transplantation, the transfer of an
organ or a fraction thereof from a donor to a host, is widely
utilized as a therapeutic strategy to replace complex tissues and organs. Since the introduction of transplantation
in the early twentieth century (21), it has been used in
increasingly complex organ systems such as the skin,
cornea, kidney, liver, lungs, and heart. Patients have
exhibited extraordinary survival characteristics even
with the simultaneous transplantation of multiple organs
(2227).
While transplantation of tissues at a few immune-privileged sites such as the eye and testis can occur without
rejection, the most significant challenge facing modern
transplantation is the immunological barrier for transplantation of tissues from donor to host, where the donor
organ is attacked and rejected by the hosts immune system
upon transplantation; this response is termed host-versusgraft disease where the hosts (patients) immune system
recognizes the antigens expressed on the graft tissue as
foreign and attacks and destroys the tissue. The primary
clinical method for preventing rejection of the transplanted
tissue is the use of drugs to suppress the immune system of
the host. Immunosuppression therapy often is necessary
for the remainder of the hosts life to prevent transplant
rejection; however, immunosuppression also presents a
significant hazard to the host, as the immunosuppressed
host becomes vulnerable to infections (28). Significant
efforts have been mounted to develop technologies that
allow for local rather than whole-body immunosuppression, such as the development of cells that can express a
protein (i.e., Fas ligand) to induce immune cell apoptosis
and the use of natural and synthetic polymers to encapsulate heterologous cells to mask their antigens (24,2831).
The major obstacle in using human donors for transplantation has been the difficulty in finding immunocompatible donors and the shortness of supply of suitable
organs because the supply is greatly exceeded by the
demand (32). A more recent area of research has focused
on developing a transgenic pig model to be used as an
immunocompatible donor for humans for a procedure
known as xenotransplantation. Development of this area
of transplantation has been slowed by evidence that pig
viruses are capable of infecting human cells and producing
unique viral infections in the host (3335).
Autografting. With autografting, the donor and the
recipient are the same individual; a fraction of the tissue
or organ is harvested from an uninjured site and grafted at
the nonfunctional site (25). Autografting offers a technology that removes the danger of organ or tissue rejection due
to a host-versus-graft response, but is relatively limited in
its scope of application. Autografting necessitates the creation of a second wound site (donor site), subjecting the
patient to a second severe trauma. Therefore, autografting
is utilized only when the loss of functionality at the sec-
ondary wound site is outweighed by the loss of functionality or morbidity at the primary wound site. This
procedure is obviously limited by the availability of functional tissue that can be transplanted without additionally
harming the patient. Major clinical uses of autografting
have been associated with skin grafting in massively
burned patients (36), the use of the sural nerve to bridge
a severe peripheral nerve injury, primarily in the case of
hand injuries (3741), and the use of autologous vein graft
to bypass a restricted artery (42).
Permanent Prosthetic Device. The implantation of a permanent prosthetic device to replace the functionality of lost
or damaged tissues offers a number of advantages and
disadvantages. Typical examples of prosthetic devices
are artificial hips and knees (43), cardiac pacemakers
(44), heart valves (45), stents (46), cochlear implants
(47), and contact lenses (48). Prosthetic devices are typically fabricated from biologically inert materials such as
metals, ceramics, and synthetic polymers. Hence, these
devices do not provoke the immune response problems
inherent to transplanted tissues and organs and can also
be manufactured on a mass scale. Even though these
devices are fabricated from bioinert materials, interactions
with the biological environment surrounding the prosthesis lead to a number of unfavorable physical and biological
manifestations. Specific examples of negative biomaterial
tissue interactions are the formation of a thick, fibrous scar
tissue capsule around a silicone breast implant (49,50),
stress-shielding due to the implantation of a relatively stiff
(compared to the host bone) hip prosthesis that eventually
leads to a loss of bone mass (51), platelet aggregation to
implanted surfaces, also known as biofouling (5255), and
the accumulation of polyethylene particles in the lymph
system as a result of wear of an orthopedic implant (56,57).
The spontaneous remodeling process of the surrounding
tissues can also be significantly altered, negatively or
positively, by the presence of the prosthetic device (58).
The often-serious side effects that appear as a result of
interactions between nonbiological materials and the surrounding tissues illustrate the difficulty of replacing bioactive tissues with bioinert materials with drastically
different material and mechanical properties.
Stem Cells. Stem cells present an exciting possibility for
replacement of lost or damaged organs and tissues. The
pluripotential nature of stem cells offers the possibility for
the synthesis of tissues from the least differentiated cells in
the body (59,60). Current efforts in stem cell research have
focused on identifying protocols to harvest stem cells,
expand them in culture, and reimplant them at a site of
injury, as well as to develop technologies to introduce genes
into stem cells so that when reintroduced to the patient,
they will synthesize the required proteins in vivo. Currently, mesenchymal stem cells (61), epithelial stem cells
(62), and neural stem cells (63) have been grown in vitro
and studied. While few advances in the use of stems cells
for replacement of damaged tissues have been made to
this point, stem cell technologies present a new area of
scientific study for future exploration with a great deal of
promise.
183
network (98101). Continued exploration of in vitro techniques to synthesize tissue replacements has been hampered
by the complexity of biological systems and an inability to
provide the proper nutrient cocktails (i.e., cytokines, growth
factors), the structures necessary to deliver these nutrients
(i.e., arteries, veins, and capillary systems), and the correct
mechanical environments (ECM analog structures) for complex tissue and organ growth outside of the organism.
Induced Organ Synthesis In Vivo (Regeneration). Induced
organ synthesis in vivo relies on the healing processes that
are inherently active in a wound site to regenerate lost or
damaged tissue. In this method, an analog of the ECM is
implanted in the wound site and combined with the biological processes in the wound induce synthesis of a physiologic replacement tissue. Induced organ synthesis was first
identified following the development of fabrication techniques that allowed for synthesis of ECM analogs with a welldefined macromolecular structure, specifically controlling
the ECM specific surface, chemical composition, and degradation rate (102106).
The first application of induced organ synthesis was in
the fabrication of an ECM analog able to induce skin regeneration, the dermal regeneration template (DRT). The DRT
showed very high biological activity when implanted into a
full-thickness skin wound and was capable of inducing
regeneration of the underlying dermal layer of skin as well
as the epidermal and basement membrane layers
(3,103,107113). The speed of this regeneration process
was significantly increased when the DRT was further
seeded with autologous keratinocytes prior to implantation
(3,111,112,114116). This technology will be covered in
greater detail later in the article as one of the major tissue
engineering techniques utilized to treat severe skin injuries.
Induction of organ regeneration, first observed in the
study of skin regeneration, has also been observed in other
tissues and organs with the use of other specialized ECM
analogs. Regeneration of peripheral nerves has been
achieved using a tubular device that incorporates an
ECM analog as a filling, known as the nerve regeneration
template (NRT) (1,117120). The long-term morphological
structure and electrophysiological function of nerves
regenerated using the NRT has been observed to be at
the level of an autografted nerve, the current goldstandard for peripheral nerve injury treatment (121,122).
In addition, the DRT was implanted into a conjunctiva
stromal wound model, where induced regeneration of the
conjunctival tissue structure was also observed (123).
In vitro synthesis and induced organ regeneration (in
vivo synthesis) currently constitute an area of study
termed tissue engineering (20). For the remainder of this
article, we will focus on studies on the structure and
function of ECM analogs for use in tissue engineering
and on an overview of the tissue engineering approaches
that have been utilized to treat skin wounds.
Basic Parameters of the Living Environment During
In Vivo Synthesis
The process of in vivo regeneration of lost or damaged
tissue can be modeled as if the entire process was taking
184
place within a bioreactor that is surrounded by a reservoir with constant properties, representing the entire
organism with its complex homeostatic mechanisms. The
bioreactor itself has a defined anatomical and physicochemical environment (environment of the wound site);
parameters include the temperature, the pH, the structure
of a template within the bioreactor, and the flow rate and
composition of the exudate. The flow of exudate entering
the bioreactor starts almost immediately following the
creation of the wound site, while the structure in the
wound bed is provided by implantation of an analog of
the ECM. The ECM analog, and any cells that may be
seeded within, constitutes the exogenous stimulus provided to the wound bed. During the remainder of the
healing process, the reservoir (surrounding organism) is
considered to maintain the bioreactor environment: temperature, pH, as well as cytokines, growth factors, and cells
present in the exudate. While these factors are considered
standardized in a wound bed, it is the ECM analog that
provides the variable structure and ECM components
(proteins) that are critical for inducing regeneration. If
no active ECM analog is present or if its structural features
are changed, the reaction sequence within the bioreactor
is observed to follow almost completely normal repair
processes that result in wound contraction and scar formation. In contrast, when the appropriate ECM analog is
introduced into the bioreactor normal repair mechanisms
are replaced by induced regeneration, also referred to as in
vivo or in situ regeneration (1).
Experimental study of in vivo regeneration is complicated by a lack of reproducibility between different reaction
sites (anatomical sites); unless the wound site is standardized, it will be impossible to accurately study differences
between ECM analogs when implanted into wound models
and results obtained in independent laboratories will not
be statistically significant. Billingham and Medawar
(124,125) introduced the concept of an anatomically constant wound for the study of massive skin injuries. For skin
injury models, the entire thickness of the skin (epidermis,
basement membrane, and dermis) was consistently excised
down to the layer of the underlying muscle and fascia.
Except for edge effects, this model standardized the wound
environment from one animal to another, making it possible to obtain statistically significant results from a study
with several animals. For the remainder of this article, all
animal results that are discussed will be from this wound
model. In clinical cases, the nature of the wounds is different; such issues will be discussed in greater detail later
in this article.
Mammals possess a small, quite limited, ability to
spontaneously regenerate damage inflicted to most of their
tissues and organ systems. The epidermis and basement
membrane in the skin regenerates spontaneously, provided that there remains an intact, underlying dermal
layer (1). In another example, a small, cylindrical defect
(<1 cm in diameter) in mammalian long bones is spontaneously refilled with normal bone (126), and a gap <5 mm
in a transected rat sciatic nerve can be spontaneously
regenerated to a moderate extent (127131). In these cases,
regeneration is observed without the implantation of any
active ECM analog. More specifically in the case of skin
185
td
O1
th
The density of cross-links formed through DHT crosslinking depends on the temperature as well as the length of
exposure, with higher temperatures and longer exposure
lengths producing a higher density of cross-links (104,105).
Ultraviolet (UV) treatment is a second physical cross-linking technique that can create cross-links between collagen
fibers (136138). Additionally, cross-linking can be induced
chemically by introduction of glutaraldehyde (GT) (104) or
with 1-ethyl 3-(3dimenthylaminopropyl)carbodiimide
(EDAC) (139). These chemical cross-linking techniques
are considerably more powerful than the previously noted
physical methods and lead to a much higher cross-link
density and a much longer time constant of degradation
(td). Chemically cross-linked scaffolds must be extensively
washed to remove all trace of the cytotoxic cross-linking
chemicals prior to use in the wound bed; in addition to
concerns regarding washing away the excess chemical,
some chemical cross-linkers function by having all or a
portion of the chemical compound becoming part of the
cross-link. In this case, slow degradation of the scaffold
could result in the release of potentially cytotoxic agents
into the wound site (1,3).
By using both physical and chemical methods, the crosslinking density of a particular collagen or collagenGAG
scaffold can be effectively adjusted to create a wide range of
enzymatic degradation rates. These cross-linking tools can
also be applied to a multitude of other scaffolds, fabricated
from both natural and synthetic materials. As different
wound sites and the same wound sites in different species
have been observed to exhibit very different time constants
for healing (th), it is necessary to adjust the degradation
rate of the ECM analog to the characteristics of the specific
wound bed site and species in order to satisfy the
principle of isomorphic tissue replacement and to induce
regeneration.
CollagenCollagen
P1 COOH P2 NH2 ! P2
NHCO P1 H2 O
CollagenGAG
NHCO GAG H2 O
186
RL2
DC0
individual pore is separated from adjacent pores by membrane like faces while open-cell pore structures exhibit
interconnectivity between adjacent pores. Interconnectivity is critical for cells to be able to migrate through the 3D
structure. The most important structural feature of porous
scaffolds is the relative density (Rd): the density of the
scaffold divided by the density of the solid from which it is
made. The porosity of a scaffold, or pore volume fraction, is
defined as (1 Rd). The relative density defines the amount
of solid material available for cells to bind to; when the
pores are closed or when the relative density is too large,
cells are not able to migrate through the scaffold, a significant impediment for using such a scaffold for a tissue
engineering application. Such structural aspects also suggest that in designing scaffolds for tissue engineering
applications, there is a critical number of cells required
for scaffolds to appear bioactive. There must be a large
enough area available for cells to bind to in order to support
a large enough population of cells within the scaffold; the
existence of a critical density of cells has been hypothesized
as a result of a number of experiments studying cell
scaffold interactions (1).
The development of a highly detailed model, describing
the number of receptors utilized per bound cell and the
nature of the binding and receptor sites, is required to
describe even a simple interaction between a cell and a
generic scaffold surface. However, a more generic explanation can be used to indicate both the complexity of the cell
scaffold interaction and the significant influence the scaffold pore structure has on scaffold bioactivity. In particular, we will examine the affect of another critical factor on
scaffold bioactivity: mean scaffold pore size.
The structure of a porous scaffold is defined by the pore
volume fraction, mean pore size, and pore orientation in
the scaffold. All of these characteristics have been shown to
significantly affect the bioactivity of the scaffold. The pore
volume fraction and the mean pore size together define the
specific surface area of the scaffold, the total surface area of
pore walls available for cellular binding. Increasing the
mean pore size while keeping the pore volume fraction
constant decreases the specific surface area of a scaffold.
Decreasing the pore volume fraction and keeping the mean
pore size constant increases the specific surface area (140).
It has been estimated that a 30-fold increase in pore
diameter leads to a 27-fold decrease in specific surface
(2). A change in the specific surface area of the scaffold
significantly changes the area available for cells to bind to.
More specifically, the surface density of bound cells (F) in a
3D dimensional porous scaffold is a function of both the
density of bound cells in the scaffold (r) and the specific
surface of the scaffold (s):
F
r
s
187
the cell, 1050 mm for most cell types. When the scaffold
pore size is smaller than this critical dimension, cells will
be unable to migrate through the porous structure, and will
be unable to infiltrate and bind to the template. These
upper and lower bounds of the scaffold pore diameter,
mediated by cell size and specific surface requirements,
have been determined experimentally for each cell type for
tissues where regenerative templates have been used
(3,141); however, future work is necessary to develop a
better understanding of cell adhesion and its relation of
scaffold structure.
The shape of the pores that make up the porous scaffold
must also be considered; slight changes in the mean shape
of the pores can result in significant variations in the
mechanical properties of the scaffold (140). In addition,
changes in mean pore shape may also play a role in defining
the areas of the scaffold available or unavailable for binding and in defining available directions for cell migration.
The template pore structure plays a very significant role in
defining the overall bioactivity of the scaffold and the openor closed-cell nature, the mean pore size, relative density,
and pore shape and orientation all are critical components
to consider.
TISSUE ENGINEERING OF THE SKIN
Structure and Function of Skin
Mammalian skin is a stratified tissue made up of three
distinct layers of tissue: the epidermis, the basement
membrane, and the dermis. Each tissue displays unique
structural and functional properties as well as distinctive
responses to injury or damage. These tissues, an epithelial
layer (epidermis in skin), a basement membrane layer, and
a stromal layer (dermis in skin) make up the previously
described tissue triad for the skin (1,8,142). Using the
tissue triad to model a generic tissue, the epithelia covers
all body surfaces, tubes, and cavities, and is separated from
the underlying stroma by a continuous basement membrane layer. As the basement membrane is totally acellular
and is not penetrated by the vascular system, the survival
of the epithelia depends on diffusion of metabolites, nutrients, oxygen, and waste products across the basement
membrane to and from the stroma. The stromal layer
contains the vascular system and other supporting tissues
(connective tissues) that serve to nourish and anchor the
basement membrane and the epithelia. In addition, while
both the stromal and the basement membrane layers contain an extracellular matrix structure, the epithelial layer
does not. In the following sections, the structure and
function as well as the response to injury of each of the
layers of the tissue triad that constitutes adult skin will be
described in detail.
Morphology and Function of the Epidermis
The epidermis is the exterior layer of tissue that makes up
the skin. The epidermal layers act as a physical barrier to
protect the organism against microorganisms; prevents
organismic dehydration; and protects the organism from
mechanical, thermal, chemical, and UV insults. It is a
188
189
190
191
192
193
chemical composition, template residence time, and template pore structure needed to create a bioactive scaffold
that prevented contraction and induced regeneration
(1,3,134).
The ECM analogs that were used successfully to induce
skin regeneration are graft copolymers of type I collagen
and chondroitin-6-sulfate, a GAG, with a collagen:GAG
weight ratio of 98:2 (3). The porous structure of the DRT
was produced using a freezedrying process. The collagen
GAG (CG) copolymer was produced in slurry form from
microfibrillar collagen, an aqueous glycosaminoglycan
solution, and acetic acid. The slurry was frozen to a final
temperature of 40 8C and then sublimated [pressure
<100 mtorr (13.3 Pa), temperature = 0 8C]; after freezing,
an interpenetrating network of ice crystals that is surrounded by collagen and GAG fibers has formed. The
sublimation process converts all of the ice crystals formed
in the frozen slurry into vapor and generates empty pores,
creating a collagenGAG scaffold formed from interconnected sublimated pores (3,165). The scaffold structure
(pore size, specific surface) can be adjusted by varying
the temperature of freezing of the CG slurry prior to
sublimation; a lower temperature of freezing increases
the frequency of nucleation of ice crystals in the slurry
and decreases the rate of material transport within the
slurry. These two processes result in the formation of
smaller ice crystals, and therefore smaller pores after
sublimation, for lower temperatures of freezing
(3,166,167). In addition to being able to adjust the composition and the pore structure, the template residence time
can be adjusted by changing the cross-link density, allowing the fabrication of scaffolds with specific degradation
rates (3,105). Both chemically (i.e., glutaraldehyde or carbodiimide based cross-linking) and physically induced (i.e.,
dehydrothermal crosslinking) covalent bonds between collagen fibers (cross-links) can be introduced; as the scaffold
becomes more highly cross-linked, it is increasingly difficult to degrade through enzymatic digestion. Adjustment
of the severity of cross-linking (increasing the chemical
exposure time or increasing the heat and/or exposure time
to a dehydrating environment increases the severity of
cross-linking) allows for adjustment of the scaffold crosslink density and therefore degradation rate (3,120). Previous research has determined that crosslinked collagen
scaffolds degrade at a rate that monotonically decreases
with increasing crosslink density (105). Systematic use of
the contraction inhibition criterion was used to select the
average pore diameter and biodegradation rate of the DRT
that results in an optimal regeneration result. The speed of
contraction of a wound site was measured using the wound
half-life criterion, the time it took for the wound to decrease
in area by 50% from its original size.
The kinetics of contraction of full-thickness skin wounds
in the guinea pig were used to separate CG copolymer
grafts into three classes: Class 0, I, or II (Fig. 2). The guinea
pig model was employed during early studies because of the
vigorous contraction observed in skin wounds; this rapid
and significant contraction was used to identify templates
that were active in preventing contraction and inducing
regeneration (108). While the skin of most mammals is
securely tethered to the underlying fascia and skin wounds
194
both class I and class II healing devices are useful clinically. The scaffold that led to these two healing modes was
identified as having maximal biological activity, termed
the DRT.
A homologous series of ECM analogs, varying in
scaffold pore diameter from 10 to 1000 mm, was used
in the above studies to determine the optimal pore diameter necessary to prevent class 0 contraction (Fig. 4).
Maximum delay of wound contraction half-life, up to 27 3
days, was observed when the average pore diameter was in
Figure 4. Identification of the optimal pore diameter for a bioactive extracellular matrix analog designed to induce skin regeneration. The range of maximal contraction-delaying activity for
collagenGAG scaffolds was observed when the average pore diameter of the scaffold was between 20 and 120 mm. The limits to the
area of maximal activity are indicated by broken lines and correspond to the range where contraction was most delayed (13).
195
196
197
198
199
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57. Urban RM, Jacobs JJ, Tomlinson MJ, Gavrilovic J, Black
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62. Slack JMW. Stem cells in epithelial tissues. Science 2000;
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in vivo degradability and of immunogenicity of collagen by
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in vivo collagen degradation rate with in vitro measurements. J Biomed Mater Res 1975;6:623625.
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pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials In press, 2004.
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1987;17:431438.
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MT, Bondoc CC, Quinby WC, Jr., Behringer GE, Ackroyd
FW. Increased survival after massive thermal injuries in
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Surg 1994;17:9193.
174. Besner GE, Klamar JE. Integra Artificial Skin as a useful
adjunct in the treatment of purpura fulminans. J Burn Care
Rehab 1998;19:324329.
175. Spence RJ. The use of Integra for contracture release. Burn
Care Rehabil. 1998;19:S173.
176. Lorenz C, Petracic A, Hohl H-P, Wessel L, Waag K-L. Early
wound closure and early reconstruction: Experience with a
dermal substitute in a child with 60 percent surface area
burn. Burns 1997;23:505508.
177. Pandya AN, Woodward B, Parkhouse N. The use of cultured
autologous keratinocytes with Integra in the resurfacing of
acute burns. Plast Reconstr Surg 1998;102:825828.
178. Lattari V, Jones LM, Varcelotti JR, Latenser BA, Sherman
HF, Barrette RR. The use of permanent dermal allograft in
full-thickness burns of the hand and foot: a report of three
cases. J Burn Care Rehabil 1997;18:147155.
179. Tsai CC, Lin SD, Lai CS, Lin TM. The use of composite
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major burn patientsone year follow-up. Kaohsiung J
Med Sci 1999;15:651658.
See also ENGINEERED
SKIN, BIOMECHANICS OF
YAN CHEN
BRIAN L. DAVIS
Department of Biomedical
Engineering/ND20 Lerner
Research Institute
The Cleveland Clinic
Foundation
Cleveland, Ohio
INTRODUCTION
Skin, the bodys largest organ, accounts for about 16% of an
average adults body weight and occupies a surface area of
SKIN, BIOMECHANICS OF
Epidermal/dermal
interface
500 m
203
Figure 1. Layers of skin (left) and view of rete ridges (right) (1).
Microstructure of Skin
The mechanical properties of skin have long interested
dermatologists and bioengineers (211). Studies of the
mechanical properties of skin could provide objective information related to skin and the changes it undergoes with
age and disease. For instance, knowledge of the skins
mechanical properties is of potential use in assessing conditions of connective tissue disease, skin aging, wound
healing, and scarring.
Like any other material, the mechanical properties of
skin are determined by those of its structural constituents.
Major structural components of skin are elastin fibers,
collagen fibers, and the ground substance. The individual
mechanical and structural properties of collagen fibers,
elastin fibers, and their interaction with the ground substances in skin form the basis of mechanical properties of
skin.
Collagen. Collagen, the bodys most abundant and
common protein, represents approximately 72% of the
dry weight of dermal tissue. There are now more than
19 known collagen types, each of which is a genetically
distinct product. The collagen of adult dermis is mainly
type I (8590%), with 811% of type III and 24% of type V
collagen. In all connective tissues, collagen exists as fibers
made up of crimped fibrils. Depending on the tissue, a
collagen fibril varies from 50 nm to 300 nm in diameter.
Collagen fibers in skin are randomly oriented in layers or
lamellae, which give skin large extensibility and resiliency
under stress. This arrangement contrasts with that found
in the tendon and ligament, where the parallel alignment
of collagen fibers gives these tissues higher values of tensile
strength requirement.
Collagen fibrils are stabilized and strengthened by the
formation of covalent cross-links. These cross-links are
formed by lysine and hydroxylysine residues. The intermolecular cross-links are formed by the joining of two
hydroxylysine residues and one lysine residue. The
cross-links are formed between residues near the amino
terminus of one collagen molecule and the carboxyl terminus of another.
There is evidence that in the presence of hyperglycemia
(such as in diabetes), some proteins, such as collagen,
undergo nonenzymatic glycation (1215). This process
modifies the structure of collagen and has a direct effect
on the mechanical properties of collagen, resulting in
increased mechanical stiffness and decreased flexibility
204
SKIN, BIOMECHANICS OF
SKIN, BIOMECHANICS OF
and non-time-dependent values (e.g., elasticity). The measurement of mechanical properties of skin can be performed either in vitro or in vivo. Results from in vitro
tests are estimates of properties that are assumed to have
an important influence on function in vivo and can provide
information about the basic mechanical properties of
strength, elasticity, or density inherent in the architecture
of skin. However, in vitro studies are limited in that the
characteristics of isolated skin are modified. Dissected skin
samples no longer have the same physiological properties
as in vivo skin, such as those of internal tension, hydration,
and vascularization. In vivo tests may provide information
on the function and the kinetics of change in mechanical
properties.
Stress (MPa)
0.4
205
0.8
Strain
Figure 2. Typical stress-strain curve of skin under incremental
loading (4).
mid-strain region, the curve increases in a roughly exponential manner (b) until, at the high-strain region, it
becomes almost a straight line (c) immediately before
rupture occurs. The accepted explanation of the curve is
that the initial deformation (Fig. 2a) is due to deformation
of the delicate elastin network; the second part of the curve
(b) is due to a gradual straightening of the randomly
oriented collagen fibers; the third part of the curve (c) is
because most collagen fibers are elongated in the direction
of the stress. If the initial part of this curve is magnified, a
straight-line approximation will allow the calculation of
elastic properties such as Youngs modulus. From a functional part of view, the first parts of the curve are more
important because they correspond to the physiological
range in which the skin normally functions.
Anisotropy. Like most composite materials, skin is
anisotropic. This mechanical behavior of human skin can
be demonstrated by stretching skin in different directions
or by a biaxial loading test (26). Results from tests such as
these show directional variance related to lines of tension
or cleavage (known as Langers lines) within the skin that
are characteristic for each part of the body. They are named
after Austro-Hungarian anatomist Karl Langer (1819
1887), the first to systematically investigate the configuration of the tension on cuts in the human body. Microscopic
examination of sections of skin along and across Langers
lines shows a preferential orientation of the collagen fibers
of skin. The orientation seems to be at an angle slightly less
than 458 from the direction of the lines. Ridge and Wright
(27) performed a series of experiments with an extensometer in which they stretched pieces of skin with and
against the normal skin tension lines. They could show a
clear difference in the directional mechanical properties in
the skin, which corresponded to Langers lines.
Measurement of Skin Mechanical Properties
Information about the mechanical properties of skin falls
under three broad categories: strength values (e.g., breaking strain), time-dependent values (e.g., creep, relaxation),
206
SKIN, BIOMECHANICS OF
SKIN, BIOMECHANICS OF
M ean
force
(N /m m )
207
6
4
2
0
SUMMARY
Skin has multiple essential functions ranging from protection against injury or invasion by microorganisms, to a
barrier to water loss, to maintaining normal body temperature. It consists primarily of two principal layers
epidermis and dermisand various sublayers. From a
mechanical point of view, these layers have stiffness values
that can differ by three orders of magnitude! The area of
skin that withstands the greatest daily history of loading
that under the foothas an interface between the dermis
and the epidermis characterized by rete ridges. The
precise mechanical function of these ridges is not yet clear.
What is known is that this interface is profoundly affected
by the magnitudes of shear and pressure loading that
plantar soft tissue is required to withstand. Areas that
have higher loading (e.g., heel or metatarsal head region)
have a dermis that is more tightly bonded to the subcutaneous soft tissue than other regions. In this respect, skin
seems to follow the form follows function law (or Wolffs
Law) that is usually used to describe bones adaptation to
applied loading. When these loads become extreme (e.g.,
greater than 1 MPa applied pressure), even the short
weight-bearing intervals during gait are sufficient to lead
to skin breakdown. The precise site for the initiation of
failure (e.g., which layer of skin fails first) has yet to be
determined. As skin breakdown under the foot is a clinical
problem with significant risks for the patient, it is likely
that research into this problem will continue until skin
failure mechanisms are better understood. These may
then serve as the basis for better prevention or treatment
strategies.
208
SLEEP LABORATORY
BIBLIOGRAPHY
1. Chen Y. The influence of diabetes on mechanical properties
of skin. Unpublished doctoral dissertation. Cleveland, OH:
Cleveland State University; April 2003.
2. Ridge MD, Wright V. The description of skin stiffness. J
Biorheol 1964;10:139155.
3. Daly CH. The biomechanical characteristics of human skin.
Ph.D. Thesis, University of Strathcylde, Glasgow, Scotland,
1966.
4. Daly CH. Biomechanical properties of dermis. J Invest
Dermatol 1982;79(Suppl 1):17s20s.
5. Danielson DA. Human skin as an elastic membrane. J
Biomech 1973;6:539546.
6. Lanir Y, Fung YC. Two-dimensional mechanical properties
of rabbit skin. II. Experimental Results. J Biomech 1974;7:
171182.
7. Lanir Y. Structural theory for the homogeneous biaxial
stress-strain relationships in flat collagenous tissues. J Biomech 1979;12:423.
8. Warren R, Gartstein V, Kligman AM, Montagna W, Allendorf
RA, Ridder GM. Age, sunlight, and facial skin: A histologic
and quantitative study. J Am Acad Dermatol 1991;25:751
760.
9. Reihsner R, Balogh B, Menzel EJ. Two-dimensional elastic
properties of human skin in terms of an incremental model
at the in vivo configuration. Med Eng Phys 1995;17:304313.
10. Potts RO, Buras EM Jr, Chrisman DA Jr. Changes with age
in the moisture content of human skin. J Invest Dermatol
1984;82:97100.
11. Diridollou S, Berson M, Vabre V, Black D, Karlsson B, Auriol
F, Gregoire JM, Yvon C, Vaillant L, Gall Y, Patat F. An in vivo
method for measuring the mechanical properties of the skin
using ultrasound. Ultrasound Med Biol 1998;24:215224.
12. Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann
Intern Med 1984;101(4):527537.
13. Buckingham B, Reiser KM. Relationship between the content
of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in Type
I diabetes mellitus. J Clin Invest 1990;86:10461054.
14. Delbridge L, Ellis CS, Lequesne LP. Non-enzymatic glycosylation of keratin from the diabetic foot. Br J Surg 1983;70:
305.
15. Monnier VM, Kohn RR, Cerami A. Accelerated age-related
browning of human collagen in diabetes mellitus. Proc Natl
Acad Sci USA 1984;81:583587.
16. Cerami A, Vlassara H, Brownlee M. Role of advanced glycosylation products in complications of diabetes. Diabetes Care
1988;11(Suppl 1):7379.
17. Hamlin CR, Kohn RR, Luschin JJ. Apparent accelerated
aging of human collagen in diabetes mellitus. Diabetes
1975;24:902904.
18. Reiser KM. Nonenzymatic glycation of collagen in aging and
diabetes. Proc Soc Exp Biol Med 1991;196:1729.
19. Kennedy L, Baynes JW. Non-enzymatic glycosylation and the
chronic complications of diabetes: An overview. Diabetologia
1984;26:9398.
20. Makita Z, Radoff S, Rayfield EJ, Yang Z, Skolnik E, Delaney
V, Friedman EA, Cerami A, Vlassara H. Advanced glycosylation end products in patients with diabetic nephropathy. N
Engl J Med 1991;325(12):836842.
21. Elkeles RS, Wolfe JHN. ABC of vascular diseases. The diabetic foot. BMJ 1991;303:10531055.
22. Dick JC. The tension and resistance to stretching of human
skin and other membranes. J Physiol 1951;112:102113.
23. King AL, Lawton RW. Elasticity of body tissues. In: Glasser
O, editor. Medical Physics, Vol. 3. Chicago: Yearbook Publishers; 1960. 234247.
24. Daly CH. The role of elastin in the mechanical behavior of
human skin. Proc. 8th Intl. Conf. Med. Biol. Engr.. Chicago,
IL: 1969: 1827.
25. Minns RJ, Soden PD, Jackson DS. The role of the fibrous
components and the ground substance in the mechanical
properties of biologic tissues: A preliminary investigation.
J Biomech 1973;6 153165.
26. Tong P, Fung YC. The stress-strain relationships for the skin.
J Biomech 1976;9:649657.
27. Ridge MD, Wright V. The directional effects of skin. A bioengineering study of skin with particular reference to Langers lines. J Invest Dermatol 1966;64:341346.
28. Yamada H. Strength of Biological Materials. Baltimore, MD:
Williams & Wilkins; 1970.
29. Lanir Y, Fung YC. Two-dimensional mechanical properties
of rabbit skin. I. Experimental System. J Biomech 1974;7
2934.
30. Laing P. The development and complications of diabetic foot
ulcers. Am J Surg 1998;176(Suppl 2A):11S19S.
31. Brand PW. Pathomechanics of diabetic (neurotrophic) ulcer
and its conservative management. In: Bergan JJ, Yao JST,
editors. Gangrene and Severe Ischaemia of the Lower Extremities. New York: Grune & Stratton; 1978. p 185189.
32. Davis BL. Foot ulceration: Hypotheses concerning shear and
vertical forces acting on adjacent regions of skin. Med Hypoth
1993;40:4447.
33. Thompson DL. Finite element modeling of the diabetic foot.
Unpublished Masters Dissertation, Ohio State University,
1998.
See also SKIN
SLEEP LABORATORY
RICHARD K. BOGAN
SHAWN D. YOUNGSTEDT
University of South Carolina
Columbia, South Carolina
INTRODUCTION
Sleep is a fundamental, homeostatic process necessary for
human existence and quality of life. Sleep disorders
account for impairment of alertness (1); cognitive function
(2), especially short-term memory and divided-attention
tasks (3); mood (4); work productivity (5); and driving
ability (and hence, an increase in automobile accidents).
Obstructive sleep apnea has been clearly linked to cardiovascular disease.
There are > 80 sleep disorders, which generally increase in
prevalence with age. Indeed, > 50% of adults over age 60 years
suffer from some sleep-related complaint (6), including daytime fatigue, difficulty initiating or maintaining sleep, snoring, obstructive apnea, insomnia, restless legs syndrome,
narcolepsy, or circadian rhythm disorders. Most disorders
have attendant morbidity issues. For example, patients with
sleep apnea have an increased risk of cardiovascular disease,
stroke, and diabetes. Patients with protracted insomnia have
SLEEP LABORATORY
Side
Table
Side
Table
4' x 6'
Entry
Door
Door
Side
Table
Side
Table
Full or Queen
Size Bed
Full or Queen
Size Bed
Private
Patient
Sleep Room
209
13' x 12'
TV
Cabinet
9' x 6'
Patient 3/4
Bath
Private
Patient
Sleep Room
TV
Cabinet
Clean Linen
Shelving
Patient 3/4
Bath
Door
w/Loevers
Door
4' Corridor
Open Technologist Counter
w/ Hollow Columns for Cabling
Attending Tech
Technologist
Bath
Clinical
Cleaning
Copier
Fax Area
Dirty
Storage
Clinical Supply
Storage
Inductance plethysmography
Intercostal EMG
Esophageal pressure
Esophageal pH
Pulse oximetry
Transcutaneous oximetry
Transcutaneous CO2
Electrocardiogram
Blood pressure
Penile tumescence
Body position
210
SLEEP LABORATORY
Electromyography
Three electromyographic (EMG) electrodes placed in the
mentalissubmentalis area allow detection of EMG activity. During sleep, there is a gradual decline in EMG
activity, and the dramatic reduction of muscle tone during
REM, makes the EMG an important confirmation of REM
sleep. Again, adequate removal of oils and dead skin cells
with a conductive electrode placement enhances signal
processing.
Electrodes or strain gauge sensors are also commonly
placed on the tibialis muscles (Fig. 3). The EMG and
movement signals from the lower extremities, and sometimes the arms, allow measures of isolated movements, as
well as periodic limb movements that may be seen in
restless legs syndrome, periodic limb movements of sleep,
REM behavior disorder, seizures, parasomnias, and other
disorders.
Electrooculography
The electrooculogram (EOG) is a measurement of eye
activity. Phasic bursts of rapid eye movement occur during
rapid eye movement sleep (REM sleep). The EOG is important for recognition of REM sleep, as well as for detecting
the transition from wakefulness to Stage 1 sleep, which is
characterized by slow, rolling eye movements.
The EOG recordings are possible due to a small electropotential difference from the cornea to the retina. The electrodes are positioned at the right outer canthus (ROC) and
the left outer canthus (LOC), eferenced to auricular electrodes. Thus, ROC/A1 and LOC/A2 will register as out-of-phase
pen deflections. This facilitates artifact recognition, as well as
EEG activity recorded in the eye electrodes. EOG placements
incorporate a somewhat superior placement of the electrode
on one eye and inferior on the other eye, which allows
recognition of vertical eye movements.
SLEEP LABORATORY
211
212
SLEEP LABORATORY
Daytime Sleepiness
Objective assessment of daytime sleepiness is another
important laboratory diagnostic measure. The multiple
sleep latency test involves a series of nap opportunities
at 2 h intervals during the day. The standardized technique
and normative data facilitate objective measures of excessive daytime sleepiness. This test is primarily used in the
diagnosis of narcolepsy. The maintenance of wakefulness
test is similar to the multiple sleep latency test, but
requires the individual to attempt to remain awake during
20 or 40 min nap opportunities in a dark room.
Treatment Guidelines. Practice-based guidelines by the
American Academy of Sleep Medicine and medical specialty societies have established guidelines for diagnosing
and treating sleep disorders. These can be accessed on their
website (www.aasmnet.org).
ADDITIONAL AMBULATORY MEASURES
Alternative or ancillary devices have been developed, primarily in the area of sleep-disordered breathing and brain
state (sleepwake estimate). Screening devices have been
developed for obstructive sleep apnea primarily. Portable
outpatient systems for unsupervised polysomnography are
available. The unattended study is considered a level II
evaluation. Level III is portable sleep apnea testing, monitoring airflow, effort, electrocardiogram, and oxygen saturation.
Level IV is arterial oxygen saturation measurement alone.
Actigraphy incorporates an accelerometer used to measure wrist movement. Complex algorithms have been
developed to estimate sleep/wake state, periodic limb
movements, and circadian rhythm abnormalities. Actigraphy is particularly useful for long-term monitoring of
patients in their homes, and for detection of daytime napping, which is usually not possible for EEG, as it is
restricted to the night.
DIGITAL PGS AND FUTURE TRENDS
The EEG, EOG, and EMG signals were traditionally
recorded in a sleep laboratory with limited channels on
213
Further Reading
Bassetti CL. Sleep and stroke. Semin Neurol 2005;25:1932.
Drummond SP, Gillin JC, Smith TL, DeModena A. The sleep
of abstinent and pure primary alcoholic patients: Natural
course and relationship to relapse. Alcohol Clin Exp Res
1998;22:17961802.
George CF. Sleep. 5: Driving and automobile crashes in patients
with obstructive sleep apnoea/hypopnoea syndrome. Thorax
2004;59:804807.
Phillips B. Sleep disordered breathing and cardiovascular disease.
Sleep Med Rev 2005;9:131140.
Spira AP, Friedman L, Flint A, Sheikh JI. Interaction of sleep
disturbances and anxiety in later life: Perspectives and recommendations for future research. J Geriatr Psychiatry Neurol
2005;18:109115.
Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev 2005;9:211
224.
See also CONTINUOUS
GRAPHY;
SLEEP
STUDIES,
COMPUTER
ANALYSIS
OF;
VENTILATORY
MONITORING.
INTRODUCTION
BIBLIOGRAPHY
1. Schnieder C, Fulda S, Schulz H. Daytime variation in performances and tiredness/sleepiness ratings in patients with
insomnia, narcoplepsy, sleep apnea and normal controls.
J Sleep Res 2004;13:373383.
2. Ancoli-Israel S, Cooke JR. Prevalence and comorbidity of
insomnia and effect on functioning in elderly populations.
J Am Geriatr Soc 2005;53(Suppl. 7):S264S271.
3. Thomas RJ, et al. Functional imaging of working memory in
obstructive sleep-disordered breathing. J Appl Phyiol 2005;
98:22262234.
4. Drake CL, Roehrs T, Roth T. Insomnia causes, consequences,
and therapeutics: An overview. Depress Anxiety 2003;18:163
176.
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215
Figure 1. Illustration of Stage 1 sleep in Patient C. Epoch width and recording channels are the
same as those in Fig. 1. Note the slowed eye movements (arrow).
further divided into four stages, according to rules established by Rechtschaffen and Kales (R&K) (10). The
following outlines these stages and summarizes the major
criteria that characterize them. Stage 1 Sleep, illustrated
in Fig. 1, consists of a relatively low voltage EEG, with
activity prominently from 2 to 7 cycles per second (Hz).
Waves at this frequency are referred to as theta waves (12).
Rapid eye movements are not present and eye movements
are generally slow and rolling. This stage typically occurs
during the transition from wakefulness (seen in Fig. 2) to
the other sleep stages, and is relatively short. Stage 2
Sleep, illustrated in Fig. 3, is marked by K complexes
and sleep spindles on a background of relatively low voltage EEG. The K complexes are negative, sharp, high
voltage waves that are usually followed by a positive
component. The complex duration, according to the R&K
rules, should not exceed 0.5 s. The K complexes can occur
spontaneously or in response to sudden stimuli and they
are highest in amplitude over the vertex scalp regions
(10,11). Sleep spindles are defined as bursts of waves
having a frequency of 12 to 15 [Hz] (11, p. 16). In addition
to the K complexes and sleep spindles, Stage 2 sleep lacks
waves of high amplitude and slow activity seen in later
stages (10). Stage 3 Sleep, illustrated in Fig. 4, is defined by
delta waves, or slow waves of 2 Hz or less and amplitudes
>75 mV (11,12). The EEG activity in Stage 3 should account
for 2050% of the time interval (epoch) studied (10). Sleep
spindles may or may not be present. Stage 4 Sleep,
illustrated in Fig. 5, is defined when >50% of the
epoch consists of high amplitude waves that are 2 Hz or
slower.
216
Figure 2. Example of a 30 s epoch of wakefulness from patient C being evaluated for a sleep
disorder. The labels on the left indicate the measures at each channel of recording. The first two
channels are EEG from the left central and left occipital scalp sites. LOC and ROC left and right
eye movements followed by chin EMG, nasal/oral air flow, thorax and abdominal respiratory effort,
oxygen saturation, electrocardiogram, average pulse, left and right leg movement. Labels on the
right indicate the patients body position, average oxygen saturation (not shown), average pulse
rate, level of continuous positive or bilevel air pressure (CPAP/BIPAP), if administered.
Figure 3. Illustration of Stage 2 sleep in patient C. Epoch width and recording channels are the
same as those in Fig. 2. Note the K complexes (arrow Channel 1) and sleep spindles (arrow Channel 2).
Figure 4. Illustration of Stage 3 sleep in patient C. Epoch width and recording channels are the
same as those in Fig. 2. Note the high amplitude slow EEG waves and the sleep spindles in EEG
channels 1 and 2 (arrow).
Figure 5. Illustration of Stage 4 sleep in patient C. Epoch width and recording channels are the
same as in Fig. 2. Note the high amplitude slow EEG waves in EEG channels 1 and 2 (arrow). This
slow activity occupies >50% of the epoch.
217
218
Figure 6. Illustration of Stage REM sleep in patient G. Epoch window and recording channels are
the same as in Fig. 2. Note the low voltage EEG in EEG channels 1 and 2, the rapid eye movements in
eye channels 3 and 4 (arrow), and the low amplitude chin EMG in channel 5.
stages before it is inspected manually by a polysomnographer. Since this method is not fully computer automated,
but is computer assisted, the investigators referred to this
approach as computer-assisted sleep staging (CASS).
Because sleep stages are not distinct entities, computer
errors are made. Empirical studies confirm that, despite
our best effort to demarcate sleep stages for computer
detection, errors occur, especially for the less clearly
defined stages (13). For example, Agarwal and Gotman
(13) reported that many errors occur when attempting to
define Stage 1 sleep, perhaps the most ambiguous, which
was often misclassified as either wakefulness or Stage 2
sleep. For computers to identify components of sleep, these
components must be clearly defined. At present, the best
defined features of sleep are the various stages according to
the R&K rules. Some of these rules are specific enough for
an algorithm to be programmed so that a computer can
identify it on a polysomnogram. For example, Stage 3 sleep
is defined by delta waves with amplitudes >75 mV, present
between 20 and 50% of the time. Other definitions are less
precise, such as the definition of Stage 2 sleep, which is
marked by sleep spindles, K-complexes, and waves that
lack the amplitude and slower activity seen in sleep Stages
3 and 4. Stage 2 sleep is more difficult to quantify and,
therefore, less amenable to detection by computers.
Computer Analysis of Sleep Microstructure
From a more academic, less clinical, perspective, computers have been used to assist with analysis of the microstructure of sleep, such as parsing out the various
components of specific waves (e.g., sleep spindles, K complexes) and exploring their relationships to various sleep
problems. Although the presence of sleep spindles in Stage
2 sleep is well known, the different types of spindles and
their subsequent spatial distribution are less well studied.
With the aid of computers, two types of spindles have been
identified: 12 spindles per second located primarily in the
frontal region and 14 spindles per second located primarily
in the centroparietal region (14). Our understanding of K
complexes has also been improved with the aid of computers. Specifically, a classification of K complexes has been
recommended, that includes K0 complexes (without sleep
spindles), K1 complexes (spindles preceding the K complexes), K2 complexes (spindles occurring simultaneously
with the K complexes), and K3 complexes (spindles following the K complexes (14)).
Computers have also been used to assess new components within the stages of sleep (e.g., slow wave sleep and
REM sleep). Initially, slow wave sleep was defined as sleep
marked by delta waves, occurring during stages 3 and 4.
Delta waves were believed to be uniform, with no variable
components. However, with the aid of computers, two types
of these waves have been identified with scalp topographical differences. Sinusoidal 12 s1 delta waves tend to be
located frontally, and have been compared to K complexes
that are not precipitated by sensory stimuli. Polymorphic
<1 s1 delta waves, on the other hand, are located parietotemporally. The role of these components is presently
unclear. Our understanding of the microelements of REM
sleep is also being explored. For instance, although saw-
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220
Figure 7. Illustration of obstructive sleep apnea in patient M. Epoch window is 120 s. Recording
channels are the same as in Fig. 16. Arrow indicates EEG arousal following the event.
221
Figure 8. Illustration of computer summary of nocturnal polysomnogram for patient M. Note the
oxygen desaturations (SaO2) associated with respiratory events (Respiratory Module). Periodic limb
movements (PLM Module) were not present.
222
Computer analysis is also often dependent on measurement of the wakefulness alpha activity, which causes
problems with low alpha subjects. In this case, it is an
advantage to rely on theta activity and non-EEG waveforms (21,22). Also, the distinction between REM and
NREM sleep is difficult in patients with poor sigma spindles or if the spindles are of a frequency outside the usual
range (18). Toussaint et al. (23) discussed the first-night
effect in sleep studies, noted by lower sleep efficiency,
increased wakefulness, and longer REM periods in
patients. Computer algorithms have been difficult to derive
that can take into account the first-night effect in individuals because it is relative to the persons normal sleep
rather than referring to objective, specific changes in sleep
across all individuals.
Interindividual differences in sleep measures have also
been demonstrated. For example, variability in polysomnograms has been associated with both gender (2426) and
223
CONCLUSIONS
Advances in technology have contributed to major insights
into the mechanisms and processes of sleep. However,
computer programs can be written to recognize only what
we understand and can clearly define (14). At present,
reliable completely automated sleep scoring systems are
not available. The EEG variables present particular difficulties for automated sleep staging systems. However, the
ability of computers to store large amounts of data, to
organize and consolidate these data, and to perform summary statistics has allowed the polysomnogram to become
a significant clinical and research tool. It provides
clinicians and scientists with increased power for the
224
BIBLIOGRAPHY
1. McNish R. The Philosophy of Sleep, 1st ed. New York: D.
Appelton & Company; 1934.
2. Kleitman N. Sleep and Wakefulness. Chicago: The University
of Chicago Press; 1939.
3. Aserinsky E, Kleitman N. Regularly occurring periods of eye
motility, and concomitant phenomena, during sleep. Science
1953;118:273274.
4. Aserinsky E, Kleitman N. Two types of ocular motility occurring in sleep. J Appl Physiol, 1955;8:1118.
5. Dement W, Kleitman N. Cyclic variations in EEG during sleep
and their relation to eye movements, body motility, and dreaming. Electroencephalogr Clin Neurophysiol 1957;9:673690.
6. Hobson JA. Sleep. New York: Scientific American Library;
1989.
7. Dement WC. Normal sleep and its variations. In: Kryger MH,
Roth T, Dement WC, editors. Principles and Practice of
Sleep Medicine, 2nd ed. Philadelphia: W.B. Saunders; 1994;
p 315.
8. American Electroencephalographic Society. Guideline fifteen:
Guidelines for polygraphic assessment of sleep-related disorders (polysomnography). J Clin Neurophysiol 1994;11:116
124.
9. Bartolo A, Clymer BD, Golish JA, Burgess RC. The polysomnogram assay: a method to represent the overnight polysomnogram in a condensed format. Comput Biomed Res 2000;
33:110125.
10. Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of
human subjects. University of California: Brain Information
Service; 1968.
11. Siegel J. The neural control of sleep and waking. New York:
Springer-Verlag; 2002.
12. Hauri PJ. The Sleep Disorders. Kalamazoo (MI): The Upjohn
Company; 1982.
13. Agarwal R, Gotman J. Computer-assisted sleep staging.
IEEE Transactions on biomedical engineering 2001;48:
14121423.
14. Kubicki S, Herrmann WM. The future of computer-assisted
investigation of the polysomnogram: Sleep microstructure.
J Clini Neurophysiol 1996;13:285294.
15. Agarwal R, Gotman J. Digital tools in polysomnography.
J. Clin Neurophysiol, 2002;19(2):136143.
16. Moser NJ, Phillips B, Berry DT, Harbison L. What is hypopnea anyway? Chest 1994;105(2):426428.
17. Broughton RJ, Hasan J. Quantitative topographic electroencephalic mapping during drowsiness and sleep onset.
J Clin Neurophysiol 1995;12:372386.
18. Jankel WR, Niedermeyer E. Sleep spindles. J Clin Neurophysilo 1985;2:135.
19. Martens WLJ, Declerck AC, Kums DJThM, Wauquier A.
Considerations on a computerized analysis of long-term polygraphic recordings. In: Stefan H, Burr W, editors. EEG
monitoring. Stuttgart: Gustav Fisher; 1982; p 265-274.
20. Badia P, Wright KP, Wauquier A. Fluctuations in SingleHerz EEG activity during the transition to sleep. In: Ogilvie
RD, Harsh JR, editors. Sleep Onset: Normal and Abnormal
Processes. Washington (DC): American Psychological Association; 1995. p 201218.
21. Hasan J. Differentiation of normal and disturbed sleep by
automatic analysis. Acta Phys Scand(Suppl) 1983;526:1103.
22. Hasan J, Hirvonen K, Va rri A, Ha kkinen V, Loula P. Validation of computer analysed polygraphic patterns during drowsiness and sleep onset. Electroencephalogr Clin Neurophyso
1993;87:117127.
23. Toussaint M, et al. Changes in EEG power density during
sleep laboratory adaptation. Sleep 1997;20(12):12011207.
24. Carrier J, et al. The effects of age and gender of sleep EEG
power spectral density in the middle years of life (ages 2060
years old). Psychophysiology 2001;38:232242.
25. Ehlers CL. Kupfer DJ. Slow-wave sleep: Do young adult men
and women age differently? J Sleep Res 1997;6(3):211215.
26. Huupponen E, et al. A study on gender and age differences in
sleep spindles. Neuropsychobiology 2002;45(2):99105.
27. Hirshkowitz M, Moore CA. Issues in computerized polysomnography. Sleep 1994;17(2):105112.
28. Tan X, Campbell IG, Feinberg I. Internight reliability and
benchmark values for computer analyses of non-rapid eye
movement (NREM) and REM EEG in normal young adult
and elderly subjects. Clin. Neurophysiol 2001;112:1540
1552.
29. Keshavan MS, et al. Delta sleep deficits in schizophrenia:
evidence from automated analyses of sleep data. Arch Gen
Psychia 1998;55(5):443448.
30. Keshavan MS, Reynolds CF, Miewald JM, Montrose DM. A
longitudinal study of EEG sleep in schizophrenia. Psychiat
Res 1996;59:203211.
31. Limoges E, et al. Atypical sleep architecture and the autism
phenotype. Brain 2005;128(Pt5):10491061.
32. Barry RJ, et al. Age and gender effects in coherence: II. Boys
with attention deficit/hyperactivity disorder. Clin Neurophysiol 2005;116(4):977984.
33. Cirignotta F, et al. Unreliability of automatic scoring of
MESAM 4 in assessing patients with complicated obstructive
sleep apnea syndromexd Chest. 2001;119(5):13871392.
See also ANALYTICAL METHODS, AUTOMATED; ANESTHESIA, COMPUTERS IN;
SLEEP LABORATORY.
INTRODUCTION
Spinal cord stimulation (previously known as dorsal column stimulation) is a minimally invasive technique used
primarily to treat chronic, refractory neuropathic pain. It is
based upon Melzack and Walls gate control theory (1), and
was first introduced by Shealy in 1967 (2). Neuropathic
(nerve injury) pain has many etiologies, including trauma,
stroke, diabetes, infection [e.g., human immunodeficiency
virus (HIV), or shingles], and cancer. Unfortunately, nerve
injury pain can be extremely difficult to manage. Many
types of therapy have been used for neuropathic pain
including medications such as antiinflammatories, opiates,
and antiepilepsy drugs. Physical therapy and psychologically based approaches have also been tried with variable
success. Spinal cord stimulation (SCS), transcutaneous
electrical nerve stimulation (TENS), and peripheral nerve
stimulation (PNS) are all forms of neuromodulation that
are used for nerve injury pain.
Spinal cord stimulation is typically reserved for patients
with refractory neuropathic pain, whereas deep brain stimulation is currently used for patients with movement and
some pain disorders. In SCS, a lead is percutaneously
inserted into the epidural space, and an electric field is
applied in the vicinity of the spinal cord. The electric field
depolarizes neural elements or in some way modifies the
function of the nervous system. The goal is for the patient
to experience a pleasant paresthesia, often described as
tingling, in the area of their pain. After an initial successful trial, a permanent stimulator can be implanted that the
patient controls with a hand-held device.
This article reviews the equipment used in spinal cord
stimulation, patient selection, and the possible mechanisms of this therapy. The process of inserting a stimulator
will be described with possible complications, and the
effectiveness of this therapy will be analyzed. Finally,
possible future uses of SCS will be discussed.
EQUIPMENT
Medtronic, Inc. (Minneapolis, MN), Advanced Neuromodulation Systems, Inc. (Allen, TX) and Advanced Bionics
(Valencia, CA) are the primary manufacturers of spinal
cord stimulators. There are two types of implantable leads
available: the paddle (surgical) lead and the tubular percutaneous lead (see Fig. 1). The percutaneous lead can
225
226
Figure 5. Implantable IPG with hand-held controller. (Used courtesy of Medtronic, Inc.)
PATIENT SELECTION
As noted earlier, spinal cord stimulators are used primarily
for neuropathic pain. Although there are many types of
neuropathic pain, chronic unilateral lower extremity neuropathic pain seems to respond best to this type of therapy.
A typical patient may have the failed back surgery syndrome with residual leg pain, or the patient may have some
type of neural compressive lesion that is not operable and
refractory to medical management. Spinal cord stimulation may also be indicated for chronic arachnoiditis, complex regional pain syndrome, peripheral neuropathy of the
lower limb, and phantom limb syndrome. Patients with
idiopathic pain, mechanical low back pain, or other forms of
nociceptive pain have a lower success rate when compared
to those with neuropathic conditions. Clinical experience
and studies have shown that SCS is most efficacious when
the entire painful area is covered with paresthesia. The
more diffuse the patients pain, the more difficult it will be
to cover with SCS.
Selection for SCS often includes psychological screening. Patients with untreated depression, anxiety, or drug
abuse issues are not good candidates. Obviously, the
patient needs to be able to understand how to use the
stimulator. A trial of stimulation is probably the best
predictor of long term success (4). Although the value of
227
IMPLANTATION TECHNIQUE
Before a spinal cord stimulator is implanted, the patient
needs to be informed of potential risks. These include
infection, bleeding, nerve damage, allergic reaction, and
failure of the stimulator to adequately cover or reduce the
patients pain. The patient may experience swelling around
the site of the generator and a seroma may develop requiring drainage. If the lead or the generator becomes infected,
it may have to be removed. Lead displacement, fracture, or
movement can occur such that an initially adequate pat-
228
Before
Stimulation
After
Stimulation
Pain
Tingling
SPINAL IMPLANTS
BIBLIOGRAPHY
1. Melzack R, Wall P. Pain mechanism: A new theory. Science
1965;150:951979.
229
SPINAL IMPLANTS
MICHELE MARCOLONGO
Drexel University
Philadelphia, Pennsylvania
ABHIJEET JOSHI
Abbott Spine
Austin, Texas
INTRODUCTION
Spinal implants constitute the fastest growing segment of
the orthopedic medical device industry. The area has until
230
SPINAL IMPLANTS
The intervertebral disk is basically a composite structure made up of three different tissues; the central core is
called the nucleus pulposus (Fig. 3), which is attached
radially to the multilayered fibers of the annulus fibrosus
and attached superiorly and inferiorly to cartilaginous end
plates (1). The nucleus is predominantly water in a matrix
of proteoglycan, collagen, and other matrix proteins. The
water content of the nucleus is very high at birth (approximating 90%) and then decreases through the aging cycle
down to 70% or less. The annulus surrounds the nucleus
with successive layers of tissue with collagen fibers
oriented in alternating directions. The annulus is under
tension when the nucleus absorbs water and swells. The
cartilaginous end plates have multiple perforations
that allow exchange of water and nutrients into the disk
(46).
SPINAL IMPLANTS
SPINAL DISORDERS
Various spinal disorders are observed in humans; some
manifest in pediatric patients, whereas others affect middle-aged and older patients. The most common spinal
disorders can be generally described by three different
categories: developmental bone deformities (scoliosis and
kyphosis), bone degeneration (vertebral compression fractures), and degenerative disk disease (herniation, rupture
and spinal cord stenosis).
Developmental Bone Deformities
The spine is a complex biomechanical structure and performs complex functions. This puts spine under greater
strains, and bone deformities may develop during the
course of time while performing the demanding functions
such as supporting the cranium and trunk, or absorb
stresses generated during daily physiological activities.
Most common spinal disorders under this category include
scoliosis and kyphosis.
different height shoulders, raised/prominent hip, and leaning of body to one side (7). Some causes of scoliosis include
congenital deformity, cerebral palsy, atrophy, and neuromuscular problems.
Scoliosis can either be structural or functional. Structural scoliosis is referred in case of adjacent vertebrae
rotation upon each other. This is generally followed by
deformation of rib cage. In case of functional scoliosis,
there is no fixed vertebral rotation or fixed deformity in
the thoracic region. The rate of curve progression is not
constant; however, the lumbar curves progresses more
rapidly than thoracic curves. The scoliosis is generally
classified as adolescent idiopathic scoliosis (AIS), adult
scoliosis (with or without degenerative changes), and de
novo scoliosis (which develops secondary to degenerative
changes of the lumbar spine, especially in older age) (7).
The most common tools used for diagnosis of scoliosis
include plane radiograph, computed tomography (CT)
scans, and magnetic resonance imaging (MRI). Treatment
options depend on the various factors, including the age,
curvature angle, progress rate, location, flexibility, and
spinal maturity. Conservative management (no treatment)
is commonly incorporated when the curvature is mild (less
than 208).
Orthopedic braces are recommended in case of curvature angle of 25408, to prevent further spinal deformity,
especially in children. The bracing, however, merely prevents the worsening of the existing curvature and does not
restore normal alignment (8). Many types of braces are
commercially available in the market. The brace, depending on the type and application, may extend from neck to
pelvis (Milwaukee Brace) with plastic pelvic girdle, neck
ring, and pressure pads (Fig. 4) (9), or it may just cover
below the breast to the initial pelvic region only (Boston
Brace). The use of braces has been generally effective in
case of children, to prevent the further worsening of the
scoliosis, but there is still a lack of consensus about
the indications for the brace, type, and wearing time over
the body.
Surgical options are used only in case of severe scoliosis
(curvature angle greater than 458) or for the curves that do
not respond to nonsurgical treatments. The goals of the
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232
SPINAL IMPLANTS
SPINAL IMPLANTS
loss of normal disk architecture accompanied by progressive fibrosis. At birth, the water content of the annulus
fibrosus is about 80% and that of nucleus pulposus is about
90%. Through the degenerative process, this water content
decreases to as low as 70% for the nucleus (19). Microscopic
changes such as fragmentation of fibers, mucinous degeneration of fibers leading to cyst formation, and focal aggregation of the collagen to form round aggregates of
amorphous material are observed in early stage of degeneration (20). The salient features of the DDD can be
denoted as the loss of gelatinous nucleus pulposus, gradual
disappearance of the originally well-defined border
between the nucleus and the annulus, coarsening of the
annulus lamellae, progressive fibrosis, and later fissuring
of the annulus fibrosus with the deposition of the aging
pigment (2124).
The load transfer mechanism is clearly altered in the
case of a dry nucleus. As a result, the end plates are
subjected to reduced pressure at center and more pressure
around the periphery. The stress distribution in the annulus is also altered significantly. Essentially, the nucleus
does not perform its function of load transfer and the load
transfer occurs through end plateannulusend plate
route (1). The annulus is subjected to abnormal stresses
and is more prone to injuries, and cracks/fissures first
develop into the annulus.
With continued degeneration, the central nucleus may
migrate through the crack developed in the annulus toward
the periphery. The migration of the nucleus material is
referred to as disk herniation (17). Approximately 90% of
the disk herniation would occur at the L4-L5 and L5-S1
levels. The migrated material may impinge on the nerve
root. The contact of the migrated nucleus with the nerve
root irradiates debilitating back pain. Also, the herniated
material elicits an inflammatory response because of the
avascular nature of the nucleus. It is difficult to distinguish
between the effects of aging from that of degeneration on
the biomechanical behavior of the lumbar disk. The biomechanical behavior of the disk is dependent on its state of
degeneration, which in turn depends on the age.
In case of the normal disk, any load acting on the disk is
transferred to the annulus by means of swelling pressure
(intradiscal pressure) generated by the nucleus (1). The
water binding capability of the nucleus is a function of
chemical composition of the nucleus. However, with aging
and/or degeneration, changes occur to the proteoglycans as
proteases and MMPs attack the molecules. The result is a
decrease in the proteoglycan/collagen ratio, which leads to
the lower water binding capability of the nucleus (25,26).
The load transfer mechanism in case of such a dehydrated disk is significantly altered (Fig. 5). The nucleus
cannot generate sufficient intradiscal pressure to maintain
disk height and normal mechanical function (25,27,28).
Although it is not well understood, the consequence of
the structural and mechanical changes to the disk may
be a cause of lower back pain.
Stenosis. The reduction in the disk volume leads to
instability, resulting in the growth of bone, end plates, and
ligaments to compensate for this volume loss (stenosis).
Stenosis is narrowing of the spinal canal (29). It occurs as a
233
Tensile stress
Compressive stress
234
SPINAL IMPLANTS
and/or progressive leg weakness. The indications for surgical treatment include radicular pain or neurogenic claudication with MRI or CT. In general, the goals of surgery
are pain relief, increased mobility, and improvement in the
patients quality of life. Most common surgical treatments
are laminectomy (in case of simple stenosis) and spinal
fusion. Fusion is recommended when there is a stenosis in
conjunction with
SPINAL IMPLANTS
bone over the nerve root is removed to get relief from pain.
A microscope is used to aid in visualizing the pinched nerve
and subsequent microsurgical procedure to remove the
excess portion of the herniated disk. Similarly, an open
decompression (lumbar laminectomy) is another type of
surgery that is performed to reduce the pain caused by
neural impingement, which is particularly effective as a
treatment for spinal stenosis. It is typically done with a
posterior approach. The spine is approached by cutting the
left and right back muscles off the lamina and removing the
lamina itself. The facet joints are then trimmed to allow
more space to nerve roots (30).
Even with these surgical treatments, pain may not be
relieved for disks that are more severely degenerated. In
these cases, fusion is required to restrict the motion of the
segment and thus attempt to relieve pain. A discussion of
fusion technologies and the associated implants follows.
More recent advances in non-fusion technologies are aimed
at preserving the motion segment while relieving pain.
Such non-fusion technologies include total disk replacement, nucleus replacement, and annulus repair. Numerous new companies and new medical implant strategies are
being explored currently and will hopefully prove to be
clinically relevant pain relief and function restoring solutions to DDD.
Fusion Solutions. Spinal fusion is recommended when
the discectomy approach may not be clinically relevant,
and the goal is to relieve pain by stopping the motion of a
spine segment. Spinal fusion instrumentation is essentially of three main types: pedicle screws, anterior interbody cages, and posterior lumbar cages. The bone generally
fuses more effectively when its motion is minimized; hence,
these devices are used to limit the motion of the fused
segment. Similarly, the spinal fusion is based on the
assumption that if the joint does not move, it will not create
pain.
Pedicle screws (Fig. 7) are the means of providing
anchor to the spine. They are used in combination with
the short rod to grip the spine and are made from biocompatible metals such as medical-grade stainless steel or
titanium. After a sufficient time, these screws can be
removed by doing a surgery; however, most surgeons
recommend keeping the screws unless it causes discomfort
to patient.
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236
SPINAL IMPLANTS
SPINAL IMPLANTS
237
Figure 15. Charite from Depuy Spine (33) and ProDisc from
Synthes Spine (41).
Figure 14. Infuse synthetic bone graft from Stryker Spine (36).
Bone stimulators offer another approach that potentially aid in spinal fusion. These externally applied devices
emit low electrical current (30). This is aimed at facilitating
stimulation of bone growth and increasing the chance of
achieving spinal fusion. These are used in the case of
patients who have a potentially very slow rate of obtaining
solid fusion or in the case of the revision surgery.
The fusion and discectomy relieve pain but do not
restore the normal spinal motion (37,38). The motivation
behind exploration of the new and better solutions for the
treatment of lower back pain is the failure of current
treatments (conservative and surgical) in terms of restoring the motion and normal disk biomechanics. This is
further aggravated by the complications that may occur
after the surgical treatments, such as discectomy and/or
spinal fusion.
Non-Fusion Solutions. Total disk replacement, where
an entire diseased disk is removed and replaced by a
synthetic implant, and nucleus pulposus arthroplasty,
where only the nucleus of the disk is replaced either by
a synthetic implant or recreated using tissue engineering
approach, are the emerging approaches as alternatives to
current surgical procedures for the treatment of the lower
back pain (39). Annulus repair techniques, where defects in
the annulus are either modified or repaired, also finds a
place in emerging techniques and can be potentially used
either alone or in combination with nucleus pulposus
arthroplasty procedures, depending on the degenerative
state of the intervertebral disk.
Total Disk Replacement. Total disk replacement targets
later stages of disk degeneration (Galante grade IV), where
the annulus is severely degenerated and is beyond repair
(40). The diseased disk is entirely removed and replaced by
a medical device that provides motion to the joint segment.
Disk replacement may serve to eliminate the back pain and
restore the physiological motion. A similar approach for
total knee and hip replacement is highly successful. Total
disk prostheses may be better options to spinal fusion and/
or diskectomy as it allows the physiological motion between
the adjacent vertebrae. Another advantage would be that
the effectiveness of the surgery will not be dependent on
238
SPINAL IMPLANTS
CONCLUSIONS
APPENDIX 2. TERMINOLOGY
Allograft The transplant of an organ or tissue from one
person to another.
Autograft The transplant of an organ or tissue from one
body site to another body site of the same person.
APPENDIX 1
Spinal Disorder
Treatment Options
Device/Implant
Stenosis
-Laminectomy
-Spinal fusion
-Fusion Instrumentation
Cages
Pedicle screws
Metal rod
Autograft/Allograft
Spondylolisthesis
-Laminectomy
-Spinal fusion
Fusion instrumentation
Cages
Pedicle screws
Metal rod
Autograft/Allograft
Scoliosis
-Bracing
-Spinal fusion
-Braces
-Fusion instrumentation
Cages
Pedicle screws
Metal rod
Autograft/Allograft
Kyphosis
-Balloon kyphoplasty
-Bone cement
Vertebral compression
Fracture
-Vertebroplasty
-Kyphoplasty
Disk degeneration
and herniation
-Diskectomy
-Spinal fusion
-Total disk prosthesis
-Nucleus replacement
-Fusion instrumentation
Cages
Pedicle screws
Metal rod
Autograft/Allograft
-Facet replacement
-Nucleus implant device
-Total disk arthroplasty
SPINAL IMPLANTS
Slippage
of
one
vertebra
on
239
BIBLIOGRAPHY
1. White AA, Panjabi MM. Clinical Biomechanics of the Spine.
II ed. Philadelphia: J.B. Lippincott Company; 1990.
2. http://www.ab.ust.hk.
3. http://www.spinalstenosis.org/.
4. Iatridis JC, et al. Is the nucleus pulposus a solid or a fluid?
Mechanical behaviors of the nucleus pulposus of the human
intervertebral disk. Spine 1996;21:11741184.
5. Ayad S, Weiss JB. Biochemistry of the intervertebral disk. In:
MIV J, editor. The Lumbar Spine and Back Pain. 3rd ed. New
York: Churchill-Livingstone; 1987. 100137.
6. Buckwalter JA. Aging and degeneration of the human intervertebral disk. Spine 1995;20:13071314.
7. Vaccaro A. Core Knowledge in Orthopaedics. Spine. St. Louis,
MO: CV Mosby; 2004.
8. http://www.scoliosisrx.com.
9. http://www.bostonbrace.com/ superstructure.htm.
10. MedPro Month. 1998; V.VIII:Number 1.
11. Andersson GBJ. Epidemiologic Aspects of low-back pain in
industry. Spine 1981;6(1):5360.
12. Hedman TP, et al. Design of an intervertebral disk prosthesis. Spine 1991;16(6):S256S260.
13. Cats-Baril WL, Frymoyer JW. Identifying patients at risk of
becoming disabled because of low-back painthe Vermont
Rehabilitation Engineering Center predictive model. Spine
1991;16(6):605607.
14. Sehgal N, Fortin JD. Internal disk disruption and low back
pain. Pain Physician 2000;3(2):143157.
15. Heliovaara M, et al. Determinants of sciatica and low-back
pain. Spine 1991;16(6):608614.
16. Manchikanti L. Epidemiology of low back pain. Pain Physician 2000;3(2):167192.
17. Bao QB, Yuan HA. Artificial disk technology. Neurosurgical
Focus 2000;9(4):19.
18. Bibby S, et al. The pathophysiology of the intervertebral disk.
Joint Bone Spine 2001;68:537542.
19. Vernon-Roberts B. Age-related and degenerative pathology
of intervertebral disks and apophyseal joints. In: Jayson
MIV, editor. The Lumbar Spine and Back Pain. New York:
Churchill Livingstone; 1992. 1741.
20. Vernon-Roberts B. Disk pathology and disease states. In:
Ghosh P, editor. The Biology of the Intervertebral Disk. Boca
Raton: CRC Press; 1988. 73120.
21. Coventry MB, Ghormley RK, Kernohan JW. The intervertebral disk: Its microscopic anatomy and pathology. Part III.
Pathologic changes in the intervertebral disk. J Bone Joint
Surg 1945;27A:460474.
22. Friberg S, Hirsch C. Anatomical and clinical studies on
lumbar disk degeneration. Acta Orthop Scand 1949;19:
222242.
23. Harris RI, Macnab I. Structural changes in the lumbar
intervertebral disks. Their relationship to low back pain
and sciatica. J Bone Joint Surg 1954;36B:304322.
24. Hoof VD. A: Histological age changes in the annulus fibrosus
of the human intervertebral disk. Gerontology 1964;9:136
149.
25. Bao QB, et al. The artificial disk: Theory, design and materials. Biomaterials 1996;17:11571166.
26. Akeson WH, et al. Biomechanics and biochemistry of the
intervertebral disk. Clin Orthop Rel Res 1977;129:133
139.
27. McNally DS, Adams MA. Internal Intervertebral disk
mechanics as revealed by stress profilometry. Spine 1992;
17:6673.
28. Osti OL, et al. Annular tears and disk degeneration in the
lumbar spine. J Bone Joint Surg (Br) 1992;74B:678682.
240
STATISTICAL METHODS
29. Snyder DL, Doggett D, Turkelson C. Treatment of degenerative lumbar spinal stenosis. American Family Physician
2004;70(3):517520.
30. http://www.spine-health.com.
31. http://www.texasspinecenter.com.
32. http://www.medtronic.com.
33. http://www.depuyspine.com.
34. http://www.abbottspine.com.
35. http://www.zimmerspine.com.
36. http://www.stryker.com/spine.
37. Kambin P, Savitz MH. Arthroscopic microdiscectomy: An
alternative to open disk surgery. Mount Sinai J Med 2000;
67(4):283287.
38. Weber H. Lumbar disk herniation: A controlled prospective
study with ten years of observation. Spine 1993;8:131140.
39. Joshi A. Mechanical behavior of the human lumbar intervertebral disk with polymeric nucleus implant: An experimental and finite element study. Ph.D. Thesis. Drexel
University, 2004.
40. Galante JO. Tensile properties of the human annulus fibrosus. Acta Orthop Scand 1967; (Suppl. 100):491.
41. http://www.synthes.com.
42. http://www.raymedica.com.
43. http://www.fda.gov.
See also HUMAN
OF.
STATISTICAL METHODS
ARNAUD DELORME
University of San Diego,
La Jolla, California
INTRODUCTION
Statistics can be called that body of analytical and computational methods by which characteristics of a population
are inferred through observations made in a representative
sample from that population. Since scientists rarely
observe entire populations, sampling and statistical inference are essential. Although, the objective of statistical
methods is to make the process of scientific research as
efficient and as productive as possible, many scientists and
engineers have inadequate training in experimental
design and in the proper selection of statistical analyses
for experimentally acquired data. Gill (1) states:
. . .statistical analysis too often has meant the manipulation of ambiguous data by means of dubious methods to
solve a problem that has not been defined. The purpose of
this article is to provide readers with definitions and
examples of widely used concepts in statistics. This article
first discusses some general principles for the planning of
experiments and data visualization. Then, since it is
expected that most readers are not studying this article
to learn statistics, but to find practical methods for analyzing data, a strong emphasis has been put on choice of an
appropriate standard statistical model and statistical
inference methods (parametric, nonparametric, resampling methods) for different types of data. Then, methods
for processing multivariate data are briefly reviewed. The
section following it deals with clinical trials. Finally, the
last section discusses computer software and guides the
reader through a collection of bibliographic references
adapted to different levels of expertise and topics.
STATISTICAL METHODS
DESCRIPTIVE STATISTICS
Descriptive statistics are tabular, graphical, and numerical methods by which essential features of a sample can be
described. Although these same methods can be used to
describe entire populations, they are more often applied to
samples in order to capture population characteristics by
inference.
The two main types of data samples will be differentiated: qualitative data samples and quantitative data
samples. Qualitative data arises when the characteristic
being observed is not measurable. A typical case is the
success or failure of a particular test. For example, to
test the effect of a drug in a clinical trial setting, the
experimenter may define two possible outcomes for each
patient: either the drug was effective in treating the
patient, or the drug was not effective. In the case of two
possible outcomes, any sample of size n can be represented
as a sequence of n nominal outcome x1, x2,. . ., xn that can
assume either the value success or failure.
By contrast, quantitative data arise when the characteristics being observed can be described by numbers.
Discrete quantitative data is countable, whereas continuous data may assume any value, apart from any precision
constraint imposed by the measuring instrument. Discrete
quantitative data may be obtained by counting the number
of each possible outcome from a qualitative data sample.
Examples of discrete data may be the number of subjects
sensitive to the effect of a drug (number of success and
number of failure). Examples of continuous data are
weight, height, pressure, and survival time. Thus, any
quantitative data sample of size n may be represented
as a sequence of n numbers x1, x2,. . .,xn and sample statistics are functions of these numbers.
Number of Responses
0
1
2
3
4
5
Total
38
144
342
287
164
25
1000
400
350
Number of responses
241
300
250
200
150
100
50
0
2
3
Satisfaction rank
Figure 1. Frequency histogram for the hearing aid device satisfaction survey of Table 1.
242
STATISTICAL METHODS
Table 2. Serum Calcium (mg100 mL1) in a Random Sample of 75 Week Old Infants Whose Mother Received Vitamin D
Supplement During Pregnancy
9.37
9.29
9.35
9.32
9.36
9.38
9.29
9.31
9.40
9.35
9.31
9.34
9.36
9.36
9.37
9.33
9.39
9.41
9.33
9.35
9.36
9.36
9.38
9.30
9.30
9.34
9.34
9.34
9.27
9.35
9.37
9.39
9.34
9.32
9.31
9.32
9.38
9.37
9.32
9.36
9.34
9.35
9.31
9.31
9.33
9.33
9.33
9.36
9.44
9.30
9.41
9.35
9.32
9.31
9.32
9.28
9.34
9.35
9.37
9.32
9.30
9.37
9.34
9.36
9.30
9.34
9.34
9.35
9.36
9.36
9.36
9.36
9.31
9.38
9.35
n1
i1
s2
30
25
20
15
Frequency
4
18
24
22
6
1
75
10
5
0
9.235 9.265 9.295 9.325 9.355 9.385 9.415 9.445 9.475
STATISTICAL METHODS
243
and abuse of statistics comes from the lack of understanding of its probabilistic foundation. When assumptions of
the underlying probabilistic (mathematical) model are
grossly violated, derived inferential methods will lead to
misleading and irrational conclusions. Here, only enough
probability theory to provide a framework for this article is
discussed.
In the rest of this article, experiments that have more
than one possible outcome, the actual outcome being determined by some chance mechanism will be studied. The set
of possible outcomes of an experiment is called its sample
space; subsets of the sample space are called events, and an
event is said to occur if the actual outcome of the experiment is a member of that event. A simple example follows.
The experiment will be the toss of a pair of fair coins,
arbitrarily labeled coin number 1 and coin number 2. The
outcome (1,0) means that coin No. 1 shows a head and coin
No. 2 shows a tail. Then, the sample space by the collection
of all possible outcomes can be specified:
S f0; 00; 11; 01; 1g
244
STATISTICAL METHODS
PX
X < 9:295 4=75
the ^ symbol on P indicating estimated probability
values, since actual probabilities describe the population
itself and cannot be calculated from data samples.
Similarly the probability that X is in the second bin,
x!n x!
x
(7)
STATISTICAL METHODS
1 PX < 2
see third probability definition
1 PX 0 or X 1
1PX 0 PX 1
see fourth probability definition
20
20
0:1010:9019
1
0:100 0:9020
1
0
1 0:12 0:27 0:61
x 0; 1; 2; . . .
(8)
245
continuous variables. The most important one is the normal distribution (also called LaplaceGauss distribution as
it was discovered by the French astronomer PierreSimon
Laplace and the German mathematician Karl Friedrich
Gauss in the early nineteenth century). Normal distributions arise as a result of many small random fluctuations
about some general average (e.g., repeated recordings of a
constant body temperature using a noisy electronic thermometer). A random variable X is said to be a normal or
Gaussian random variable with mean parameter m and
standard deviation parameter s if its probability density
function is
2
2
1
fX x p exm =2s
s 2p
1<x<1
(9)
(10)
0.4
0.3
0.2
0.1
0
4
3
3
2
2
1
+
2
+2
3
+3
z value
246
STATISTICAL METHODS
(12)
Mean
Variance
Binomial
Poisson
Normal
m Np
s2 Npq
ml
s2 l
m
s2
STATISTICAL METHODS
247
Table 5. Which Statistical Inference Test to Use for Which Type of Data
Dataset
Goal
Example of data sample
Binomial or
Discrete
List of patients
recovering or not
after a treatment
Proportions
x2 or Binomial test
Sign test
x2 Fishers exact test
x2 test
Cochrane Q test
Contingency coefficients
Continuous
measurement
(from a normal
distribution)
Continuous
measurement, Rank, or
Score (from nonnormal distribution)
Readings of heart
pressure from
several patients
Mean, SD
One-sample t test
Ranking of several
treatment efficiency by
one expert
Median
Sign test or
Wilcoxon test
Paired t test
Unpaired t test
Sign test or
Wilcoxon test
Mann-Whitney test
One-way ANOVAa
Kruskal-Wallis test
Repeated-measures ANOVAb
Pearson correlation
All statistical tests in this table are described in the text and often instantiated using a numerical example.
Analysis of Variance ANOVA
Friedman test
Spearman correlation
248
STATISTICAL METHODS
STATISTICAL METHODS
Table 6. Measured and Expected Frequencies of Side
Effect for 300 Children Treated With a Test Drug
Children
Expected value
13
287
300
7.5
292.5
300
Side effect
No side effects
Total
O1 e1 2 O2 e2 2
e1
e2
or more generally
x2
X Oi ei 2
i
ei
(13)
249
p 0.01
p 0.001
1df
3.84
6.64
10.83
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
35
40
50
60
70
80
90
100
5.99
7.82
9.49
11.07
12.59
14.07
15.51
16.92
18.31
19.68
21.03
22.36
23.69
25.00
26.30
27.59
28.87
30.14
31.41
32.67
33.92
35.17
36.42
37.65
38.89
40.11
41.34
42.56
43.77
49.80
55.76
67.51
79.08
90.53
101.88
113.15
124.34
9.21
11.35
13.28
15.09
16.81
18.48
20.09
21.67
23.21
24.73
26.22
27.69
29.14
30.58
32.00
33.41
34.81
36.19
37.57
38.93
40.29
41.64
42.98
44.31
45.64
46.96
48.28
49.59
50.89
57.34
63.69
76.15
88.38
100.42
112.33
124.12
135.81
13.82
16.27
18.47
20.52
22.46
24.32
26.13
27.88
29.59
31.26
32.91
34.53
36.12
37.70
39.25
40.79
42.31
43.82
45.32
46.80
48.27
49.73
51.18
52.62
54.05
55.48
56.89
58.30
59.70
66.62
73.41
86.66
99.62
112.31
124.84
137.19
149.48
4:13
7:5
292:5
with 1 degree of freedom (2 rows minus 1). For a test at the
5% level of significance (p 0.05) with 1 degree of freedom,
x2crit in the x2 table (Table 7) is equal to 3.84. Since
4.13 > 3.84, the hypothesis that the proportion of children
having side effects in the same as that of adults is rejected.
Comparing actual and expected frequencies in Table 6, we
conclude that children have higher occurrences of side
effects than adults for this drug.
Note that the construction of the x2 table is relatively
simple. One can simply assume that a known population
(whose expected distribution is known) is sampled several
times and that the x2 value is computed for each of these
samples. The histogram of these observed x2 values, when
in fact no real effects are present, is an approximation to
the x2 distribution for the null hypothesis (Fig. 4). The tails
of this distribution may be used to set thresholds for
significance testing (if an observed x2 value ends up in
the tail of the distribution, then it is likely that it does not
originate from the known population). For example, the x2
To use this table, choose a p value (column) and read the value for your
calculated degrees of freedom (df). If your calculated x2 value is larger than
the one you read in the table, the test you performed is significant (see text
for details).
250
STATISTICAL METHODS
0.2
0.4
2 dist. df = 5
0.1
0.2
10
PX 9 PX 9 PX 10
0.4
0
10
20
10
5% of area
10
or more is
F dist.
df n = 5
df d =10
2.5% of
area
2.5% of
area
5% of area
0.8
t dist.
df = 5
10
0:59 1 0:5109
9
10
0:510 0:011
10
1 0:571 0:45
Table 8. Success () or Failure () of Drug A and B for Reducing Pain in 10 Patients
Patient
10
Drug A
Drug B
Sign
STATISTICAL METHODS
251
Table 9. Results of Improvement in Muscular Response Following Implantation of an Electronic Device Available in Four
Types
Type of Device
No improvement
Partial-to-full restoration
Total
Total
35(30)a
65(70)
100
40(30)
60(70)
100
35(30)
65(70)
100
10(30)
90(70)
100
120
280
400
Numbers are observed frequencies and number in parentheses are expected frequencies.
As for the simpler example earlier in this section comparing a sample data distribution to a theoretical distribution, the x2 is simply calculated by comparing the expected
frequencies, denoted by ei,j for device i (where i ranges from
1 to 4) and outcome j (where j 1 indicates no restoration
and j 2 indicates partial to full restoration), to the
observed frequencies Oi,j using the formula:
X
x2
Oi j ei j 2 =ei j
(14)
i; j
26:2
30
70
30
is given by
s
x2
r
NminNo: rows; No: columns 1
(15)
252
STATISTICAL METHODS
0.1
0.05
0.025
0.01
0.005
0.0001
Two-Tailed
0.2
0.1
0.05
0.02
0.01
0.0002
3.078
1.886
1.638
1.533
1.476
1.440
1.415
1.397
1.383
1.372
1.363
1.356
1.350
1.345
1.341
1.337
1.333
1.330
1.328
1.325
1.323
1.321
1.319
1.318
1.316
1.315
1.314
1.313
1.311
1.310
1.303
1.295
1.296
1.292
1.290
1.282
1.282
6.314
2.920
2.353
2.132
2.015
1.943
1.895
1.860
1.833
1.812
1.796
1.782
1.771
1.761
1.753
1.746
1.740
1.734
1.729
1.725
1.721
1.717
1.714
1.711
1.708
1.706
1.703
1.701
1.699
1.697
1.684
1.676
1.671
1.664
1.660
1.646
1.64
12.71
4.303
3.182
2.776
2.571
2.447
2.365
2.306
2.262
2.228
2.201
2.179
2.160
2.145
2.131
2.120
2.110
2.101
2.093
2.086
2.080
2.074
2.069
2.064
2.060
2.056
2.052
2.048
2.045
2.042
2.021
2.009
2.000
1.990
1.984
1.962
1.960
31.82
6.965
4.541
3.747
3.365
3.143
2.998
2.896
2.821
2.764
2.718
2.681
2.650
2.624
2.602
2.583
2.567
2.552
2.539
2.528
2.518
2.508
2.500
2.492
2.485
2.479
2.473
2.467
2.462
2.457
2.423
2.403
2.390
2.374
2.364
2.330
2.326
63.66
9.925
5.841
4.604
4.032
3.707
3.499
3.355
3.250
3.169
3.106
3.055
3.012
2.977
2.947
2.921
2.898
2.878
2.861
2.845
2.831
2.819
2.807
2.797
2.787
2.779
2.771
2.763
2.756
2.750
2.704
2.678
2.660
2.639
2.626
2.581
2.576
318.3
22.33
10.21
7.173
5.893
5.208
4.785
4.501
4.297
4.144
4.025
3.930
3.852
3.787
3.733
3.686
3.646
3.611
3.579
3.552
3.527
3.505
3.485
3.467
3.450
3.435
3.421
3.408
3.396
3.385
3.307
3.261
3.232
3.195
3.174
3.098
3.091
df
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
40
50
60
80
100
1000
inf.
a
To use this table, find your degrees of freedom in the df column (or a lower one if yours is not present in the table). Then, look up the probability in the top row
(p 0.05 is a test of significance at 5%). If your calculated t value is larger than the one you read in the table, the test you performed is significant (see text for
details).
M m p
N
SD
16
As for the x2 table, building the t-test table is straightforward. One may assume that, for a given degree of freedom, a known population (with a normal distribution) is
sampled several times and that the t value is computed for
each of these samples (M should on average be the same as
m since it is the theoretical population which is being
sampled). The histogram of these observed t values,
obtained when in fact no real effects are present, is an
approximation to the t distribution (Fig. 4, middle panel).
The tails of this distribution allow for threshold setting for
significance (as for the x2, if an observed value ends up in
the tail of the distribution, then it is likely that it does not
belong to this distribution). Note that for an infinite
number of degrees of freedom, the t distribution is equal
to the normal distribution.
For example, in the past, a machine has been producing
washers having a thickness of 0.06 in. (0.15 cm) on average.
STATISTICAL METHODS
0:0625 0:06 p
10 3:16
0:0025
Dav p
N
SD
17
253
2:8 p
10 3:44
2:57
VA NA 1 VB NB 1
NA NB 2
18
MA MB
SE
20
Table 11. Systolic Blood Pressure in Hgmm Measured in 10 Patients Using Either a New Electronic Device or an Old
Manual Device
Patient
Electronic BP device
Manual BP device
10
121
115
130
131
129
127
113
111
145
140
132
131
110
111
116
111
125
121
155
150
254
STATISTICAL METHODS
Table 12. Heart Rate in Beats per Second of Control and Test Patients Suffering from Heart Failure
HF patients
Control patients
78
80
81
71
88
68
76
80
88:4 77:7
2:17
4:93
VinterGroup
VwithinGroup
(21)
93
95
112
67
83
85
96
69
85
77
0:44
0:49
0:89
STATISTICAL METHODS
255
Table 13. The F Distribution of Critical Values at p 0.05 for ANOVA testsa
df2\df1
10
12
15
20
30
40
60
100
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
22
24
26
28
30
35
40
45
50
60
70
80
100
200
500
1000
1
10.13
7.71
6.61
5.99
5.59
5.32
5.12
4.96
4.84
4.75
4.67
4.60
4.54
4.49
4.45
4.41
4.38
4.35
4.30
4.26
4.23
4.20
4.17
4.12
4.08
4.06
4.03
4.00
3.98
3.96
3.94
3.89
3.86
3.85
3.84
9.55
6.94
5.79
5.14
4.74
4.46
4.26
4.10
3.98
3.89
3.81
3.74
3.68
3.63
3.59
3.55
3.52
3.49
3.44
3.40
3.37
3.34
3.32
3.27
3.23
3.20
3.18
3.15
3.13
3.11
3.09
3.04
3.01
3.00
3.00
9.28
6.59
5.41
4.76
4.35
4.07
3.86
3.71
3.59
3.49
3.41
3.34
3.29
3.24
3.20
3.16
3.13
3.10
3.05
3.01
2.98
2.95
2.92
2.87
2.84
2.81
2.79
2.76
2.74
2.72
2.70
2.65
2.62
2.61
2.61
9.12
6.39
5.19
4.53
4.12
3.84
3.63
3.48
3.36
3.26
3.18
3.11
3.06
3.01
2.96
2.93
2.90
2.87
2.82
2.78
2.74
2.71
2.69
2.64
2.61
2.58
2.56
2.53
2.50
2.49
2.46
2.42
2.39
2.38
2.37
9.01
6.26
5.05
4.39
3.97
3.69
3.48
3.33
3.20
3.11
3.03
2.96
2.90
2.85
2.81
2.77
2.74
2.71
2.66
2.62
2.59
2.56
2.53
2.49
2.45
2.42
2.40
2.37
2.35
2.33
2.31
2.26
2.23
2.22
2.21
8.94
6.16
4.95
4.28
3.87
3.58
3.37
3.22
3.09
3.00
2.92
2.85
2.79
2.74
2.70
2.66
2.63
2.60
2.55
2.51
2.47
2.45
2.42
2.37
2.34
2.31
2.29
2.25
2.23
2.21
2.19
2.14
2.12
2.11
2.10
8.89
6.09
4.88
4.21
3.79
3.50
3.29
3.14
3.01
2.91
2.83
2.76
2.71
2.66
2.61
2.58
2.54
2.51
2.46
2.42
2.39
2.36
2.33
2.29
2.25
2.22
2.20
2.17
2.14
2.13
2.10
2.06
2.03
2.02
2.01
8.85
6.04
4.82
4.15
3.73
3.44
3.23
3.07
2.95
2.85
2.77
2.70
2.64
2.59
2.55
2.51
2.48
2.45
2.40
2.36
2.32
2.29
2.27
2.22
2.18
2.15
2.13
2.10
2.07
2.06
2.03
1.98
1.96
1.95
1.94
8.81
6.00
4.77
4.10
3.68
3.39
3.18
3.02
2.90
2.80
2.71
2.65
2.59
2.54
2.49
2.46
2.42
2.39
2.34
2.30
2.27
2.24
2.21
2.16
2.12
2.10
2.07
2.04
2.02
2.00
1.97
1.93
1.90
1.89
1.88
8.79
5.96
4.74
4.06
3.64
3.35
3.14
2.98
2.85
2.75
2.67
2.60
2.54
2.49
2.45
2.41
2.38
2.35
2.30
2.25
2.22
2.19
2.16
2.11
2.08
2.05
2.03
1.99
1.97
1.95
1.93
1.88
1.85
1.84
1.83
8.74
5.91
4.68
4.00
3.57
3.28
3.07
2.91
2.79
2.69
2.60
2.53
2.48
2.42
2.38
2.34
2.31
2.28
2.23
2.18
2.15
2.12
2.09
2.04
2.00
1.97
1.95
1.92
1.89
1.88
1.85
1.80
1.77
1.76
1.75
8.70
5.86
4.62
3.94
3.51
3.22
3.01
2.85
2.72
2.62
2.53
2.46
2.40
2.35
2.31
2.27
2.23
2.20
2.15
2.11
2.07
2.04
2.01
1.96
1.92
1.89
1.87
1.84
1.81
1.79
1.77
1.72
1.69
1.68
1.67
8.66
5.80
4.56
3.87
3.44
3.15
2.94
2.77
2.65
2.54
2.46
2.39
2.33
2.28
2.23
2.19
2.16
2.12
2.07
2.03
1.99
1.96
1.93
1.88
1.84
1.81
1.78
1.75
1.72
1.70
1.68
1.62
1.59
1.58
1.57
8.62
5.75
4.50
3.81
3.38
3.08
2.86
2.70
2.57
2.47
2.38
2.31
2.25
2.19
2.15
2.11
2.07
2.04
1.98
1.94
1.90
1.87
1.84
1.79
1.74
1.71
1.69
1.65
1.62
1.60
1.57
1.52
1.48
1.47
1.46
8.59
5.72
4.46
3.77
3.34
3.04
2.83
2.66
2.53
2.43
2.34
2.27
2.20
2.15
2.10
2.06
2.03
1.99
1.94
1.89
1.85
1.82
1.79
1.74
1.69
1.66
1.63
1.59
1.57
1.54
1.52
1.46
1.42
1.41
1.40
8.57
5.69
4.43
3.74
3.30
3.01
2.79
2.62
2.49
2.38
2.30
2.22
2.16
2.11
2.06
2.02
1.98
1.95
1.89
1.84
1.80
1.77
1.74
1.68
1.64
1.60
1.58
1.53
1.50
1.48
1.45
1.39
1.35
1.33
1.32
8.55
5.66
4.41
3.71
3.27
2.97
2.76
2.59
2.46
2.35
2.26
2.19
2.12
2.07
2.02
1.98
1.94
1.91
1.85
1.80
1.76
1.73
1.70
1.63
1.59
1.55
1.52
1.48
1.45
1.43
1.39
1.32
1.28
1.26
1.25
8.54
5.63
4.36
3.67
3.23
2.93
2.71
2.54
2.41
2.30
2.21
2.13
2.07
2.01
1.96
1.92
1.88
1.84
1.78
1.73
1.69
1.66
1.62
1.56
1.51
1.47
1.44
1.39
1.35
1.33
1.28
1.19
1.12
1.08
1.03
To use this table, read the value at the intersection of the numerators degrees of freedom (df1) and the denominators degrees of freedom (df2). If your
calculated F value is larger than the one you read in the table, the test you performed is significant (see text for details).
VinterGroup
Verror
24
25
where xjk are all the elements in the array, M j: are the row
means, M:k are the column means, M is the global array
mean, NC is the number of columns, and NR the number of
rows. The degrees of freedom for the numerator and
0:44
0:42
1:04
Table 14. Signal/Noise Ratio for 10 Patients and for Three Brands of EEG Systems
Brand A
Brand B
Brand C
1.87
2.48
2.29
3.88
1.71
1.49
2.68
3.05
2.52
1.19
1.58
1.26
0.93
1.7
3.71
0.38
3
2.14
2.69
0.47
2.33
1.8
2.11
2.79
0.39
2.18
2.61
1.62
2.22
0.29
256
STATISTICAL METHODS
Brand B
Brand C
6
10
10
2
6
6
6
6
4
8
8
6
2
10
2
0
4
8
Protocol 2
8
2
2
10
10
6
4
4
8
1
2
1
4
5
3
5
1
3
Protocol 3
0
0
3
9
5
7
3
1
3
2
1
3
8
9
7
2
1
2
1
4
3
3
5
3
6
6
4
4
2
5
3
4
5
6
0
8
4
2
0
6
2
6
8
10
6
test. For example, there are different ways to treat multifactor ANOVAs analytically when the number of observations is unequal among the treatment combinations (called
unbalanced designs). A nontechnical discussion is the
classic Planning of Experiments by Cox (6). Other general
introductions are Refs. (1,712).
Regression and Correlation. Regressions and correlations aim at determining relationship between variables.
We may wish to determine if there is a significant correlation between independent and dependent variables, the
independent variable being set by the experimenter, and
the dependent variable being measured. For example, to
test the reliability of a device, an experimenter may
change the temperature of the room where the device is
being tested (independent variable), and see if this change
affects measures returned by the tested device (dependant variable). Regression and correlation can also be
used to estimate the relationship between two (or more)
dependent variables.
The first step in determining the relation between two
variables is to plot values of one variable versus values of
the other variable. This is usually called a scatterplot
(Fig. 5). From the scatterplot it is often possible to visualize a smooth curve that approximates the data. If it is a
straight line, then the least-squares regression method
may be used. Otherwise, other curve fitting procedures
may be used. It is sometimes useful to plot scatterplots of
transformed variables (e.g., log transformation of values
the in first variable versus values of the second variable).
The method of least-squares computes the best linear
regression between two variables. Specifically, for two
variables X and Y, the data consist of n pairs (x1,
y1),. . .,(xn, yn). For all values of X and Y, we wish to find
the parameter a and b such that
Y aX b
(26)
P
P
xi yi xi yi
P
P
N x2i xi 2
X
1
X
yi a
xi
N
(27)
(28)
STATISTICAL METHODS
1.6
Y = 0.924X + 0.534
1.4
r2 = 0.892
1.2
Variable Y
1
0.8
0.6
0.4
0.2
0
0
0.2
0.4
0.6
Variable X
257
0.8
q
q
r
Pn
SDX :SDY
2 1 Pn
2
1
x
M
X
i1 i
i1 yi MY
n
n
(30)
where MX and MY (SDX and SDY) are the mean (the
standard deviation) for X and Y, respectively, and cov(X,Y)
is the covariance between X and Y (the numerator on the
right of Eq. 30 is equal to cov(X,Y) and the denominator is
equal to SDX SDY). Necessarily 1 r 1. Positive
(respectively negative) values of r indicate that large
values (respectively small values) of X are associated with
large values (respectively, small values) of Y. Values of r
near 0 indicate little or no linear association. Interpretation must be done with care because there are many
reasons for the presence or absence of a correlation. Also,
comparing r values may be misleading as a value of r 0.6
does not mean that the linear relationship is twice as
strong as r 0.3. On the other hand, r2, called the sample
coefficient of determination, represents the proportion of
the total variation in the sample values of Y that can be
explained by a linear relationship as in Eq. 26. Thus
r2 (0.3)2 0.09 versus r2 (0.6)2 0.36 indicates a 9%
258
STATISTICAL METHODS
Table 16. Heart Rate Variability for 10 Patients While Their Pacemaker Is Switched On or Off, and Calculation of Signed
Rank for Wilcoxon Test
Patient
Pacemaker off
Pacemaker on
difference
abs difference
Rank of abs difference
Signed rank
10
Sum
0.15
0.12
0.03
0.03
1.5
1.5
0.32
0.19
0.13
0.13
4
4
0.25
0.28
0.03
0.03
1.5
1.5
1.1
0.56
0.54
0.54
9
9
0.82
0.37
0.45
0.45
7
7
0.83
0.52
0.31
0.31
5
5
0.94
0.24
0.70
0.70
10
10
0.42
0.73
0.51
0.51
8
9
0.48
0.81
0.43
0.43
6
6
0.21
0.13
0.08
0.08
3
3
23
goodness-of-fit test may be used on the frequency distribution (histogram) of the data compared to a hypothetical
distribution.
In fact,
W
SDW
(32)
NA NA 1
RA
2
(34)
Table 17. Patient Maximal Sensitivity (in dB) for Two Brands of Hearing Aids
Brand A
Brand B
0.1
2.7
1
3.1
4.1
5.2
2.4
2.1
2.3
4.7
3.8
1.5
0.9
1.2
1.4
3.7
0.4
2.8
1.2
3.1
STATISTICAL METHODS
259
4
12
3
14.5
18
20
11
10
1
19
NB 10, so
1010 1
80 75
2
There is no table for U values. Instead, as for the
Wilcoxon test, the table for z values is used because of a
property of the U distribution. When calculating the U
value repeatedly on samples known not to be statistically
different (e.g., two data samples drawn from the responses
of the same device), then it can be shown that the repeated
U values (U1, U2, U3, . . .) have a Gaussian distribution
with mean MU and standard deviation SDU defined as
U 10 10
NA NB
2
(35)
r
NA NB NA NB 1
12
(36)
MU
SDU
(37)
3N 1 (38)
H
NN 1 NA NB NB
It can be shown that, after collecting repeated measures
of H from several samples from the same population (verifying the hypothesis H0 that they originate from the same
population), the histogram of H values is very close to a x2
distribution with degrees of freedom equal to the number of
groups minus one (so the x2 table may be used for H). Thus,
17
9
6
2
8
16
5
13
7
14.5
TA 2 TB 2 TC 2 Tall 2
NG
NG N
(39)
SS
NG NG 1=12
(40)
6D1 2 D2 2 D3 2
NN 2 1
(41)
STATISTICAL METHODS
Bootstrap t-distribution
1000
# of values per bin
800
600
2.13
400
200
0
0
1
t-value
Randomized t-distribution
1000
# of values per bin
260
800
600
2.11
400
200
0
0
t-value
Figure 6. Bootstrap t-distribution for Table 12 (top) and randomized t-distribution for Table 12 (bottom). Since the actual t-value
obtained from the original samples in Table 12 (t 2.17) belong to
the rightmost 2.5% value in both the bootstrap and the randomized
distribution (the 2.5% limit being indicated by a vertical line), it
may be considered significant at 5%.
STATISTICAL METHODS
This procedure may be generalized to compare an arbitrary number of samples. For example, to compare several
unpaired sample, data sample values may be randomized
among groups and one-way ANOVA values may be calculated repeatedly. The ANOVA value for the nonrandomized
groups is then compared against this ANOVA randomized
distribution. Web Ref. 18 provides a clear introduction to
resampling methods.
the same as for the bootstrap and involves a vague formulation about the result of the experiment, such as
patient suffering from heart failure have abnormal heart
rate or the drug treatment does not have an effect on
blood pressure.
Randomizing the data is straightforward. Using the
same example as for the bootstrap distribution with two
unpaired samples A and B of sizes NA and NB, a randomization method consists of pooling the data of A and B
together (into C), then randomly drawing from C (without
replacement) two groups A0 and B0 that have the same size
as A and B, respectively (17). Then, compute the estimator
(e.g., t-value) for each randomized pair of samples. Repeat
this procedure a large number of times to obtain the
distribution of the estimator (e.g., t-value) for the null
hypothesis. Significance is assessed as for the bootstrap
t-test. For example, in Fig. 6 (bottom), 10,000 randomized
t-values have been accumulated for the two samples in
Table 12. Note that irregularities in the distribution are
due to the fact that we are randomizing a relatively small
number of values. As for the bootstrap, since the original
t-value (t 2.17) lies in the upper 2.5% of the randomized tvalues, it may be concluded that the data support the
hypothesis that heart rate is affected in patients suffering
from heart failure at the 5% significance level. It is reassuring to notice that the upper 5% significance threshold tvalue for the bootstrap (tcrit 2.13), the randomized
(tcrit 2.11), and the normal distribution (tcrit 2.12) are
all similar.
For paired comparisons, the principle is slightly different since we are now randomizing not the sample values
but the pairs. For example, for the data of Table 11, onehalf of the pairs are selected randomly then shuffled (the
value for the first device is now attributed to the second
device and vice versa) and the paired t-test value is recalculated (Eq. 17). This procedure is repeated many times. To
assess significance, as in the previous paragraph, the
original t-value computed using the nonrandomized samples is compared against the distribution of randomized
t-value.
MULTIVARIATE METHODS
Previously the probability distributions involving one variable were discussed, but in many situations there are two
or perhaps many interdependent variables, for example,
height, weight, daily caloric intake, genetic strain. Data
samples involving several variables are called multivariate. Many multivariate analytical methods involve inference for the parameters (means, variances, and correlation
coefficients) based on multivariate normal distribution.
One such method is known as discriminant analysis and
is concerned with the problem of distinguishing between
two or more populations on the basis of observations of a
multivariate nature. Principal components analysis, cluster, and factor analysis seek to determine relatively few out
of possibly many variables that will serve to explain the
variability or the interrelationships in the variables. Principal component analysis (PCA) would specifically make
each successive component account for as much as possible
of the remaining variability uncorrelated with previously
determined components. In Fig. 7, data points from two
variables are represented. Coordinates of data points on
the abscissa axis correspond to values of the first variable
and coordinates on the ordinate axis correspond to values
of the second variable. The PCA is able to find a first
principal axis (labeled one) that accounts for most of the
variance of the data. The second principal axis (labeled
two) has to be perpendicular to the first principal axis and
accounts for the remaining of the variance.
Recent progresses in signal processing and information theory have seen the development of blind source
2
1.5
PCA
1.5
Variable 2
0.5
0
0
1
0.5
1
1
1.5
3
ICA
0.5
0.5
0
1
Variable 1
261
1.5
3
0
1
Variable 1
Figure 7. Illustration of PCA and ICA algorithms. The PCA finds axis with maximum variance. By
contrast in ICA, the projection of data point on ICA axis is maximally independent.
262
STATISTICAL METHODS
STATISTICAL METHODS
263
264
STATISTICAL METHODS
REFERENCES USED
This list is not meant to be comprehensive. For the nave
reader, a basic introduction to statistics with a plethora of
exercises is given in the Schaums outline series on statistics (2). For the nonnave reader in statistics, a more
technical yet still accessible reference is Ref. 30. Other
texts dealing with general statistical methods, particularly regression and analysis of variance are Refs. 31 and
32. Comprehensive web references are Refs. 18, 33,
and 34.
Statistical books have also been written for specific
research topics. For example, see Ref. 35 for a beginners
reference in designing biology experiments and Refs. 6, 8
10 for more detailed references. As already mentioned, see
Refs. 28, 29, 36, and 37 for clinical trials. Finally, a recent
development in statistics is statistical process control that
deals with optimizing production and quality in the industry (38).
ACKNOWLEDGMENTS
Parts of this article were adapted from a previous version of
this encyclopedia paper by P. Sullo and L.E. Ostrander
from the Rensselaer Polytechnic Institute. The author also
wishes to thank anonymous reviewer for their invaluable
comments.
BIBLIOGRAPHY
1. Gill JL, Design and Analysis of Experiments in the Animal
and Medical Sciences. Ames (IA): Iowa State University
Press; 1978.
2. Spiegel MR, Stepens LJ, Schaums Outlines in Statistics. 3
ed. New York: McGraw Hill; 1999.
3. Bonferroni CE. Sulle medie multiple di potenze, Bollettino
dellUnione Matematica Italiana, 5 third series, 1950. p 267
270.
4. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat 1979;6, 6570.
5. Hoppe F. Multiple Comparisons, Selection, and Applications
in Biometry: A Festschrift in Honor of Charles W. Dunnett.
New York: Marcel Dekker; 1992.
6. Cox DR. Planning of Experiments. New York: John Wiley &
Sons; 1992.
7. Norman R, Draper NR, Smith H. Applied Regression
Analysis. 2nd ed. New York: John Wiley & Sons;
1998.
8. Lorenzen TJ, Anderson VL. Design of Experiments: A NoName Approach. New York: Dekker; 1993.
9. Box GEP, Hunter WG, Hunter JS. Statistics for Experimenters. New York: John Wiley & Sons; 1978.
10. Cochran WG, Cox GM. Experimental Designs. New York:
John Wiley & Sons; 1992.
11. Hicks CR, Turner KV. Fundamental Concepts in the
Design of Experiments. New York: Oxford University Press;
1999.
STEREOTACTIC SURGERY
265
STEREOTACTIC.
STEREOTACTIC SURGERY
ANTONIO A.F. DE SALLES
ALESSANDRA GORGULHO
UCLA Medical School
Los Angeles, California
INTRODUCTION
Stereotactic surgery evolved from the need of neuroscientists and neurosurgeons to approach areas deep in the
brain with minimal disruption of its structure. In
(1000 AD, the Incas already had some idea of which
regions of the brain could be operated on without causing
detectable functional deficits (1). They concentrated their
trepanations in the right frontal area knowing that lesions
in this region of the brain would be safe (2). The scientific
literature, however, registers the first minimally invasive
attempt to approach the noneloquent areas of the brain in
the late 1800s. Zernov, a Russian anatomist, described the
first device used to localize the sensory-motor areas of the
brain (3,4) This device allowed the surgeon to use noneloquent areas as approaches to targets in the depth of the
brain. He designed a frame that was attached to the
patients head and supported a hemisphere with a drawing
of the brain gyri. This drawing guided the surgeon where to
perform the craniotomy avoiding eloquent areas (4). This
device was crude, however, and needed to be replaced by a
precision instrument capable of being applied to patients
individual anatomy and not on a generic drawing.
Cartesian coordinates, developed by Renee Descartes
(5), were called upon to guide the neurosurgeons in their
endeavor. Initially developed for use in laboratory animals,
the first stereotactic frame based on Cartesian spatial
localization was designed by an electrophysiologist and a
neurosurgeon. The Cartesian system provides precise localization of a point in space by the distance that the point is
located from each of the three planes. Clarke and Horsley
applied a stereotactic frame in animals to guide electrodes
into the depth of the cerebellum to study neuronal function
(6,7) (Fig. 1). This apparatus inspired the Canadian bioengineer Aubrey Mussen to develop the first true stereotactic
device for humans (8,9). This device was never applied to a
patient, since Mussen could not convince any neurosurgeon in Canada to use it. It is believed to have been created
1918, as it was found several years later wrapped in a
newspaper of that year. It is currently in exhibit at the
Montreal Neurological Institute (10).
All early localization of brain structures was based on
cranial landmarks. Unfortunately, these bony reference
points frequently failed to guide the surgeon to the precise
area of the brain to be approached. Only when angiography
(11) and ventriculography (12,13) became available, stereotactic surgery based on intracranial reference points
Figure 1. A. HorsleyClark stereotactic device: Horsley, a neurosurgeon and Clark, a physiologist, developed the first stereotactic apparatus. It was used in experimental studies in animals.
266
STEREOTACTIC SURGERY
STEREOTACTIC SURGERY
267
resolution, excellent soft tissue contrast, absence of ionizing radiation, and bony artifact on adjacent soft tissue (40).
These characteristics made MRI attractive for framed
procedures and also enabled the use of MRI in frameless
guided procedures (Fig. 4).
However, there are some disadvantages. The MRI is
more prone to geometric distortion than CT. The maximum
localization error reported in the literature ranges from 1
to 5 mm (33,40). The variation in the maximum error may
be accounted for partly by the use of different stereotactic
systems and different reference imaging modalities to
which MRI is compared. Actually, the geometrical accuracy
of MRI is not significantly different from the accuracy of
conventional stereotactic frames (41,42). The spatial accuracy of MRI depends on the linearity and calibration of
magnetic field gradients and on magnetic susceptibility
artifacts that manifest as spatial distortions. Meticulous
Figure 4. View of the UCLA interventional MRI (Sonata, Siemens, Erlangen, Germany) operating room.
268
STEREOTACTIC SURGERY
Indication
Behavior
Amygdalotomy
Anterior capsulotomy
Cingulotomy
Posteriormedial Hypothalamotomy
Subcaudate tractotomy
Violence, aggressiveness
Obsessive compulsive disorder (OCD)
Anxiety, depression, OCD
Aggressiveness
Anxiety with depression
Pain
Cingulotomy
Dorsomedian thalamotomy
Pulvinotomy
Mesencephalotomy
Periaqueductal stimulation
Periventricular stimulation
Cortical stimulation
Ventrolateral thalamotomy
Pallidotomy
Campotomy (Forels fields)
Zona incerta
Dentatotomy
Striatum fetal tissue transplant
Amygdalofornicotomy/anterior Commissurotomy
Pallidoamygdalotomy or Centromedian lesion
Deep electrode
STEREOTACTIC SURGERY
Table 2
Stereotactic Craniotomy
Morphologic
Functional
Diagnostic
Stereotactic biopsy
Diagnostic
Deep electrode for seizure focus
determination
Therapeutic
Therapeutic
Radiosurgery
Frameless
neuronavigation
Hyperthermia
Stereotactic craniotomy
Brachytherapy
a
269
Stereotatic Biopsy
The determination of the biopsy target follows the same
targeting procedure described above, however, electrophysiology is not used for confirmation. Instead, the histology
obtained with a frozen section confirms the adequacy of the
target.
Once the patient has the burr hole placed, the needle
biopsy is introduced through the driver attached to
the frame arc. The planning is established based on the
three plan views: axial, coronal, and sagital. Samples of
tissue are collected and frozen pathology is performed.
After obtaining histological diagnosis, the operative wound
is closed and the patient is submitted to a postoperative
MRI. Usually an air bubble is observed at the site of the
biopsy, confirming the target (28). Pre- and postoperative
images are fused. Minimally invasive approaches to vital
structures, such as brainstem, became possible only after
the development of high definition imaging methods (Fig. 5).
Radiosurgery
Radiosurgery is likely the most frequent reason for stereotactic frame application nowadays. Under local anesthesia,
a CRW (Radionics, Burlington, MA) or SRS frame (BrainLab, Heimstetten, Germany) is attached to the patients
head. The patient is submitted to a CT scan and the CTframed image is fused to the preoperative MRI. The planning starts by the drawing of the lesion, that is, in reality,
the target determination. After conclusion of the planning,
the patient is attached to a Novalis (BrainLab, Heimstetten, Germany) couch. Focused radiation is delivered with
high precision achieved with frame-based spatial localization. At the end of the treatment, the frame is removed. In
SRT cases, since the placement of a frame for 2630 times
in a patient is impracticable, a facial mask is manufactured. The frame and the fiducials are applied to the mask.
The patient undergoes CT, which is fused with the MRI
previously obtained. The reproducibility of accuracy with
the facial mask, on a daily basis, has already been demonstrated to be 2 mm (Solberg, personal communication).
New radiosurgery devices, as Novalis and Cyberknife,
allow the use of this frameless technique for radiosurgery
of extracranial targets.
270
STEREOTACTIC SURGERY
is variable depending on age, brain atrophy, and positioning for the procedure (50,75). This dynamic brain shifts can
be overcome by real-time imaging during surgery.
Interventional MRI
New open designs of MR scanners with in-room image
monitors allow MRI-guided interventional procedures.
(Fig. 4) The first step toward practical interventional
MRI of the brain is the development of instruments that
function satisfactorily and safely in the strong magnetic
field of clinical MRI scanners. Some concerns derive from
this assertive.
Traditionally, surgical instruments are made of stainless steel material. Susceptibility artifacts usually develop
at the extremities of the instrument. At the moment,
considerable effort has been converged to test different
biomaterials in the MRI magnetic field. The goal is to
define the most suitable material: minimal artifact and
high resistance. Less artifact is produced by ceramics,
zirconium seems to produce the smallest artifact among
the ceramics (76). On the other hand, ceramics present
lower retention force and lower flexibility when compared
to metallic materials. Susceptibility artifacts are also
dependent on the pulse sequence applied. Spin echo
sequences are less sensitive to time-independent local
magnetic field variations while gradient spinecho
sequences are more susceptible to time-dependent and
time-independent local field changes.
The strength of the magnetic field also interferes with
the degree of distortion. It is possible to minimize significantly the amount of distortion using a short echotime,
thinner slices, small field of vision (FOV) and higher readout gradients. Any material used in manufacturing the
instruments will produce some amount of artifacts.
The actual location of the instrument, for example, an
electrode inside the artifact, is another important issue.
This becomes important to evaluate the final placement of
the electrode according the planned target comparatively.
It is known that artifacts develop parallel to the direction of
the main magnetic field applied. The precise position of the
electrode inside the distorted image was reported to be in
the middle of the artifact (77).
Another concern is related to electromagnetic interference between the MRI scanner and interventional electronics. For example, the rf generator may emit
electromagnetic radiation that interferes with image
acquisition and generates artifacts. At UCLA, the use of
MER in the MRI is routine, either the 0.2 (70) or the 1.5 T
(Siemens, Erlangen, Germany), with special attention to
work in the fringes of the strong magnetic field. Interferences can be safely avoided in so far as attention is centered
in the strategic location of the devices inside the MRI room.
To approximate real-time imaging, either image acquisition or image reconstruction has to be of very high speed.
Currently, millimetric resolution in the 0.2 T and submillimetric in the 1.5 T can be achieved with the parameters
reported at Table 3.
Interventional MRI scanners offer the possibility of
image acquisition in advance for planning the procedure,
intraoperatively for compensation of brain shift that occurs
STEREOTACTIC SURGERY
271
3 DF
WB
56
25
280
256 256
1:1 1:1 3:0
7 : 42
T2W TSE
BG
2800
84
280
256 256
1:1 1:1 2:0
2 : 47
FL 2D
WB
800
15
280
168 256
1:5 1:1 7:0
4 : 28
T1W T1 weighed. TSE turbo spin echo. T2W T2 weighed. WB whole brain. FL 2D flair 2D. BG: basal ganglia. 3 DF 3D flash. FOV field of view.
MPRAGE magnetization prepared rapid acquisition gradient echo.
BIBLIOGRAPHY
APPLICATIONS
Stereotactic surgery is widely applied for morphological
and functional procedures in the brain. Functional and
morphologic stereotaxis can be subdivided into diagnostic
and therapeutic procedures. A brief summary of these
applications is presented in Tables 1 and 2.
FUTURE DIRECTIONS
Advances in imaging techniques are characterized by faster acquisition sequences, more precise definition of eloquent structures, and minimization of artifacts. It is
feasible to predict a more sophisticated integration among
imaging, virtual reality computer, and robotics in a near
future. Possibly new surgical tools as thermal ablation,
cryoablation, and chemoablation will become routine, not
only for the brain, but for the whole body. The MRI would
also be able to provide sensitive monitoring of temperature
changes and tissue injury with high temporal resolution.
This would be an advantage once minimal injury inside or
surrounding an eloquent area may lead to a major deficit
(79), obviating the need of large surgical access to remove
tumors.
The increasing amount of publications (57,8086) discussing preliminary results using interventional MRI technique, exploring types of biomaterials (76,8792), and new
sequences of image acquisition (31,70) clearly show that
interventional MRI is in its early stages of development.
Whether frameless procedures under intraoperative MRI
guidance will replace frame stereotaxis in the future is still
an open question. Studies already claim that the same
accuracy obtained with framed technique is achieved
(33,40,41,87).
Frameless stereotactic concepts of registration of
images to patients anatomy will continue to be the basis
of surgical guidance, even with real-time imaging. Technological advances as interventional MRI carry issues like
high costs. Nevertheless, due to its minimally invasive
nature compared with other open surgical approaches,
1. Bakay RA et al. Delayed stereotactic transplantation technique in non-human primates. Prog Brain Res 1988;78:463
471.
2. Marino RJ, Gonzales-PortilloM. Preconquest Peruvian neurosurgeons: a study of Inca and pre-Columbian trephination
and the art of medicine in ancient Peru. Neurosurgery
2000;47:940950.
3. DN Z. Lence phalome`tre. Rev Gen Clin Ther 1980;19:302.
4. Lichterman BL. Roots and routes of Russian neurosurgery
(from surgical neurology towards neurological surgery).
J Hist Neurosci 1998;7:125135.
5. RD. Discours de la Methode. Paris: Vrin; 1992.
6. Clarke RH, Horsley V. On a method of investigating the deep
ganglia and tracts of the central nervous system (cerebellum).
Br Med J 1906;17991802:17991800.
7. Horsley VC R. The structure and functions of the cerebellum
examined by a new method. Brain 1908;31:45124.
8. Olivier A, Bertrand G, Picard C. Discovery of the first human
stereotactic instrument. Appl Neurophysiol 1983;46:8491.
9. Picard C, Olivier A, Bertrand G. The first human stereotaxic
apparatus. The contribution of Aubrey Mussen to the field of
stereotaxis. J Neurosurg 1983;59:673676.
10. De Salles AA. Stereotactic applications. In: De Salles AA,
Goetsch S. editors. Stereotactic Surgery and Radiosurgery.
Madison (WI): Medical Physics Publishing; 1993.
11. Moniz E. Lence phalographie arterielle, son importance dans
la localisation des tumeurs cerebrales. Rev Neurol 1927;2:72
90.
12. Dandy WE. Localization of brain tumors by cerebral pneumography.Am J Roentgenol 1923;10:610612.
13. Dandy WE. Ventriculography following the injection of air
into the cerebral ventricles. Ann Surg 1918;68:511.
14. Spiegel EA WH, Marks M, Lee ASJ. Stereotactic apparatus
for operations of the human brain. Science 1947;106:349
350.
15. Spiegel EA WH, Baird HW. Studies in stereoencephalotomy.I. Topical relationships of subcortical structures to the
posterior comissure. Confin Neurolog 1952;12:9133.
16. Benabid AL, et al. Chronic electrical stimulation of the
ventralis intermedius nucleus of the thalamus as a treatment
of movement disorders. J Neurosurg 1996;84:203214.
17. R. M. Surgical interruption of the pallidofugal fibers: its effect
on the syndrome of paralysis agitans and technical considerations in its application. NY State J Med 1942;42:317325.
272
STEREOTACTIC SURGERY
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
273
82. Hall WA, et al. Brain biopsy using high-field strength interventional magnetic resonance imaging. Neurosurgery
1999;44:807813. discussion 813804.
83. Bradford R, Thomas DG, Bydder GM. MRI-directed stereotactic biopsy of cerebral lesions. Acta Neurochir. (Suppl).
(Wien) 1987;39:2527.
84. Dorward NL, Paleologos TS, Alberti O, Thomas DG. The
advantages of frameless stereotactic biopsy over frame-based
biopsy. Br J Neurosurg 2002;16:110118.
85. Fahlbusch R, Ganslandt O, Nimsky C. Intraoperative imaging with open magnetic resonance imaging and neuronavigation. Childs Nerv Syst 2000;16:829831.
86. Moriarty TM, et al. Frameless stereotactic neurosurgery
using intraoperative magnetic resonance imaging: stereotactic brain biopsy. Neurosurgery 2000;47:11381145. discussion 11451136.
87. Koyama T, Handa J. Porous hydroxyapatite ceramics
for use in neurosurgical practice. Surg Neurol 1986;25:71
73.
88. Nitatori T, Hanaoka H, Hachiya J, Yokoyama K. MRI artifacts of metallic stents derived from imaging sequencing and
the ferromagnetic nature of materials. Radiat Med
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89. Port JD, Pomper MG. Quantification and minimization of
magnetic susceptibility artifacts on GRE images. J Comput
Assist Tomogr 2000;24:958964.
90. Shellock FG, Shellock VJ. Ceramic surgical instruments:
Ex vivo evaluation of compatibility with MR imaging at 1.5
T. J Magn Reson Imaging 1996;6:954956.
91. Shellock FG, Shellock VJ. Spetzler titanium aneurysm
clips: compatibility at MR imaging. Radiology 1998;206:
838841.
92. Tominaga T, et al. Magnetic resonance imaging of titanium
anterior cervical spine plating systems. Neurosurgery 1995;
36:951955.
93. Dorward NL, et al. Accuracy of true frameless stereotaxy:
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See also HYPERTHERMIA,
TISSUE ABLATION.
INTRODUCTION
Biologic materials such as collagen, tissue grafts, and
extracellular matrix (ECM) derived scaffolds are used
for tissue and organ repair and are typically regulated
as devices by the U.S. Food and Drug Administration
(FDA). As such, these materials must be properly processed and sterilized prior to clinical use. Sterilization of
biologic materials involves unique considerations (e.g., the
274
Sterilization Method
Heat Sterilization
Steam Sterilization
Ethylene Oxide
Radiation
Others
a
Standard(s)
ISO 20857
ISO 11134, ISO/DIS 17665-1,
ISO/DIS 17665-2
ISO/DIS 11135-1, ISO/DIS 11135-2,
ISO 10993-7 (Residuals)
ISO/DIS 11137-1, ISO/DIS 11137-2,
ISO/DIS 11137-3
ISO 10993 (1-18), ASTM E1766-95,
F2347-03, F2103-1, F2064-00
3
2
log10 (CFU/unit)
SAL of 103
1
0
1
SAL of 106
2
3
4
5
6
0
10
20
30
40
50
60
Time (min)
Figure 1. Example of data obtained from a fractional sterilization
run to determine the time required to achieve the desired SAL at a
fixed temperature. Note: The data may not have a linear form and
will depend on the microbial load and the type of microbes present.
(338 8F)
(320 8F)
(302 8F)
(284 8F)
(250 8F)
Sterilization Time
60 min (1 h)
120 min (2 h)
150 min (2.5 h)
180 min (3 h)
Overnight
275
276
Ethylene oxide
Functional group
O
Product
R
OH
R
O
OH
Figure 2. Examples of possible reaction between ETO and common functional groups in
biological molecules (16,17). For a more complete explanation of the reactions please refer
to (16,19).
NH2
SH
OH
OH
NH
OH
S
OH
O
HO
CH2
oxirane
Ethylene oxide
H2C
OH
CH2
ethane-1,2-diol
Ethylene glycol
Cl
H2C
277
OH
CH2
2-chloroethanol
Ethylene chlorohydrin
Figure 3. Structure of ETO and its byproducts: Ethylene glycol (ETG) and ethylene chlorohydrin (ETC). The
ETO is flammable and highly explosive and has been
associated with potential mutagenic, teratogenic, or
carcinogenic properties. Both ETG and ETC are toxic
as well (18).
ray
High-energy
state
Low-energy
state
Protective
cover
Source
Decrease dose
Material or
device being
sterilized
Figure 4. Schematic representation of a gamma source and how
devices are typically sterilized. Dosage may be adjusted by calibrating the distance between the source and the device. Other
forms may be employed depending on the facilities and the
intended application.
278
e-Beam Irradiation
Mechanism of Action. e-Beam irradiation involves the
generation of a beam of electrons from a linear accelerator.
The beam of electrons can be manipulated to achieve the
desired dose by varying power and the exposure time. The
sterilizing effect of e-beam irradiation on polymeric materials is similar to that described for gamma irradiation
except for less penetrability of the beam into target materials. The main effect of e-beam irradiation comes from the
ionizing electrons that result in the destruction of nucleic
acids and proteins required for cellular processes. One
primary difference between gamma radiation and e-beam
is that the electron beam can be focused on the target
Table 3. Example of Currently Marketed Biologic Devices and the Form of Terminal Sterilization Employed
Product
TM
CuffPatch
PelvicolTM
Bard1 Dermal Gllograft
FasLata1 Allograft
OaSis1
Stratasis1
Surgisis1
RestoreTM
TissueMend1
PermacolTM
Tutopatch1
Tutoplast1
Company
Source
Sterilization
Arthrotech, Inc.
Bard, Inc.
Bard, Inc.
Bard, Inc.
Cook Biotech, Inc.
Cook Bioetch, Inc.
Cook Biotech, Inc.
Depuy Orthopedics, Inc.
TEI Bioscience, Inc.
Tissue Science Laboratories, Inc.
Tutogen Medical, Inc.
Tutogen Medical, Inc.
Gamma
Gamma
Gamma
Gamma
ETO
ETO
ETO
Gamma
ETO
Gamma
Gamma
Gamma
279
Table 4. Summary of the Most Commonly Used Sterilization Methods and Their Advantages, Disadvantages, and Typical
Doses as Discussed in this Article
Sterilization Method
Advantages
Disadvantages
Typical Dose
Dry heat
Moist heat
Ethylene oxide
Ionizing radiation
high intensity light, ultraviolet light, vapor systems (combination of hydrogen peroxide and peracetic acid), exposure to chlorine dioxide, and filtration methods (510 k
Sterility Review Guidance K90-1). In addition, low temperature gas plasma and machine-generated X rays can be
used for sterilization purposes.
Chemicals are often used to reduce the bioburden, disinfect, and sterilize biologic materials. Table 5 lists a few of
the most commonly used chemicals for the disinfection and/
or sterilization of grafts and naturally occurring biomaterials. Glutaraldehyde is currently used to sterilize and
remove the antigenicity of many porcine-derived products
(e.g., heart valves and pericardium). Formaldehyde and a
combination of formaldehyde and low temperature steam
Table 5. Common Chemical Sterilants and Disinfectants Used for Biologic Materials
Chemical
Uses
O
Glutaraldehyde
O
HO
O
Peracetic acid
HO
OH
Hydrogen peroxide
HO
Ethanol
References
(1,3639)
(1,36,4047)
(1,23,4852)
(1,36,39,45,5355)
Table 6. Example of the Disinfection Process Used to Reduce the Bioburden of Naturally Occurring Biomaterialsa
Step
Solution
Time
0.1% (v/v) peracetic acid 4% (v/v) ethanol, and 95.9% (v/v) sterile water
Sterile 1X PBS pH 7.4
Sterile water
2h
30 min
30 min
280
n
O
Glutaraldehyde
Gluteraldehyde polymer
GLOSSARY
O
O
n
N
Allograft
Bioburden
Disinfection
Endotoxins
Protein
Protein
O
Protein
A
+
N
+
Protein
A
O
O
SUMMARY
There are several options for the sterilization of biologic
materials and each option has its advantages and disadvantages. The majority of biologic materials classified as
medical devices are sterilized by either gamma or e-beam
Extracellular
matrix
(ECM)
Inactivation
Medical
device
Pyrogens
Spore
Xenograft
BIBLIOGRPHY
1. Block SS. Disinfection, Sterilization, and Preservation. 5th
ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2001.
p 1481.
2. Ratner BD. Biomaterials science: An introduction to materials in medicine. 2nd ed. 1996, San Diego: Academic Press;
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3. Baird RM, Hodges NA, Denyer SP. Handbook of Microbial
Quality Control. Pharmaceuticals and Medical Devices.
New York: Taylor & Francis; 2000.
4. Halls NA. Achieving Sterility in Medical and Pharmaceutical
Products. Vol. 64. New York: Marcel Dekker, Inc.;
1994.
5. Perkins JJ. Principles and Methods of Sterilization in
Health Sciences. 2nd ed. Springfield (IL): Thomas; 1969.
p 560.
6. Pruss A, et al. Comparison of the efficacy of virus inactivation
methods in allogeneic avital bone tissue transplants. Cell
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7. Bronzino JD. The Biomedical Engineering Handbook. Boca
Raton (FL): CRC Press: IEEE Press; 1995. p 591.
8. Chen SS, Humphrey JD. Heat-induced changes in the
mechanics of a collagenous tissue: Pseudoelastic behavior
at 37 degrees C. J Biomech 1998;31(3):211216.
9. Jun JH, et al. Effect of thermal damage and biaxial loading on
the optical properties of a collagenous tissue. J Biomech Eng
2003;125(4):540548.
10. Harris JL, Humphrey JD. Kinetics of thermal damage to a
collagenous membrane under biaxial isotonic loading. IEEE
Trans Biomed Eng 2004;51(2):371379.
11. Mazzu AL, Smith CP. Determination of extractable methylene dianiline in thermoplastic polyurethanes by HPLC.
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extracts from synthetic polymers used in medicine. Arch
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13. Berger K, Sauvage LR. Late fiber deterioration in Dacron
arterial grafts. Ann Surg 1981;193(4):477491.
14. Speirs AD, et al. Biomechanical properties of sterilized
human auditory ossicles. J Biomech 1999;32(5):485
491.
15. Prolo DJ, Pedrotti PW, White DH. Ethylene oxide sterilization of bone, dura mater, and fascia lata.for human transplantation. Neurosurgery 1980;6(5):529539.
16. Fraenkel-Conrat H. The action of 1,2-epoxides on proteins.
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41.
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43.
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45.
46.
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48.
49.
50.
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52.
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55.
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STRAIN GAGES
degradation characteristics of an epoxy-fixed biological tissue. J Biomed Mater Res 1997;37(3):376383.
Mucke H, Wenzel KP. [Preparation of heart valves for grafting after sterilization with peracetic acid]. Z Exp Chir
1973;6(4):252255.
Sprossig M, et al. [Sterilization of heart valve transplants
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362.
Wutzler P, et al. [Combined cleaning and cold sterilization
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Z Med Labortech 1975;16(5):253259.
Wenzel KP. [Final sterilization of formaldehyde-preserved
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Lomas RJ, et al. Assessment of the biological properties
of human split skin allografts disinfected with peracetic
acid and preserved in glycerol. Burns 2003;29(6):515
525.
Pruss A, et al. Peracetic acid-ethanol treatment of allogeneic
avital bone tissue transplantsa reliable sterilization
method. Ann Transplant 2003;8(2):3442.
Huang Q, et al. Use of peracetic acid to sterilize human
donor skin for production of acellular dermal matrices
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287.
Lomas RJ, et al. Effects of a peracetic acid disinfection
protocol on the biocompatibility and biomechanical properties of human patellar tendon allografts. Cell Tissue Bank
2004; 5(3):149160.
Glowacki J. A review of osteoinductive testing methods and
sterilization processes for demineralized bone. Cell Tissue
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Brown SA, et al. Effects of different disinfection and sterilization methods on tensile strength of materials used for
single-use devices. Biomed Instrum Technol 2002;36(1):23
27.
Lambert RJ, Johnston MD, Simons EA. A kinetic study of the
effect of hydrogen peroxide and peracetic acid against
Staphylococcus aureus and Pseudomonas aeruginosa
using the bioscreen disinfection method. J Appl Microbiol
1999;87(5):782786.
Rutala WA. Disinfection and sterilization of patientcare items. Infect Control Hosp Epidemiol 1996;17(6):377
384.
Rutala WA, Weber DJ. Disinfection of endoscopes: review of
new chemical sterilants used for high-level disinfection.
Infect Control Hosp Epidemiol 1999;20(1):6976.
Pruss A, et al. Validation of the sterilization procedure of
allogeneic avital bone transplants using peracetic acidethanol. Biologicals 2001;29(2):5966.
Hodde J, Hiles M. Virus safety of a porcine-derived medical
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Bioeng 2002;79(2):211216.
Scheffler SU, et al. Biomechanical comparison of human
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115.
Freytes DO, et al. Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials 2004;25(12):2353
2361.
STRAIN GAGES
PAUL C. DECHOW
QIAN WANG
A & M University Health
Science Center
Dallas, Texas
INTRODUCTION
Strain gages are devices that allow measurement of the
change in the dimensions, displacement, or deformation of
an object. These devices have been used extensively in a
wide variety of engineering applications over the past
century and, in recent decades, their use in biomedical
applications, such as in the production of transducers for
biomedical monitoring and research, has increased tremendously. These transducers measure a variety of parameters, including strain, displacement, pressure,
acceleration, force, and temperature. The chief types of
strain gages are mechanical, optical, acoustical, and electrical. There are several types of electrical gages including
capacitance, inductance, semiconductor, and resistance
strain gages. The electrical resistance strain gages are
the most widely used types of gages in engineering and
biomedical applications today and receive the most extensive treatment in this article. Before discussing the various
types of strain gages in more detail, it is useful to have a
working understating of what strain and stress are and
their relationship to each other.
STRAIN AND STRESS
Strain is a dimensionless unit, which is defined as the ratio
of the change in unit length over the original length,
e DL=L
(1)
STRAIN GAGES
(2)
283
284
STRAIN GAGES
transducers, and other applications requiring measurement of very small strains. These gages provide a large
signal output relative to strain, as indicated by their large
gage factors (GF for a definition see below), which can be as
high as 200. By contrast, GFs for electrical resistance
strain gage are usually two or less. Unfortunately, semiconductor strain gages also suffer from an extreme sensitivity to temperature. In addition, the piezoresistive effect
varies with strain giving these gages ranges of nonlinearity. Semiconductor gages are typically constructed from
silicon or germanium. Because of the high receptivity of
these materials, the gages consist of a small filament of a
single crystal of the semiconductor material mounted on
some type of carrier. The receptivity and strain-measuring
properties of the crystal can be varied by altering the
amount of impurities in the crystal. The fatigue life of
semiconductor gages for cyclic strains is less than that of
electrical resistance-type gages. These gages are then
commonly employed in fields with low strains where frequent loading does not lead to gage failure.
Electrical Strain Gages: Resistance Type
The electrical resistance strain gages are the most widely
used gages in engineering and biomedical fields (Fig. 1).
The principles behind these gages were first discovered by
Lord Kelvin in 1856 when he noted (1) that the resistance of
a metal wire increases with increasing strain and
decreases with decreasing strain and (2) that different
materials have different sensitivities to strain.
Electrical resistance strain gages are also sensitive to
temperature changes, but not to the extent of semiconductor gages. Most gages have a several hundred degree range
under which they function best. However, within that
range, temperatures must be monitored carefully in
order to compensate for apparent strain caused by shifts
in temperature. However, gages are available that
have self-temperature compensation. In these gages, the
0 90 T Rosette
0 45 90 Rectangular Rosette
(3)
STRAIN GAGES
cardiovascular and respiratory dimensional and plethysmographic (volume-measuring) determinations. The gages
are made of a narrow silicone-rubber tubes, usually with an
inside diameter of 0.5 mm, and they range in length from
3 to 25 cm. The gages are filled with mercury or with an
electrolyte or conductive paste and the ends are sealed with
copper, silver, or platinum electrodes. When the gage is
stretched, the diameter of the tube decreases and the
length increases, increasing the resistance. These gages
allow measurement of large-dimensional changes. They
are accurate in the 10,000100,000 me range. Strains as
high as 300,000 me (30%) can be measured with distortion
as small as 4%.
R4
R1
+
Ei
285
Eo
R2
R3
Figure 3. Diagram for a Wheatstone bridge circuit (3). Abbreviation: R3 and R4-resistors, others as in Fig. 2.
R1
Ei
R2
Eo
286
STRAIN GAGES
R1
Ei
Current loop
R4
Rw1
RA
+
_
R2
R3
RB
_
+
RA
RB
Rw3
Gage
I,
electric
current
source
+
Eo
_
R
Vg
Rw4
Vout
Rw2
Rref,
reference
reslstance
2.
3.
4.
5.
6.
7.
Amplifiers
There are several good amplifiers and signal conditioners
available commercially for use with strain gages (see
Further Reading for some sources of information on specific
amplifiers). An example for a simple differential amplifier
circuit for use with a Wheatstone bridge is illustrated in
Fig. 5, where the output voltage (Eo) is amplified by the
including of sensors RA and RB. In general, the better
amplifiers should have a variety of features including some
of the following:
1. The ability to complete a variety of Wheatstone
bridge circuits ranging up to a full bridge configuration with all resistors in the bridge replaced by
strain gages. Dummy gages for a less than a full
Vref
APPLICATIONS
Strain gages have enabled significant advances in many
biological and biomedical fields. They have been used
extensively in a wide variety of biomedical and clinical
applications, chiefly to measure strain, stress, pressure,
force, or displacement in or produced by living structures,
or in vitro simulations. It is the aim of the following section
to document several of these applications in order to give
the reader a practical knowledge of the possibilities for
using strain gages in basic biological and biomechanical
research as well as in clinical sciences and medical
diagnosis.
STRAIN GAGES
287
288
STRAIN GAGES
2.5 10.0
3.8
37.5
17.5
R1
15.0
R2
inter ior
9.4
R3
R4
STRAIN GAGES
BIBLIOGRAPHY
1. Dechow PC. Strain gage. In: Webster JG, editor. Encyclopedia of Medical Devices and Instrumentation. New York:
Wiley; 1988. p 27152721.
2. Shull LC. Basic circuits. In: Hannah RL, Reed SE, editors. Strain Gage Users Handbook. London: Elsevier;
1992. p 79132.
3. Dorsey J. Semiconductor strain gages. In: Hannah RL, Reed
SE, editors. Strain Gage Users Handbook. London: Elsevier;
1992. p 365448.
4. Chadwick EK, Nicol AC, Floyd S, Gray TG. A telemetry-based
device to determine the force-displacement behaviour of
materials in high impact loading situations. J Biomech
2000; 33:361365.
5. Schatzker J, Sumner-Smith G, Hoare J, McBroom R. A
telemetric system for the strain gauge determination of strain
in bone in vivo. Arch Orthop Trauma Surg 1980;96:309311.
6. Anderson KF. The Anderson Loop: NASAs successor to the
Wheatstone bridge. ISA Transactions 1997;36:351356.
7. Wolff J. Das Gesetz der transformation der knochen. Berlin;
1892.
8. Gurdjian ES, Lissner HR. Mechanism of head injury as
studied by the cathode ray oscilloscope. Preliminary report.
J Neurosurg 1944;1:393399.
9. Evans FG. Methods of studying the biomechanical significance of bone form. Am J Phys Anthropol 1953;11:413436.
10. Endo B. Experimental studies on the mechanical significance
of the form of the human facial skeleton. J Fac Sci Univ Tokyo
Sect 5 1966;3:(Pt I).
11. Cochron GVB. A method for direct recording of electromechanical data from skeletal bone in living animals. J Biomech
1974;7:563565.
12. Wright TM, Hayes WC. Strain gage application on compact
bone. J Biomech 1979;12:471475.
13. Hylander WL, Bays R. An in vivo strain-gauge analysis of the
squamosal-dentary joint reaction force during mastication
and incisal biting in Macaca mulatta and Macaca fascicularis. Arch Oral Biol 1979;24:689697.
14. Hylander WL. In vivo bone strain in the mandible of
Galago crassicaudatus. Am J Phys Anthropol 1977;46:309326.
15. Ross CF. In vivo function of the craniofacial haft: The interorbital pillar. Am J Phys Anthropol 2001;116:108139.
16. Daegling DJ, Hylander WL. Biomechanics of torsion in the
human mandible. Am J Phys Anthropol 1998;105:7387.
17. Behrents RG, Carlson DS, Abdelnour T. In vivo analysis of
bone strain about the sagittal suture in macaca mulatta
during masticatory movements. J Dent Res 1978;57:904908.
18. Herring SW, Rafferty KL. Cranial and facial sutures: functional loading in relation to growth and morphology. In:
Davidovitch Z, Mah J, editors. Biological Mechanisms of Tooth
Eruption, Resorption and Replacement by Implants. Boston:
Harvard Society for Advanced Orthodontics; 2000. p 269276.
19. Ahmad F, et al. Strain gauge biomechanical evaluation of
forces in orbital floor fractures. Br J Plast Surg 2003;56:39.
20. Ekenman I, et al. Local bone deformation at two predominant
sites for stress fractures of the tibia: an in vivo study. Foot
Ankle Int 1998;19:479484.
21. Unnewehr M, et al. Fracture properties of the human mandible. Int J Legal Med 2003;117:326330.
22. Lanyon LE. Analysis of surface bone strain in calcaneus of
sheep during normal locomotionstrain analysis of calcaneus. J Biomech 1973;6:4149.
23. Lanyon LE, Magee PT, Baggott DG. Relationship of functional stress and strain to the processes of bone remodeling
experimental-study on the sheep radius. J Biomech
1979;12:593600.
289
290
STRAIN GAGES
46. Brosnan RJ, et al. Effects of ventilation and isoflurane endtidal concentration on intracranial and cerebral perfusion
pressures in horses. Am J Vet Res 2003;64:2125.
47. Cooperman M, et al. Detection of deep venous thrombosis by
impedance plethysmography. Am J Surg 1979;137:252254.
48. Maskell NA, et al. The use of automated strain gauge plethysmography in the diagnosis of deep vein thrombosis. Br J
Radiol 2002;75:648665.
49. Andres PL. et al. Quantitative assessment of neuromuscular
deficit in ALS. Neurol Clin 1987;5:125141.
50. de V Cotton M. Circulartory changes affecting measurement
of heart force in situ with strain gage arches. Am J Physiol
1953;174:365370.
51. Mote PS, Pruett JK, Gramling ZW. Effects of halothane and
enflurane on right ventricular performance in hearts of dogs
anesthetized with pentobarbital sodium. Anesthesiology
1983;58:5360.
52. Sarel O, Hasin Y, Rogel S. Myocardial conduction time and
antiarrhythmic drugs. J Electrocardiol 1981;14:261266.
53. Hasin Y, Sarel O, Rogel S. Electrical and mechanical
response in biventricular mechanical alternans. Arch Int
Physiol Biochim 1979;87:1928.
54. Cavallo SA, Baken RJ. Prephonatory laryngeal and chest
wall dynamics. J Speech Hearing Res 1985;28:7987.
55. Souhrada JF, Dickey DW. Mechanical activities of trachea as
measured in vitro and in vivo. Respir Physiol 1976;26:2740.
56. Flack FC, James ED. Case study using simultaneous bladder
pressure and urine loss measurements. Urol Int 1975; 30:103108.
57. Johnson CP, et al. Effects of intestinal transplantation on
postprandial motility and regulation of intestinal transit.
Surgery 2001;129:614.
58. Pascaud XB, Genton MJ, Bass P. A miniature transducer for
recording intestinal motility in unrestrained chronic rats. Am
J Physiol 1978;235:E532538.
59. Ueda S, Wada A, Umemura S. Methodological validity and feasibility of the nitric oxide clamp technique for nitric oxide research in
human resistant vessels. Hypertens Res 2001;27:351357.
60. Bigelow N, et al. A preliminary report on a study of a
correlation between emotional reactions and peripheral blood
circulation, using a strain gauge plethysmograph. Psychiatr
Q 1955;29:193202.
61. Forgione AG, Barber TX. A strain gauge pain stimulator.
Psychophysiology 1971;8:102106.
62. Coakley D, Williams R, Morris J. Minute eye movement during
sleep. Electroencephalogr Clin Neurophysiol 1979;47:126131.
63. Mamelak A, Hobson JA. Nightcap: A home-based sleep monitoring system. Sleep 1989;12:157166.
64. Miyazaki S, et al. Using an air-pad sensor for the diagnosis of
sleep apnea: A trial study. Psychiat Clin Neurosci 2002;56:
315316.
65. Janssen E, Vissenberg M, Visser S, Everaerd W. An in vivo
comparison of two circumferential penile strain gauges: The
introduction of a new calibration method. Psychophysiology
1997;34:71720.
66. Kiely ME, Thavundayil JX, Lal S. Effect of blood sampling on
apomorphine-induced penile tumescence in erectile impotence:
A case report. J Psychiat Neurosci 1995;20:233235.
67. Hahn PM, Leder R. Quantification of penile buckling force.
Sleep 1980;3:9597.
68. An KN, Chao EY, Askew LJ. Hand strength measurement
instruments. Arch Phys Med Rehabil 1980;61:366368.
69. Burnham RS, Bell G, Olenik L, Reid DC. Shoulder abduction
strength measurement in football players: Reliability and
validity of two field tests. Clin J Sport Med 1995;5:9094.
70. Henning CE, Lynch MA, Glick Jr KR. An in vivo strain gage
study of elongation of the anterior cruciate ligament. Am J
Sports Med 1985;13:2226.
Further Reading
These books contain much useful information on strain gages,
stress and strain analysis, and instrumentation for strain gages.
Internet searches using strain gage or strain gauge as key words
also yield a wide variety of information about bridges, strain gages, associated products, and instrumentations, manufacturers,
technique supports, and training sessions.
Dally JW, Riley WF. Experimental Stress Analysis. 3rd ed.
New York: McGraw-Hill; 1991.
Hannah RL, Reed SE, editors. Strain Gage Users Handbook.
London: Elsevier; 1992.
Khan AS, Wang X. Strain Measurements and Stress Analysis.
Upper Saddle River (NJ): Prentice Hall; 2000.
Kost GJ, editor. Handbook of Clinical Automation, Robotics, and
Optimization. New York: Wiley; 1996.
Perez R. Design of Medical Electronic Devices. London: Academic
Press; 2002.
Prutchi D, Norris M. Design and Development of Medical Electronic Instrumentation: A Practical Perspective of the Design,
Construction, and Test of Medical Devices. Hoboken, NJ:
Wiley-Interscience; 2004.
Webster JG, editor. Medical Instrumentation: Application and
Design. 3rd ed. New York: Wiley; 1998.
Window AL. Strain Gauge Technology. 2nd ed. Burlington (MA):
Elsevier Science; 1992.
Ballantyne GH, Marescaux J, Giulianotti PC, Primer of Robotic &
Telerobotic Surgery. Hagerstown MD: Lippincott Williams &
Wilkins; 2004.
See also BIOMATERIALS,
STRESS TESTING.
SYSTEMIC HYPERTHERMIA.
SYSTEMIC
See HYPERTHERMIA,
T
TACTILE STIMULATION
municate information about a manipulated objects compliance, viscosity, mass, size, and gross shape. Researchers
have made less progress toward communicating tactile
information such as surface texture, fine shape, roughness,
slip, vibration or temperature. These later object properties
could potentially be important in helping the user distinguish between morphologically similar objects or, in the
case of surgical or medical imaging applications, to assess
tissue type or of the degree and extent of tissue damage
(2,3). Indeed, in cases where visual information is not
available, tactile information may form a users only basis
for decision making.
Other applications for tactile stimulation include sensory substitution or augmentation systems such as those
for the blind or deaf. For example, using a computer poses a
particular challenge for the visually impaired. Textual
information can be read aloud by the computer, but as
graphical computer interfaces become more and more ubiquitous, the blind user is placed at a greater disadvantage.
One solution is to represent the graphical information
through a tactile display. Further applications are discussed below in the section on stimulation techniques.
CHRISTOPHER J. POLETTO
National Institutes of Health
INTRODUCTION
Definitions
In the most general terms, tactile stimulation is the deliberate elicitation of any of a range of sensations perceived
through the sense of touch. The stimulation can be delivered by any means and to any part of the body where touch
can be felt. Most commonly, tactile stimulation is applied to
the skin, usually to the fingertips, abdomen, or forearms,
but tactile stimulation is also used on the tongue as a
possible communications tool and at the back of the throat
during therapy in people with dysphagia. Clinically relevant tactile stimulation can be as simple as a caregiver
stroking a baby to encourage healthy development or
involve of thousands of sophisticated actuators in arrays
working in concert to present a virtual tactile environment.
Tactile perception should be distinguished from kinesthetic and haptic perception. Tactile perceptions include
temperature, skin curvature and stretch, vibration, slip,
pressure and local contact force. Kinesthesia is the perception of the relative position and movement of our body parts
(proprioception), as well as the sensation of muscular effort
exerted while touching or manipulating objects. Although
M. Dessoir (1892) originally defined haptic (haptik in German, modified from the Greek word haptikos) to mean the
study of touch and tactile sensations, especially as a means
of communication (Oxford English Dictionary), the term
haptic is applied much more broadly now. Haptic perceptions combine tactile and kinesthetic perceptions to provide
a sense of environmental or object properties such as shape
(1). Many devices referred to as tactile displays, especially those intended for virtual reality or telepresence
applications, actually combine tactile and kinesthetic feedback, but this article is concerned only with devices that
deliver tactile stimulation. The focus will be on the
mechanical (vibrotactile and shape displays) and electrical
(electrotactile) stimulators that elicit sensations of vibration, pressure, and local contact force, because these types
of stimulators are most often used in current tactile stimulation applications.
TACTILE PHYSIOLOGY
Understanding how tactile stimulation techniques function requires a basic understanding of the physiological
mechanisms that mediate our sense of touch. When we
touch an object, the distribution of contact forces deforms
our skin. The temporal and spatial distribution of the
deformation determines which mechanoreceptive nerve
terminals are excited. Each mechanoreceptive nerve fiber
terminates as one or more dendrites. The dendrites have
stretch-gated ion channels that allow ions to flow and
depolarize the dendrite when their membranes are
stretched or deformed. If the depolarization is sufficient,
nearby voltage gated channels initiate an action potential
that travels up the nerve to the central nervous system.
The particular way that the deformation of the skin leads to
bending or stretching of the dendrites varies from one type
of mechanoreceptor to another and is due to the structure
of the sensory receptor at the end of the fiber. The firing
frequencies of the mechanoreceptive nerve fibers are then
decoded by the central nervous system to ultimately give
rise to our sense of touch.
The skin is made up of three distinct layers: the epidermis, dermis, and subcutaneous fat. Made up of primarily keratinocytes, the epidermis is the outermost layer and
serves as a protective interface with the outside world. The
outermost portion of the epidermis is the stratum corneum,
which is made up of dead, flat cells that shed and are
replenished about every 2 weeks. The epidermis does not
contain any blood vessels and is dependant on the deeper
skin layers for its oxygen and nutrients. A very
thin membrane, the basement membrane, attaches the
Applications
Telepresence and telerobotic technologies are emerging as
important fields with great potential for use in biomedical
applications such as the control of surgical robots. These
applications require mechanisms for the feedback of information to the human operator from a set of remote sensors.
This feedback has been visual and auditory in nature, but
developing technologies are permitting the use of certain
forms of haptic feedback such as force reflection to com291
292
TACTILE STIMULATION
ADAPTATION
RECEPTIVE FIELDS
Small, sharp borders
Large, obscure borders
RA I
RA II
SA I
Slow,
static
response
present
SA II
Fast,
no static
response
Figure 1. Mechanoreceptors in skin. Mechanoreceptive innervation of human hairless (glabrous) skin. (Diagram provided by
Kenneth Johnson.)
TACTILE STIMULATION
293
294
TACTILE STIMULATION
Figure 3. Vibrotactile versus shape displays. Vibrotactile displays (a) use pins that vibrate around a common set point. Larger
oscillations are used to produce sensations of higher intensity (top
inset). Shape, or static, displays (b) present more naturalistic
surface contours and use larger indentations to encode regions
of higher intensity.
TACTILE STIMULATION
295
296
TACTILE STIMULATION
TACTILE STIMULATION
297
electrodes and could limit the desirability of using electrotactile displays. One way to increase the dynamic range
would be to inactivate the pain fibers by applying a long
depolarizing prepulse (DPP) prior to the stimulus pulse
(the DPP would only be introduced significantly above
sensation threshold, to prevent the concurrent elevation
of both thresholds). This approach has been shown to
significantly increase the pain thresholds, thereby increasing the dynamic range (83).
Despite the difficulties associated with fingertip electrotactile displays using small electrodes, some groups have
been successful using electrotactile stimulation to present
simple patterns to the fingertips. Kaczmarek et al. (81)
developed a 49-point fingertip-scanned electrotactile display that consists of 0.89 mm diameter, flat-topped stainless steel electrode pins, each surrounded by a 2.36 mm
diameter air gap insulator arranged in a square 7 7 array
100
Touch % local
80
60
40
20
0
1 mm
2 mm
4 mm
8 mm
Electrode diameter
Figure 4. Qualitative results graphs. Electrotactile stimulation
can produce sensations that are local or distal to the electrode. The
graph shows the percentage of touch sensations that were felt local
to (as opposed to distal to) the stimulating electrode, calculated as
the percentage of all trials (summed across subject, session, pulse
width and repetition, 271288 total trials per bar) that the subject
reported as local. Bar color indicates stimulus polarity: black,
anodic; white, cathodic. Error bars indicate smallest and largest
95% confidence intervals. [Data taken from (83).]
298
TACTILE STIMULATION
Finger
Electrode
Pressure sensor
Object surface
Optical sensor
FUTURE DIRECTIONS
For most of its history, tactile stimulation has been developed and used primarily for sensory substitution or sensory
augmentation systems for persons with sensory impairment. Many of these projects have been generally successful in restoring function and greater autonomy to their
users, but target audiences have been small and large scale
corporate investment has not been forthcoming. Although
applications of tactile stimulation intended to help individuals with impairments are seen as important and will
likely continue, it is also likely that applications with mass
market appeal will drive the greater part of tactile stimulation technology development. Such applications are currently emerging in immersive virtual reality for
entertainment and training purposes, teleoperation and
telepresence for industry and medicine, and in personal
communications.
There appear to be two separate trends in the technical
progression of tactile displays. One trend is toward the
development of fingertip tactile interfaces with greater
sophistication and complexity for comfortably and portably
communicating large amounts of data, such as surface
texture. Such development will be important for applications where realistic surface perception is required, such as
teleoperation, telesurgery, and immersive virtual reality.
TACTILE STIMULATION
299
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446.
INTRODUCTION
Telemedicine and teleradiology have become increasingly
important as our countrys healthcare delivery system
gradually changes from fee-for-service to managed, capitated care. During the past several years, we have seen the
trend of primary care physicians joining health maintenance organizations (HMOs). These HMOs purchase smaller hospitals and form hospital groups under the umbrella
of HMOs. Also, academic institutions form consortia to
compete with other local hospitals and HMOs. This consolidation allows the elimination of duplication and the
streamlining of healthcare services among hospitals.
As a result, costs are reduced, but at the same time because
of the downsizing, the number of experts available for
service also decreases. Utilization of telemedicine and
TELERADIOLOGY
-Teleradiology-
DSO
Direct
digital
Digitizer:
vidicon,
laser
scanner
DSL
Images
Formatted
image data
DS3
ATM
internet 2
303
Telemanagement
almost real-time
Workstation
Radiological examinations
HIS/
RIS
Patient
related
information
Management
software
Telediagnosis,
4-24 h
Images and information
transmitted to the expert center
Fax/Phone
Teleconsultation,
1/2 h
Fax/Phone
Phone
line
Referring site
(a)
Expert center
Expert center
radiologists make the diagnosis
(b)
Most simplistic
Simplistic
Complicated
Most complicated
Historical Images/RIS
Archive
No
Yes
No
Yes
No
No
Yes
Yes
304
TELERADIOLOGY
HIS
database
Generic PACS
components & data flow
reports
Database
gateway
Imaging
modalities
Acquisition
gateway
PACS controller
& archive server
Application
servers
Workstations
Web server
Telerad
PACS
Image capture
Display technology
Networking
Storage
Compression
Digitizer
Same
WAN
Short
Yes
DICOM
Same
LAN
Long
May be
No. of Images/Exam
One Examination
128 128 12
256 256 12
512 512 8(24)
512 512 8
512 512 8
512 512 24
512 512 24
512 512 12
2048 2048 12
2048 2048 12
4000 5000 12
3060
603000
20240
1540
1
1
420
403000
2
2
4
12 MB
8 MB up
560 MB
410 MB
0.26 MB
0.79 MB
315 MB
20 MB up
16 MB
16 MB
160 MB
TELERADIOLOGY
Image Capture
In image capture, if the original image data are on film,
then either a video frame grabber or a laser film digitizer is
used to convert them to digital format. A video frame
grabber produces low quality digital images, but is faster
and cheaper. On the other hand, laser film digitizers
produce very high quality digital data, but take longer
and cost more compared to the video frame grabber. During
the past several years, direct Digital Imaging and Communication in Medicine (DICOM) standard output images
from CR, DR, CT, and MR have been used extensively in
teleradiology.
Data Reformatting
After images are captured, it is advantageous to convert
these images and related data to industry standards
because multiple vendors equipment can be used in the
teleradiology chain. The two common standards used in
medical imaging industry are the DICOM (6) for images
and Health Level 7 (HL7) (7) for textual data. The DICOM
standard includes both the image format as well as the
communication protocols based on the standard TCP/IP.
Health level 7 is the standard for textual data, it uses the
TCP/IP communication protocols.
Image Storage
At the expert center, a local storage device is used before
images are displayed. The capacity of this device can range
from several hundred megabytes to many gigabytes. A
long-term archive, such as a small DLT (digital linear tape)
library, is used for teleradiology applications that require
historical images and diagnostic reports, related patient
information, and current images and diagnosis.
Display Workstation
For an inexpensive teleradiology system, a low cost 512line single monitor can be used for displaying images.
However, high resolution multimonitor display workstations are needed for the primary diagnosis.
Table 4 shows the specifications of a 2000- and a 1600line workstation used for teleradiology primary readings.
These state-of-the-art technology diagnostic workstations,
use two monitors with over 2 GB of local storage, and can
display images and reports from the local storage in 12 s.
A 2000-line LCD monitor workstation costs from $20,000 to
30,000, and a 1,600 line costs from $15,000 to $20,000.
User-friendly image display software is necessary for easy
and convenient use by the radiologist at the workstation.
Table 4. Specifications of High-End 2000 and 1600 Line
Workstations for Teleradiology
Two LCD Monitors
12 week local storage for current previous exams
12 s display of images and reports from local storage
HL7 and DICOM conformance
Simple image processing functions
305
56 kbits/s
56 to (24 56) kbits/s
144 kbits/s 8 Mbits/s
1.5 Mbits/s
56 kbits/s to 1.5 Mbits/s
28 DS-1 45 Mbits/s
155 Mbits/s and up
100 Mbits/s and up
Communication Networks
An important component in teleradiology is communication networks used for the transmission of images and
related data from the acquisition site to the expert center
for diagnosis. Since most teleradiology applications are not
within the same hospital complex, but through interhealthcare facilities in metropolitan areas or at longer
distances, the communication technology involved requires
wide area network (WAN) technology. Wide area network
can be wireless or with cables. In wireless WAN, some
technologies available are microwave transmission and
communication satellites. Wireless WAN has not been used
extensively in teleradiology due to its higher cost. Table 5
shows cable technology available in WAN from the low
communication rate DS-0 with 56 kb/s, to DSL (Digital
Subscriber Line, 144 kb/s to 8 Mb/s, depending on data
traffic and the subscription), T-1 and T-3 lines starting
from 1.5 Mb/s, to very high broadband communication DS3 with 45 Mb/s (8). These WAN technologies are available
through either a long distance or local telephone carrier, or
both. The cost of using WAN is a function of transmission
speed and the distance between sites. Thus, within a fixed
distance, for a DS-0 line with low transmission rate, the
cost is fairly low compared to DS-3, which is much faster,
but very expensive. Most of the private lines, for example,
T-1 and T-3, are point-to-point and the cost depends on the
distance between connections. Table 6 gives an example
showing the relative cost of the DSL and the T-1 between
University of Southern California and St. Johns Health
Center 15 miles apart in the Greater Los Angeles Metropolitan Area.
Table 6 demonstrates that the initial investment for
the DSL is minimal since the WAN carrier pays for the
DSL Modem for the network connection. The lowest
Table 6. WAN Cost Using DSL (144 kB/s8 MB/s) and T-1
(1.5 MB/s) between USC and St. Johns Health Center
20 miles
DSL
T-1
Up front
Investment
Modems (2)
Minimal
Installation (2)
Monthly charge:
(the lowest rate)
Minimal
$40
None
Up Front
Investment
T1 DSU/CSUa
WAN interface (2)
Router (2)
T-1 Installation
T-1 Monthly
Charge:
$ 5000
$ 4000
$ 1000
$600
306
TELERADIOLOGY
Test Sites
CHLA/USC LAN (Childrens
Hospital/ U Southern California)
CHLA/USC-UCLA
CHLA/USC-Stanford U
CHLA/USC-UCSF
CHLA/USC-NLM (National
Library of Medicine)
CHLA/USC U Hawaii
*
Response
Time
(32 Bytes)
Throughput*
<1 ms
9.8 MBytes/s
4 ms
23 ms
24 ms
67 ms
2.7 MBytes/s
900 KBytes/s
700 KBytes/s
320 KBytes/s
76 ms
700 KBytes/s
units used are MBytes/s and KBytes/s which are different from those used
in Table 5.
User Friendliness
User friendliness includes both the connection procedure of
the teleradiology equipment at both the examination site
and the expert center, and the simplicity of using the
display workstation at the expert center.
User friendliness means that the complete teleradiology
operation should be as automatic as possible requiring only
minimal user intervention. For the image workstation to be
user friendly requires three criteria:
1. Automatic image and related data prefetch.
2. Automatic image sequencing and hanging protocol
at the monitors.
3. Automatic look-up table, image rotation, and unwanted background removal from the image.
Image and related data prefetch means that all necessary
historical images and related data required for comparison by the radiologist should be prefetched from the
patient folder at the imaging sites and send to the expert
center. When the radiologist is ready to review the case,
these prefetched images and related data are already
available at the expert center. Automatic image sequencing and hanging protocol at the display workstation
means that all these images and related data are sequentially arranged so that at the touch of the mouse, properly
arranged images and sequences are immediately displayed on the monitors. Prearranged data minimizes
the time required for the searching and organizing of data
by the radiologist at the expert center. This translates to
an effective and efficient teleradiology operation. The
third factor, automatic look-up table, rotation, and background removal, is necessary because images acquired at
the distant site might not have the proper look-up table set
up for optimal visual display, images might not be generated in the proper orientation, and might have some
unwanted white background in the image due to radiographic collimation. All these parameters have an effect on
the proper and efficient diagnosis of the images. Figure 4
shows an example of automatic splitting of a CT examination of both the chest and the abdomen into a chest
and an abdomen sequence for automatic display using
the concept of presentation of grouped procedures (PGP)
in IHE (Integrating the Healthcare Enterprise) profile
technology (10).
Image Compression
Teleradiology requires image compression because of the
slow speed and high cost of using WAN. For lossless image
compression, current technology can achieve between 3:1
and 2:1 compression ratios, whereas in lossy compression
using cosine transform based MPEG and JPEG hardware
or software, 20:110:1 compression ratios can be obtained
with acceptable image quality. The latest advance in image
compression technology is the wavelet transform (11 and
JPEG 2000), which has the advantages over cosine transform for higher compression ratio and better image quality,
however, hardware wavelet compression is not yet available. Some Web-based teleradiology systems use progressive wavelet image compression techniques. In this
TELERADIOLOGY
Requested
procedure
chest
Report:
chest
307
Report:
abdomen
Requested
procedure
abdomen
IMAGE
IMAGE
abdomenview
RIS/PACS
(3)
(4)
Modality
Performs
a single exam
(1)
Operator
groups 2
procedures
IMAGE
abdo
menview
(2 )
1. Private and Public Keys: Set up a method in assigning public and private keys between the examination site and the expert center.
2. Image preprocessing: To segment the object of interest in the image from the background (e.g., the head
in a CT image is the object of interest), and extract
patient information from the DICOM image header
at the examination site while the image is being
generated.
3. Image digest: To compute the image digest (digital
signature) of the object of interest in the image
based on its characteristics using mathematical
algorithms.
4. Data encryption: To produce a digital envelope
containing the encrypted image digest and the
corresponding patient information from the image
header.
5. Data embedding: To embed the digital envelope
into the background of the image as a further
security. The background is used because the
embedding would not alter the image quality of
the object of interest. In cases where the image has
no background, such as a chest radiograph, a more
involved lossless embedding technique can been
used.
6. The image with the embedded digital envelope is
sent to the expert site.
308
TELERADIOLOGY
where and to whom, and so on. The clients can view these
filtered images from the client workstation through the
web server. The clients can be referring physicians who
just want to take a look at the images or for radiologists to
make a remote diagnosis. Web-based teleradiology is very
convenient and low cost to set up because most technologies
are readily available, especially within the hospital intranet environment. The drawback is that since Web is a
general technology, the viewing capability and conditions
are not as good as that in a regular PACS workstation
where the set up is geared for radiology diagnosis. In order
to have full DCIOM image resolution for visualization
and manipulation at the clients, modifications have to be
made at the Web Server to receive full 12 bits/pixel data
from the PACS server, and additional display software at
the clients.
PACS and Teleradiology Combined
Teleradiology can function as a pure teleradiology operation shown in Fig. 5. In this operation, the teleradiology
management center serves as the operation manager. It
receives images from different imaging centers, 1,. . ., N,
keeps a record, but not the images, routes images to
different expert centers, 1,. . ., M according to need for
reading. Reports comes back to the management center,
it records the reading reports, forwards reports to the
appropriate imaging centers. The management center is
Site 1
Site N
RIS
RIS
Imaging
Imaging
center
center
Image/data
Report
Image/data
Report
Tele-radiology
management center
Image/data
Report
Image/data
Report
Expert
Expert
center
center
WS
WS
Site 1
Site M
TELERADIOLOGY
HIS
database
Reports
Imaging
modalities
Generic PACS
Generic PACS
Components
& Data Flow
Database
gateway
Acquisition
gateway
PACS
controller
& archive server
Application
servers
2
Workstations
5 (image)
Image
4 (report)
RIS
Report
Expert center
with management
Image
Imaging
center
WS
Report
4, 7
309
Image
Teleradiology
310
TELERADIOLOGY
WS
WS
PACS
Server
PACS
Server
Storage
Storage
PACS 1 PACS N
Local Back-Up
Archive
PACS N
PACS 1
Local
Back-Up Archive
Data
Grid
DICOM
IHE
PACS
Application
Teleradiology
Application
Computing
Grid
Report
Image
Expert
Center
Image
Grid
Infrastructure
Teleradiology
Application Layer
Image
Report
Report
Expert
Center
Image
Report
Management
Imaging
Center
Imaging
Center
Figure 7. Enterprise level large-scale PACS and teleradiology combined model using the grid
computing technology. The center ellipse of the figure is the grid computing infrastructure consisting of the data and computation grid with the DICOM standard and IHE workflow profiles. The
data grid handles the image data, and the computational grid takes care of the workflow and
management (see Chapter Section 19.2.2.4, Ref (4) for the concept of grid computing and the
functions of the data grid.) The top row above the dotted line is the enterprise PACS, which consists
of several PAC systems 1,. . ., N rectangles under numerals. The bottom row under the dotted line is
the pure teleradiology model described in Fig. 5. The connection between PACS and teleradiology in
the enterprise is not a straight line of data communication, instead it goes through the grid
computing infrastructure for resource allocation and management, as well as image data acquisition
and distribution.
Image
quality
Turnaround
time
Cost
Image
Capture
WS
Compression
Communication
Image
Integrity
TEMPERATURE MONITORING
311
INFORMATION SYSTEMS.
BIBLIOGRAPHY
1. Stahl JN, Zhang J, Zeller C, Pomerantsev EV, Lou SL,
Chou TM, Huang HK. Tele-conferencing with dynamic
medical images. IEEE Trans Inform Tech Biom 2000;4(1):
8896.
2. Zhang J, Stahl JN, Huang HK, Zhou X, Lou SL, Song KS.
Real-time teleconsultation with high resolution and large
volume medical images for collaborative health care. IEEE
Trans Inform Tech Biom 2000;4(1):178185.
3. Stahl JN, Zhang J, Chou TM, Zellner C, Pomerantsev EV,
Huang HK. A new approach to tele-conferencing with
intravascular ultrasound and cardiac angiography in a
low-bandwidth environment. RadioGraphics 2000;20:
14951503.
4. Huang HK. March, PACS and Imaging Informatics: Principles and Applications. Hoboken, NJ: John Wiley & Sons;
2004.
5. Huang HK. Teleradiology technologies and some service
models. Volume 20, Computerized Medical Imaging and
Graphics. 1996. p 5968.
6. DICOM Standard 2003, http://www.dclunie.com/dicomstatus/status.html#BaseStandard2001
7. HL7 Version 3.0: Preview for CIOs, Managers and Programmers,
http://www.neotool.com/company/press/199912_v3.
htm#V3.0_preview
8. Stahl JN, Tellis W, Huang HK. Network latency and operator
performance in teleradiology applications. J Digital Imag
2000;13(3):119123.
9. Huang HK. 2003, Research trends in medical imaging informatics. In: Hwang NHC, Woo SLY, editors. Frontiers in
Biomedical Engineering based on the Proc WCCBME (World
Congress for Chinese Biomedical Engineers Proceedings),
Chapt. 17, New York: Kluwer Academic Publisher; 2002; p.
269-281.
10. Carr C, Moore SM. IHE: A model for driving adoption of
standards. Comp Med Imaging Graphics 2003;Issues 23:
137146.
TEMPERATURE MONITORING
PETER FRASCO
Mayo Clinic Scottsdale
Scottsdale, Arizona
INTRODUCTION
The notion that illness and fever (elevation of body temperature above normal) are linked has been known since
the time of Hippocrates and Galen. However, the concept of
temperature as a quantifiable vital sign (like pulse rate and
blood pressure) that could be measured and recorded is a
relatively recent phenomena. Although the thermometer is
as ancient as the microscope and older than the stethoscope, its use as an instrument for physical diagnosis in
medicine is a relatively recent phenomenon (1).
The thermometer was invented in the fourteenth century, but its use in clinical medicine did not become commonplace until the early twentieth century (2). In 1625,
Sanctorio Sanctorius described a device that was used to
measure oral temperature. The practice of measuring body
temperature with mercury in a glass thermometer began in
the early eighteenth century with the work of the Hemann
Boerhaave in the Hollan and his students in Vienna (1,2).
One of his students, Anton DeHaen, noted changes in
temperature with shivering or fever. He also described an
increase in heart rate with increased body temperature (1).
His contemporaries were unimpressed and the thermometer was largely neglected until the nineteenth century.
In 1791, K.A. Wunderlich established the normal range of
body temperature from 36.3 to 37.5 8C after recording nearly
1 million readings in 25,000 patients (1,2).
312
TEMPERATURE MONITORING
SCALES
Temperature scales are constructed by defining two points
based upon a predictable and preferably linear change in
the physical property of a given substance at a constant
pressure, assigning temperature values to each and then
defining the unit of increment between the fixed points.
The relationship between temperature and the physical
property can be defined as follows:
tx ax b
where t is the temperature of the substance. This temperature changes as the property x of the substance changes.
The constants a and b depend on the substance used (e.g.,
mercury, ethanol, copper). The constants are also determined by specifying two points on the scale.
Heat
Heat is the form of energy that is transferred across a
boundary of a system at a given temperature to another
system at a lower temperature by virtue of the temperature difference between the two systems. This transfer of
energy can occur through radiation, conduction, convection, and evaporation. The standard unit of heat (in the
International System of Units, SI) is the calorie, which is
the amount of energy needed to raise the temperature of
1 g of water by 1 8C. The British thermal unit (Btu),
which is not frequently used in medicine, is defined as the
amount of heat needed to raise the temperature of 1 lb of
water by 1 8F (see discussion of temperature scales
below). Heat is transferred from the substance at the
higher temperature to the substance at the lower temperature.
Kelvin
A reading of 1 K [named after William Thompson, a.k.a.
Lord Kelvin (18241907)] is defined as 1/273.16(3.6609
103) of the thermodynamic temperature of the triple point
of pure water (3). The triple point of water is the point at
which the solid, liquid, and gaseous phases of water are in
equilibrium. Absolute zero, the absence of all heat, when
the pressure of the ideal gas is zero, is a temperature of 0 K.
The triple point of water in the Kelvin scale is 273 K. Kelvin
is the SI unit of temperature.
Centigrade
The centigrade scale was first described by Carolus Linnaeus. The freezing point of water was set at 0 and the
boiling point at 100.
Temperature
Temperature is defined as a measurement of the thermal
state of a matter, which determines whether it will give
heat to another substance, object or energy source, or
receive heat from it (3,4). Temperature is a measure of
the kinetic energy of the molecules or atoms of a substance.
This energy is directly proportional to the velocity of the
particles. Temperature will increase as heat energy is
added and will decrease as heat energy is lost.
Body Temperature
Body temperature is best defined as the measure of the
total kinetic energy within the body. This temperature
represents the net thermal effect of total body heat produc-
Celsius
The celsius temperature scale was originally defined by
Anders Celsius. He set the boiling point of water at 0 and
the freezing point at 100. As such, the Celsius scale was the
reverse of the Centigrade scale. In 1948, the centrigrade
scale was replaced with a newly defined Celsius scale that
was based upon setting the triple point of water at 0.01 8C
and the boiling point of water at 99.975 8C. The single
degree increments in the Celsius scale are equal in magnitude to those in the Kelvin scale. To convert from celsius
to kelvin the following formula can be used
K C 273
TEMPERATURE MONITORING
313
Liquid Expansion
Resistance Coil
Thermistor
Thermocouple
Liquid Crystal
Infrared
Accuracy
Sites
Cost
Design
0.2 8C
Oral, Rectal
Inexpensive
Expansion
0.1 8C
Skin
Expensive
Electrical
0.1 8C
All sites
Inexpensive
Electrical
0.1 8C
All sites
Moderate
Electrical
0.4 8C
Skin
Inexpensive
Chemical
0.3 8C
Oral Rectal Otic
Very Expensive
Radiation
Fahrenheit
The fahrenheit [named after Gabriel Fahrenheit (1686
1736)] scale (8F), like the Kelvin scale, is also based upon
the triple point and boiling point of water. The scale was
originally calibrated with a mercury thermometer using a
mixture of salt, ice and water as the zero point. The second
point was obtained when the salt was eliminated from the
ice and water. This was set at 30 8F. The boiling point of
water is 212 8F on this scale. The freezing point of water
was adjusted to 32 8F to allow the interval between the
triple point and boiling point to be a more rational number
(180).
To convert from Fahrenheit to Celsius the following
formula can be used
F 1:8 C 32
TYPES OF THERMOMETERS
A thermometer measures temperature of a system in a
quantitative way (Table 1).
NONELECTRICAL METHODS
Changes in Physical Dimensions (See Table 1)
Liquid Expansion Thermometers. The nonelectrical
methods of thermometry are loosely based upon the second
perfect gas law, Charles or Guy Lussacs law, which states
that at constant pressure the volume of a given mass of gas
varies directly with the absolute temperature (4). As heat is
added to a substance and temperature increases, the
volume of liquids and gases increase. Mercury and ethanol
are the most commonly used materials for the expansion
based or liquid in glass thermometers.
Ethanol is an alternative to mercury in glass thermometers. Although cheaper than mercury, ethanol thermometers may be unsuitable for high temperatures since
ethanol boils at 78.5 8C. Ethanol thermometers have a range
from 75 to 120 8C. This is unimportant in the clinical
setting of measuring and monitoring body temperature
but may be important in other aspects of medicine. In
addition, the scale of the ethanol-based thermometer may
be less linear than that of the mercury thermometer (3,5).
The design of the liquid expansion thermometer has
changed little in last century. The most sensitive location of
the liquid in glass thermometer is the bulb, where the
largest volume of liquid exists. However, the entire thermometer is temperature sensitive. These thermometers
are manufactured with a constriction at the lower portion
of the mercury column near the bulb. This prevents the
liquid from retracting into the bulb and allows the maximum temperature measured to be displayed until the
thermometer is shaken.
Liquid expansion thermometers are impractical for continuous use due to the inherent rigidity of the device, the
risk of breakage and the typically slow response (13 min)
compared to the techniques listed below.
Bimetallic. The sensing element is comprised of two
dissimilar metals bonded together in a coil, spiral, or disk.
One end of the coil is attached to a lever, the other end is
fixed to a point within the device. As temperature changes,
the metals expand (with heat) or contract (with cold) by
different amounts and the coil tightens or loosens, respectively, and moves a lever over a scale. These thermometers
are not very accurate, but are relatively stable over time,
require little maintenance, and are inexpensive. Bimetallic
thermometer sensitivity to small changes in temperature
can be increased by using a long strip wound into a tight
coil. The most common clinical application for the bimetallic spring thermometer is use with thermostat devices,
temperature alarm devices and operating room temperature monitoring.
The radius of curvature for a bimetallic thermometer is
inversely proportional to the difference between the bonding temperature for the strip and the temperature being
measured (3,5).
314
TEMPERATURE MONITORING
response to temperature. There are some important differences. Unlike RTDs, which are made conductors with a
positive coefficient to resistance, thermistors are made
from semiconductor materials that have a large negative
coefficient of resistance. Therefore, as temperature
increases, the resistance within the thermistor decreases.
ResistanceV AB=absolute temperature
The relationship between resistance and temperature is
nonlinear. In addition, thermistors operate within a relatively high resistance range (1 kV100 kV) compared to
RTDs.
A digital readout thermistor-based thermometer is illustrated in Fig. 1.
Thermistors are made from heavy metal oxides (cobalt,
iron, nickel, manganese, zinc). The metal is shaped into a
bead that is sealed into a small measuring tip to which
electrodes are attached. The tip can be sealed into a glass
tube, cardiac catheter or stainless steel probe. Thermistors
are accurate to 0.5 8C over a range of 80 to 150 8C (3).
Other advantages of thermistors include relatively small
size, low production cost, reproducibility, very high sensitivity, and resolution and relative insensitivity to shock
and vibration. Compared to RTDs, however, thermistors
are less stable and are more susceptible to internal heating
or self-heating. In addition, recalibration may be necessary
because the resistance of the metal oxide increases over
extended periods of time for unclear reasons. Calibration is
defined by the following equation (3,8):
Resistance R0 eb1=T1=T0
where R0 reference resistance measured at
T measured temperature; b material constant.
T0;
Thermocouple
When heat is applied to one end of a metallic conductor,
electrons at this hot junction acquire increased thermal
energy relative to those electrons at the unheated or cold
junction. The electrons diffuse from the hot junction to
the cold junction, and in doing so lose this thermal
energy. Heat is conducted along the conductor and an
+Vref
Resistor
Thermistor
Op amp
V0 to ADC input
TEMPERATURE MONITORING
Kc
Kh
A
B
dV
Reference junction
Junction
potential
mV
Measuring junction
T C
315
Temperature T C
Figure 3. Thermocouple.
316
TEMPERATURE MONITORING
Tb
TEMPERATURE MONITORING
317
Figure 4. (a) Liquid-crystal disk and contact-type (skin) thermistor. (b) Infrared otic (tympanic membrane) thermometer. (c) Contact-type thermistor for tympanic membrane temperature.
318
TEMPERATURE MONITORING
Esophagus
Intravascular
Urinary Bladder
The bladder temperature correlates well with other measures of core temperature. Bladder temperature is
recorded with specially modified urinary catheters. These
catheters are commonly used to monitor urine output
during surgical procedures or during treatment in the
intensive care unit. A thermistor or thermocouple is
attached to the patient end of the catheter.
Changes in bladder temperature during hypothermic
cardiopulmonary bypass with extracorporeal circulation
will occur later than changes in nasopharyngeal, tympanic
membrane, and pulmonary artery temperature.
Rectum
The rectal mucosa was previously used as a site for core
temperature measurement. It is now clear that the rectum
is a relatively peripheral site. As such, it does not accurately reflect core temperature. In fact, at times, rectal
temperature may exceed core temperature due to the heat
produced by metabolism of the fecal bacterial flora. At
other times, the presence of feces in the rectum may
insulate the probe from contact with the rectal mucosa.
In addition, the rectal veins receive blood from the lower
extremities. This blood can have a cooling effect on the
rectal temperature.
Rectal probes are seldom used for continuous temperature monitoring due the inaccuracies listed above. In addition, awake patients may find them uncomfortable.
Intermittent rectal temperature measurements are
often made in the pediatric population using mercury or
ethanol in glass thermometers. In addition, a digital
thermistor or thermocouple probe may be used in this
location.
Temperature Regulation
The bodys core temperature may change without any true
change in the total heat content due to redistribution of
heat to or from the periphery (7,1315). This occurs most
commonly during surgical procedures due to peripheral
dilatation secondary to anesthesia.
The temperature control center is located in the anterior
hypothalamus. The hypothalamic regulatory center receives
afferent input from peripheral skin receptors and initiates
appropriate responses, such as reduced heat loss through
skin vasoconstriction, increased heat production through
raised muscle tone, or shivering (7,1315). Impairment of
thermoregulatory control can occur due to a number of factors
including (7,1315): anesthetic drugs; hypoxemia; extremes
of age; shock (Blood loss or hypovolemia); hypothyroidism;
hypoglycemia; malnutrition; extreme exertion; central nervous system (CNS) dysfunction.
Heat production varies by age and gender. At rest, the
average male produces 1 kcalkg1 of heat per hour and the
average female 0.93 kcalkg1h1 (16,17). Heat production
occurs primarily by metabolic activity in the liver and skeletal
muscles. Heat production in skeletal muscle increases with
voluntary activity (movement and exercise) and shivering
(see below). With exercise, heat production can increase to 3
9 kcalkgh1 (16,17). This heat is transferred from the muscles to the blood supply of the muscular bed. This blood then
TEMPERATURE MONITORING
319
Convection is the transfer of heat secondary to air currents. Air adjacent to the skin is warmed by conduction. This
warmed is less dense and rises. As air flows over the body,
the current carries heat away from the body. Convective
heat flux is defined by the following equation (4,5,20):
Qcv gTs Tg
where g is the proportionality constant (Jg2K1), Ts is the
surface temperature, and Tg is the air temperature.
Forced convective heat loss is caused by gas flow caused
by external means (fan or pump). Free convective loss
occurs due to the gas flow that occurs secondary to temperature differences (4,5,18,20).
Clinical convective losses occur secondary to the
requirement of maintaining the air conditioner and/or
the air handling system at the colder settings due to multiple layers of sterile clothing worn by the surgical staff. In
addition, the rates of operating room air turnover may be
significantly higher than in other ambient settings. This
increase in air turnover serves to reduce the likelihood of
infection, but increases convective losses. Convective losses
can be reduced by trapping the layer of air between the skin
and external environment with a barrier, such as a thermal
blanket or forced air device (21).
Radiation heat loss occurs due to the transfer of heat in
the form of electromagnetic energy. The magnitude of heat
transfer is dependent on the surface area of the emitting
object (4,13,18). It is not dependent on the presence of a
material medium therefore no direct contact is required.
SUMMARY
Iatrogenic hypothermia predisposes the patient to profound physiological consequences, including delayed recovery from anesthesia, increased oxygen consumption,
increased vascular resistance, cardiac instability and
potential ischemia or infarction, coagulopathy, diminished
patient satisfaction, and increased recovery room costs. In
considering the need to provide the best patient outcomes,
hypothermia induced complications can and should be
prevented. Prevention of hypothermia requires monitoring
of body temperature. The devices that can be used vary in
accuracy, convenience and degree of invasiveness. Appropriate choices will influence patient outcome.
BIBLIOGRAPHY
1. Lyons A, Keiner M. The seventeenth century: anatomical and
physiological advances: The thermometer. In: Lyons A, Petrucelli R, editors. Medicine: An Illustrated History. New
York: Abradale Press; 1987. p 437439.
2. Pearce J. A brief history of the clinical thermometer. QJM
2002;95(4):251252.
3. Liptak B. Temperature Measurement. 3rd ed. Radnor (PA):
Chalton Book Company; 1993. p 134.
4. Halliday D, Resnick R, Walker J. Fundamentals of Physics.
7th ed. Hoboken (NJ): Wiley; 2005.
5. Parbrook G, Davis P, Parbrook E, editors. Basic Physics and
Measurement in Anaesthesia. 3rd ed. Oxford: ButterworthHeinemann Ltd.; 1990. p 344.
320
THERMISTORS
6. Chang H. Inventing temperature: measurement and scientific progress. Oxford: Oxford University Press; 2004. p 286.
7. Szocik J, Barker S, Tremper K. Fundamental principles of
monitoring and instrumentation. In: Miller R, et al., editors.
Anesthesia. Philadelphia: Churchill Livingstone; 2000. p
10531077.
8. Cork R. Temperature monitoring. In: Blitt C, Hines R, editors. Monitoring in Anesthesia and Critical Care Medicine.
New York: Churchill Livingstone; 1995. p 543556.
9. Collins P. Liquid Crystals: Natures Delicate Phase of Matter.
2nd ed. Princeton: Princeton University Press; 2002. p 204.
10. Joachimsson P, Hedstrand U, Tabow F, Hansson B. Prevention of intraoperative hypothermia during abdominal surgery. Acta Anaesthesial Scand 1987;31(1):330337.
11. Phillips P, Skov P. Rewarming and cardiac surgery: a review.
Heart Lung 1988;17(5):511520.
12. Cork R, Vaughn R, Humphery L. Precision and accuracy of
intraoperative temperature monitoring. Anesthesia Analg
1983;62:211217.
13. Sessler D. Mild perioperative hypothermia. N Engl J Med
1997;336:16301637.
14. Sessler D, Rubinstein E, Moayeri A. Physiologic responses to
mild perianesthetic hypothermia in humans. Anesthesiology
1991;75(4):594610.
15. Sessler D, Schroeder M. Heat loss in humans covered with
cotton hospital blankets. Anesth Analg 1993;77:7377.
16. Guyton A, Hall J. Textbook of Medical Physiology. 10th ed.
Philadelphia: Saunders; 2000. p 1064.
17. Schafer J. Body temperature regulation. In: Johnson L,
editor. Essential Medical Physiology. San Diego: Elsevier;
2003. 921932.
18. Fallacaro M, Fallacaro N, Rachel T. Inadvertent hypothermia. Etiology, effects and prevention. AORN Journal
1986;44(1): 54-760-1.
19. Evans J, et al. Cardiovascular performance and core temperature during transurethral prostatectomy. J Urol
1994;152: 20252029.
20. Bejan A. Convection Heat Transfer. 3rd ed. New York: Wiley;
2004. p 728.
21. Augustine S. Hypothermia in the post anesthesia care unit. J
Post Anesthesia Nursing 1990;5:254263.
See also BIOHEAT TRANSFER; INTEGRATED CIRCUIT TEMPERATURE SENSOR;
MONITORING IN ANESTHESIA.
THERMISTORS
PEDRO LOPES DE MELO
State University of Rio de
Janeiro
Brazil
INTRODUCTION
The normal body temperature of human beings is considered to be constant 37 8C. Heat energy is stored in the body
THERMISTORS
THEORY
Thermistor (the contracted name of thermally sensitive
resistor) is a general term used for both positive and
negative temperature coefficient types of semiconducting
thermal transducers. These devices are constructed of
ceramic materials whose electrical conduction properties
are temperature sensitive. At a fixed environmental temperature, a thermistor exhibits a specific ohmic value.
However, if the environment temperature varies, this
resistance changes. Thermistors are able to sense temperatures from 50 to 300 8C, which is a small range compared
with metal wire sensors. A platinum wire, for example, can
be used to measure temperature from 160 to 1000 8C.
This range, however, is much greater than most of the
medical temperature measurement tasks would require.
Thermistors usually have high negative temperature
coefficients (NTC), resulting in a decrease of the thermistor
resistance with increasing temperature. The negative temperature coefficient in nonmetallic materials (silver sulfide), was first observed by Michael Faraday in 1833, but it
was not until 1940 that thermistors where developed that
were able to produce reproducible results. The NTC thermistors are typically made of transition-metal oxides. The
most usual oxides are those of manganese, nickel, cobalt,
and iron (3,4). In the basic fabrication process, a mixture of
two or more metal oxide powders are first combined with
suitable binders, and are molded to a desired geometry.
Then the products are dried and sintered at an elevated
temperature. The units are finally coated with an epoxy
layer for final protection and stabilization. Varying the
types of oxides used, their relative proportions, the
sintering atmosphere, and the sintering temperature, a
wide range of resistivities and temperature coefficient
characteristics can be obtained. More detailed descriptions
of NTC manufacturing techniques can be obtained in Refs.
35. Since their first use in practical electronic thermometer in the early 1950s, thermistor technology has been
enhanced continuously, resulting in improvements that
probably situate this device as the most widely used temperature transducer for medical applications nowadays.
These devices have been developed to be very sensitive to
variations in temperature ( 3 to 5 8C), present excellent
321
THERMISTOR TERMINOLOGY
Dissipation constant (DC or d) is the amount of power
required to raise the temperature of the thermistor 1 8C
above the surrounding temperature in steady-state conditions (6). It means that the resistance changes by an
equivalent of 1 8C for each dissipation constant rating
(mW 8C1) for the selected device. It depends on the heat
transfer from the thermistor to its surroundings (by conduction through the leads, free convection in the medium
and radiation), the relative motion of the medium in
which the thermistor is located, as well as the thermal
conductivity. A typical value of the dissipation constant of a
thermistor with a 0.24 cm outer diameter, coated with
epoxi or phenolic layers, is 2 mW 8C1 in still air (7). Its
parameter increases with thermistor mass and in water is
510 times the value measured in air.
Maximum operating temperature is the maximum
body temperature at which the thermistor will operate for
an extended period of time with acceptable stability of its
characteristics. This temperature can be the result of
internal or external heating, or both, and should not exceed
the maximum value specified (6).
Self-heating is a process observed when a current
flowing through a thermistor causes sufficient heating
322
THERMISTORS
1 dR
RT dT
Because the relationship between resistance and temperature is not linear, a is a function of temperature and it
is usually specified over the temperature range where the
temperature variation is expected. One of the most
important characteristics of a thermistor is, without
question, its extremely high temperature coefficient of
resistance. A typical value is 4.3%8C1 at 37 8C.
Thermal time constant (TC or t) describes the heat
inertness of thermistors (5) and it is the time (s) required for
a thermistor to change 63.2% of the total difference between
its initial and final body temperature, when subjected to a
step function change in temperature under zero-power conditions. This parameter is directly affected by the mass of
the thermistor, the thermal properties of the medium surrounding the device, the thermal coupling to the environment, the motion of the medium, the conduction through the
leads, and the radiation losses. An epoxy coated thermistor
with a 0.24 cm outer diameter will typically have a time
constant of 0.75 s in stirred oil and 10 s in still air (7).
Interchangeability tolerance: The rated thermistor
parameters values are subject to manufacturing tolerances.
They are determined by the composition and structure of the
various metal oxides being used in the device production.
The result will be a variation from unit to unit within a
production lot, as well as from lot to lot. Interchangeability
tolerance is the value of how far a specific family of devices
may be from the nominal resistance versus temperature
curve. For example, if a family of devices has an interchangeability tolerance of 1.0 8C over the range from 0 to
70 8C, it means that, for this range, all devices of this family
are within 1.0 8C of the resistance versus temperature
curve. This feature results in accurate temperature
measurements to 1.0 8C, no matter the substitution of
thermistors. Modern thermistor technology results in the
production of devices with tight zero-power resistance
tolerances. Over the medical temperature range, interchangeable tolerances to 0.1 8C are typical (9,10).
THERMISTORS
T T0
R
ln 0
TT0 RT
323
2x
x2 c3
4 27
2x
x2 c3
4 27
where, x (a 1/T)/c and c b/c. The a, b, and c coefficients, can be solved measuring the thermistor resistance
(R1,R2,R3) at three different temperatures (T1,T2,T3) and
using simultaneously equation 5. The data calculated by
equations 5 and 6 will be accurate to better than
0.01 8C,
when T1 40 8C, T3 150 8C, jT1 T2j 50 8C and
jT2 T3j 50 8C. Parameters T1, T2, and T3 are evenly
spaced and at least 10 8C apart.
VOLTAGECURRENT CHARACTERISTICS
If a constant electrical power is applied to the thermistor its
temperature will first increase considerably, but this
change will decline with time. After some time a steady
state will be reached, where the power is dissipated by
thermal conduction or convection. The voltage drop on the
thermistor as a function of the flowing current under
conditions of thermal equilibrium is
V I dTT TA
dTT TA
RT
and
V
p
dTT TA RT
324
THERMISTORS
THERMAL CHARACTERISTICS
The power dissipated by a thermistor (P) is equal to the
rate at which thermal energy (H) is supplied to the thermistor. This is the same as the rate at which energy is lost
from the thermistor to its surroundings (HL), plus the rate
at which energy is absorbed (HA) (13,14).
P
dH dH L dHA
dt
dt
dt
10
The rate at which thermal energy is lost from the thermistor is proportional to the temperature raise of the
thermistor,
dHL
dTT TA
dt
11
THERMISTORS
12
where s is the specific heat and m is the mass of the thermistor. Thus, the heat-transfer equation for an NTC
thermistor, at any instant after the application of power
to the circuit, can be expressed as
P RI 2
dH
dT
dTA TA sm T
dt
dt
13
T TA
dt
sm T
15
325
b=TM 2
GTM =Gs 1
18
t
t
16
RT
kQ
R
4
RP
3
RP
RT
0
20
20
40
60
80
100 C 120
T
326
THERMISTORS
19
where RLO, RTM, and RHI are the thermistor resistance at the
low, mid, and high end of the range, respectively. In this
procedure, the addition of series resistor Rs forces the equivalent resistance of the fixed resistor thermistor to have zero
error along a linear temperature scale in the three points
chosen. The temperature range of the application determines
the maximum error. For example, if the range is taken to be
50 8C to 100 8C, the errors are 0 at 50, 25, and 100 8C, and
the errors elsewhere are distributed in an S-shaped. If the
temperature range is reduced, the errors become smaller;
being 2.0 8C over a 60 8C range, 0.05 8C over a 30 8C range,
and 0.01 8C over a 10 8C range. Another way to linearize
thermistors includes the use of a Wheatstone bridge. In most
applications, the bridge consists of a linear thermistor voltage divider and a fixed resistor voltage divider, as described
in Fig. 5a (21). This circuit is designed to produce 1 V at 25 8C
and 200 mV at 45 8C, with an output voltage that is linear
within
0.06 8C in this temperature range (Fig. 5b). Hoge
(22) showed that circuits based on resistors (serial, parallel,
or bridge) are equal in their ability to linearize thermistor
1 VOLT
(a)
T1
R3
OUTPUT
METER
R1
200
VOLTAGE OUTPUT (V)
(b)
R2
NORMAL
LINEAR RESPONSE
100
ACTUAL
OUTPUT RESPONSE
0
25
30
35
40
45
TEMPERATURE (C)
Figure 5. Use of a thermistor in a Wheatstone bridge for temperature measurements (A) and respective output voltage as a
function of temperature (B) (courtesy of Alpha Sensors, 2121
Palomar Airport Rd., Carlsbad, CA 92009, USA).
THERMISTORS
including microcontrollers, in many cases the mathematical functions may contain complex polynomial and exponential functions, placing a great burden on the program
memory, RAM, and execution speed of most low cost
devices. Digital piecewise linear interpolation may be a
good choice for sensor linearization in such systems due to
its fast execution speed, reduced program memory requirements, and easy of implementation (33).
ELECTRONICS FOR TEMPERATURE MEASUREMENTS
In the circuit project, simulation and analysis environment, SPICE subcircuits for thermistor modeling are useful, allowing for a realistic simulation of thermistor
parameters for all standard analysis [transient, alternating current(ac), and dc]. Useful subcircuits have been
described by Keskin (14), Hagerman (34) and Wangenheim
(35), and are also commercially available (http://www.catena.uk.com; http://www.intusoft.com/products). As discussed earlier, there are a variety of circuits in which
thermistors may be used for temperature measurements.
Caution must always be taken, however, to insure that the
power dissipated in the thermistor is held at a minimum
and that the current flow is insufficient to cause selfheating, since temperature measurements require that
the thermistor be operated in a zero-power condition.
The most common technique implies the use of a constant
current source, and the measurement of the voltage developed across the thermistor.
327
would prevent thermal runaway in thermistors. The simplest circuit that can approximate a current source is a
high voltage source with a high resistance connected in
series (voltage divider), as can be seen in Fig. 7. In this
circuit, the output voltage is taken across the fixed resistor,
and, the higher this resistor in relation to the thermistor
resistance, and the higher the voltage, the closer this
circuit will conform with an ideal current source. From
the plot of the output voltage (Fig. 7b) it can be observed
that there is a range of temperatures where the circuit is
reasonably linear with good sensitivity. However, this
simple circuit does not act like an ideal current source,
since modifications in the thermistor resistance introduces alterations in current. An even better approximation to the desired current source would be obtained using
standard circuits based on operational amplifiers (16,36).
Integrated current sources are also useful, allowing for
the configuration of regulated current sources of varying
magnitudes. Fig. 8 shows a typical example, which is
based on a device containing two low current regulators
(37). One of current regulators supplies 100 mA to the
thermistor. The temperature of the thermistor is converted into a voltage that is increased by R3, filtered by
R2-C1 and amplified by U1B. The second current source is
used to provide the reference voltage in combination with R1
and U1a. This circuit is a useful framework for thermistor
temperature measurements using analog-to-digital
converters (37).
Wheatstone Bridges
Current Sources
In the section dedicated to the thermal characteristics of
thermistors, it was shown that the use of current source
328
THERMISTORS
(a)
SIMPLE
VOLTAGE DIVIDER
RT
es
eo(T)
eo (T)
(b)
Temperature
+5 V
For applications in which digital processors or microcontrollers are used for data acquisition and signal processing,
the transducer response must assume a form suitable for
conversion to digital format. Temperature-to-frequency or
temperature-to-time interval conversions are convenient
methods to measure temperature in this case, since they
permit an easy and low cost interface, no ADC is needed
and only one bit of input is necessary (6). Another advantage is that the optical isolation circuits used in this kind of
application presents lower cost than that used in linear
systems. Fig. 9 shows two simple circuits in which the
frequency of oscillation varies with the temperature.
Because a thermistor resistance varies with temperature,
the RC time constant will change accordingly. And since the
555 timer determines the frequency corresponding to
the RC time constant, the actual resistance is proportional
to the number of counts recorded by the 555 timer (Fig. 9a).
The frequency, or the number of counts in a given time
window, can be easily converted to a temperature value
(38,39). In the circuit described in Fig. 9(b), the thermistor
is placed in the feedback loop of a histeresis-based oscillator, and the output frequency is related to temperature,
+5 V
0.10
mA
0.10
mA
VREF
R1b
+5 V C3
8 100 nF
2 U1a
1
3 +
4 TLV2472
R1a
C2 10 nF
Rfa
Rfb
Rg
VIN
R2
10 k
C1
10nF
Thermistor
6 U1b
7
5
+
TLV2472
VOUT
R3
Figure 8. Circuit containing two integrated low current regulators. Courtesy of Texas Instruments
Inc. 13532 N. Central Expressway M/S 3807 Dallas, Texas, USA (Adapted from (37) with permission).
THERMISTORS
+5V
/RTCRST
TRIG
TMRDONE
to Z180
/DREQ0 and /INT1
329
20
OUT
(a)
R0
R2
In handheld applications, accurate temperature measurement can easily be accomplished by interfacing a Wheatstone bridge including a thermistor and a digital voltmeter
integrated circuit, as illustrated in Fig. 11. The IC is
comprised of an analog-to-digital converter with built-in
3 12 digits LCD driver providing resolution of 0.1 8C. This
digital thermometer makes it possible to achieve an overall
system accuracy of 0.4 8C from 0 to 100 8C. Anytime more
than one thermistor temperature probe must be measured,
a scanning digital panel meter may be a useful adjunct.
Fig. 12 shows another simple circuit, using a microammeter in series with a potentiometer and a thermistor
connected to a potential source. The meter can be calibrated in terms of temperature, providing a system usually
used in low cost applications (6).
R1
(b)
Figure 9. Simple, low-cost nonlinear temperature to frequency
converters based on oscillators constructed around 555 (A) and
operational amplifier (B). Circuit (A) is a courtesy of ZWorld, 2900
Spafford Street Davis, California 95616, USA, and circuit (B) is
from Interfacing Sensors to the IBM PC, by W. J. Tompkins and J.
G. Webster, 1988. (Reprinted by permission of Prentice-Hall).
AD741J
2V
+15V
CAL
0C
ANALOG OUT
0-10V-0-100C
FREQUENCY
OUTPUT
50k
RG(9950)
AD580
YSI
FURNISHED
PULSE
ENGINEERING
PE3843
452
4k7
500R
FS
CALIBRATE
SET FOR
100kHz AT
10V FULL SCALE
YSI
44018
THERMISTOR
NETWORK
4k7
+15
GATING
INPUT
(OPTIONAL)
330
THERMISTORS
R7 = 1.5K
R8 = 100K
R9 = 470K
R10 = 15K
C1 = 100pF
C2 = 0.1
C3 = 0.22
C4 = 0.1
T1
T2
To
LCD
Figure 11. Digital thermometer based on 3-1/2 digits voltmeter (courtesy of Alpha Sensors, 2121
Palomar Airport Rd., Carlsbad, CA 92009, USA).
Temperature
to period
converter
Thermistor
RT
Switch
Q1
AGC
10K
500 kHz
Osc.
Figure 12. A simple low-cost circuit for temperature measurements based on a microammeter (from Interfacing Sensors to the
IBM PC, by W. J. Tompkins and J. G. Webster, 1988, Reprinted by
permission of Prentice-Hall).
To
temperature
display
THERMISTORS
R+
331
REFERENCE
VOLTAGE-TO-PVM
CONVERTER
T1
T2
I/O
MAX6691
T3
T4
(a)
Vcc
TOP VIEW
T1
T2
T1
T3
T2
T4
T3
R
T4
VCC
1
10
MAX6691
I/O
10k
MICROCONTROLLER
N.C.
GND
R+
REXT
(b)
Figure 14. Functional diagram (A) and typical application circuit (B) of the MAX6691,
four-channel temperature-to-pulse-width converter. Copyright Maxim Integrated Products
(www.maxim-IC.com). Used by permission.
332
THERMISTORS
AVDD DVDD
REF IN(+)
AVDD
RTD 1
AD7711
2.5 V
REFFERENCE
RTD 2
REF OUT
AIN1(+)
VBIAS
DIGITAL
FILTER
PGA
MUX
SYNC
AIN2
MCLK IN
CLOCK
GENERATION
MCLK OUT
SERIAL INTERFACE
AGND
OUTPUT
REGISTER
CONTROL
REGISTER
DGND
VSS
A0
DRDY
(a)
+5V
AVDD
DVDD
VBIAS
RTDA 1
REF OUT
REF IN (+)
R1
SYNC
AD
AIN 1(+)
RT
Figure 15. Functional diagram (A)
and typical application circuit (B) of
the AD7711, 24-Bit Sigma-Delta,
Signal Conditioning ADC. Reproduced from Ref. (19) with permission.
THERMISTOR
0.3K1A1
AIN 1(-)
AD7711
RFS
TFS
DRDY
SCLK
SDATA
DVDD
DVDD
SS
PC3
PC0
PC1
PC2
SCK
68HC 11
MISO
MOSI
(b)
ment a flexible system for application is medical thermometry (6,44). These PC-based DAQ systems requires some
signal conditioning hardware to interface the thermistor to
the measurement device, such as a plug-in DAQ board
(Fig. 16). The DAQ board or module performs the
analog-to-digital conversion. A system to interface the thermistor and its output signal to this stage should include an
excitation current or voltage source, signal amplification,
low pass filtering and isolation signal conditioning hardware, which serves to electrically isolate the thermistor
sensors from the measurement system, protecting the
patient. Concerning the last topic, it is important to point
out that electrical-safety codes and standards in healthcare facilities must always be strictly followed (45). Several
of useful circuits to perform these tasks were discussed
earlier. A typical plug-in DAQ board has eight to 16 analog
THERMISTORS
333
Figure 16. Block diagram of a PC-based DAQ system for temperature measurements with thermistors
(courtesy of National Instruments Corporation, Austin Texas, USA).
334
THERMISTORS
THERMISTORS
5 mm
Passive thermistor
1 mm
Vo
V(t)
Active thermistor
Measurement field
~4 mm
Cardiovascular Monitoring
Cardiac output, the volume of blood ejected by the heart
each minute, is a key parameter in cardiovascular medicine, which is used to obtain diagnostic information about
the heart and for continuous monitoring of heart function
in critically ill patients. The thermodilution method uses
thermistor type catheters to estimate this parameter.
The tip of a SwanGanz catheter is inserted into a large
vein, typically one in the right side of the neck, and advances
through the right heart into the pulmonary artery (Fig. 18).
Other sites can be used for catheter insertion (e.g., the
groin or the arm). A cold saline or a dextrose solution,
whose volume and temperature are known, is injected into
the blood stream through one of the catheter lumens. The
solution mixes with the blood in the right atrium and is
diluted as it is carried downstream to a thermistor located
at the surface of another catheter lumen. At the thermistor
location, the temperature of the blood-injected mixture is
measured over a period of time, and then the cardiac output
(efficiency) is computed from this temperaturetime
response data.
At the level of the capillary network, the tissue blood
flow (perfusion) is a primary factor in the local transport of
heat, drugs, oxygen, nutrients, and waste products. This
fundamental parameter holds the key to the diagnosis and
subsequent treatment of numerous medical problems. The
high sensitivity to small changes in temperature shown by
335
Temperature
336
THERMISTORS
R1
R2
Ru
Linearizer
Rt
Figure 20. Feedback circuit used in thermal convection flowmeters. From Medical Instrumentation:
Application and Design, by J. G. Webster. Reprinted
by permission of John Wiley and Sons, Inc.
amplifier as presenting infinite constant gain and bandwidth, the bridge is always statically maintained balanced,
and hence the thermistor resistance and temperature are
constant. The sensor resistance is maintained constant
equal to R1 under any operating condition. This circuit
operates satisfactory if ambient temperature is constant. If
changes in ambient temperature are expected, a second
unheated thermistor can be included in the circuit to
compensate it (Rt in Fig. 20). One of the main advantages
of this configuration is that the high negative gain feedback
divides the sensor time constant by a factor equal to the
loop gain, improving the frequency response (52). Thermistors loose heat at a rate dependent on the local mass
flow, temperature, specific heat, kinematic viscosity, and
thermal conductivity of the fluid. Thus, when a patient
exhales through an breathing device in which the thermistor is mounted, it is cooled and the circuit needs to provide
more electrical power to keep the thermistor temperature
constant. This power is proportional to the airflow. When
gas flow properties are sufficiently constant, the output
voltage of these circuits is a nonlinear function of mass-flow
rate only. Linear massflow relationships may be obtained
using a linearization stage (Fig. 20), based on analog or
digital implementations of piecewise linear or polynomial
approximations (53).
Since the thermistor is cooled equally for both directions
of velocity, the system with a single sensor provides an
output of the same polarity, independent of the flow direction. This feature limits the use of these sensors to unidirectional flow, which can be satisfactory in some
applications, as for example, in forced expiratory testes.
Directional sensitivity can be provided by putting multiple
sensors at separate points along the flow.
Speech Therapy
Spoken language is a highly developed skill. It involves the
use of parts of the brain that deal with hearing, understanding speech, sound production, and conversion of the
thoughts into speech. Patients suffering from cleft palate or
similar defects exhibit a type of speech that is characterized by excessive nasal escape of air and by an abnormal
resonance compared with normal speakers. This may be
treated by plastic surgery, palatial prostheses, speech
therapy, or even a combination of these treatments (54).
Trained listeners and also experienced therapists have
been already used to detect the presence of nasal air
escape. These evaluations are, however, subjective and
hinder objective comparisons with previously made assessments, especially if these were made by another therapist
(55). In order to allow a qualitative and quantitative analysis of nasal air escape, anemometers based on thermistors were proposed (5456). Fig. 21 is a cross-section
showing details of the device. The thermistor is positioned
in the longitudinal path of the nasal airflow. The system
uses a Wheatstone bridge; in one arm of the bridge a
thermistor is connected, while in the opposite arm a second
thermistor is used, as temperature-compensation element.
In the practical use of this kind of system, clear differences
were obtained when nonnasal and nasal subjects were
asked to talk a nonnasal word (cheese) and a nasal word
(missing) (54). The system can provide a numerical figure
of merit to indicate the extent of the defect and the effectiveness of a treatment, as, for example, palatal training.
Sleep Medicine
One of the most used methods to sense breathing patterns
is to detect airflow using a nasal thermistor sensor. The
principle here is that of exhaled air (37 8C) being slightly
warmer than inhaled air (room temperature), resulting in
modifications in the thermistor resistance correlated with
the respiration rate. The small size of the thermistor
contributes to prolonged, minimally intrusive measurements of breathing pattern, which are particularly important for respiratory surveillance in newborn intensive care,
biofedeback studies, and cyrcadian rhythm analysis (57).
These characteristics also made thermistors a traditional device in the diagnostic of sleep-disordered breathing (SDB) (58), which is a widespread disease estimated to
be present in 24% of middle-aged adults. In these
patients, the pharyngeal airway narrows with sleep onset,
initially producing harsh respiratory breathing with some
evidence of inspiratory flow limitation. Then, with further
narrowing snoring is generated, and finally there is a
complete collapse producing a full obstructive sleep apnea
(OSA). Even if upper-airway obstruction is incomplete
(hypopnea), increased upper airway resistance will still
cause clinical symptoms similar to OSA because of respiratory effort-related arousals. Although rare compared to
obstructive events, sleep apnea episodes can also be present in the absence of upper airway obstruction. In this
case, known as central sleep apnea (CSA), the apnea events
results from a decreasing in central controller output to the
inspiratory pump muscles. The classic daytime manifestation of SDB is the excessive sleepiness, although other
THERMISTORS
337
Air valve
Nose position
Air ring
Air flow
Microphone
Thermistor
To the
bridge
To audio amplifier
Inspiration
4
Arbitrary units
Expiration
10
15
Time (s)
20
25
338
THERMISTORS
0.81 mm
Capillary tube filled
with resin
z
x
5 mm
Geriatrics
0.6 mm
7 mm
Heated thermistor
x
2.5 mm
y
2.5 mm
2.5 mm
Figure 23. Thermistor thermal probe for the evaluation of thermal conductivity and the thermal diffusivity of biomaterials
(Reproduced from (61) with permission# 2001 IEEE).
BIBLIOGRAPHY
1. Guyton AC, Hall JE. Textbook of Medical Physiology. 10th
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3. Lavenuta G. Negative temperature coefficient thermistors.
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sensors. J Electroceramics 1998;2(4):273282.
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Tompkins WJ, Webster JG, editors. Chap. 7. Interfacing
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7. Anonymous (1998). Technical Notes, [Online]. Alpha Sensors,
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8. Anonymous (2002). General technical information [Online].
Epcos-Electronic Parts and Components. Available at http://
www.physics.leidenuniv.nl/edu/courses/Experimentele%20Natuurkunde/NTC.pdf). Accessed 2005, March 11.
9. Anonymous (2001). YSI Precision Medical Probes and Accessories Catalog, [Online]. Ysi Corporation. Available at http://
http://www.advindsys.com/ysi.htm. Accessed [2005, March
11].
10. Anonymous (No date). Thermistors catalog, [Online]. Honeywell Corporation (Fenwall). Available at http://content.honeywell.com/sensing/hss/thermal/product/thermisters.asp.
Accessed 2005, March 17.
11. Anonymous (No date). Thermistor glossary, [Online]. RTI
Electronics Inc. Available at http:// http://www.rtie.com/
ntc/glossary.htm. Accessed 2005, March 11.
12. Anonymous (2004, December, 14). Application Notes,
[Online]. Ametherm Inc. Available at http://www.ametherm.com/ Aplications/. Accessed 2005, March 11.
THERMISTORS
13. Anonymous (No date). NTC Thermistors, [Online]. Thermometrics Inc. Available at http:// http://www.thermometrics.com/assets/images/ntcnotes.pdf. Accessed 2005, March 11.
14. Keskin AU, Yanar TM. Steady-state solution of loaded thermistor problems using an electrical equivalent circuit model.
Meas Sci Technol 2004;15:21632169.
15. Sheingold DH. Transducer Interfacing Handbook. Noorwood
(MA): Analog Devices; 1981.
16. Normann RA, Principles of Biomedical Instrumentation.
New York: John Wiley & Sons; 1988.
17. Anonymous (2002). Application Notes [Online]. EpcosElectronic Parts and Components. Available at http://www.epcos.com/inf/50/db/ntc02/00290045.pdf. Accessed 2005, March 11.
18. Beakly WR. The design of thermistor thermometers with
linear calibration. J Sci Instrum. 1951;28:176.
19. OGrady A. Building a more perfect
union: combining therP
mistors and high-resolution
D A/D converters, Sensors
Online Available at www.sensorsmag.com/articles/0100/42/
main.shtml, Accessed 2000.
20. Lyons P, Waterworth P. The use of NTC thermistors as
sensing devices for TEC controllers and temperature control
integrated circuits, technical report, Betatherm Ireland Ltd.
21. Anonymous (1998). Application Notes, [Online]. Alpha Sensors, Inc. Available at http://www.alphasensors.com/tappnotes.html. Accessed 2005, March 11.
22. Hoge HJ. Comparison of circuits for linearizing the temperature indications of thermistors. Rev Sci Instrum 1979;50:(3).
23. Sheingold DH. Nonlinear Circuits Handbook. Noorwood,
(MA): Analog Devices; 1976.
24. Sundqvist B. Simple, wide-range linear temperature-tofrequency converters using standard thermistors. J Phys E
Sci Instrum 16:261264.
25. Patranabis D, Ghosh S, Bakshi C. Linearizing transducer
characteristics. IEEE Trans Instrum Meas. 1988;37:6669.
26. Sengupta RN. A widely linear temperature to frequency
converter using a thermistor in a pulse generator. IEEE
Trans Instrum Meas 1988;37:6265.
27. Slomovitz D, Joskowicz J. Error evaluation of thermistor
linearizing circuits. Meas Sci Technol 1990;1:12801284.
28. Kaliyugavaradan S, Sankaran P, Murti VGK. A new compensation scheme for thermistor and its implementation for
response linearization over a wide temperature range. IEEE
Trans Instrum Meas 1993;42(5):952956.
29. Kaliyugavaradan S, Sankaran P, Murti VGK. Hardware
linearization of thermistor response using series-parallel
resistors for temperature-to-time conversion. Meas Sci Technol 1994;5:786788.
30. Woodwards S. Pseudologarithmic thermistor signal conditioning spans wide temperature range, EDN 2005;50(1):66
67.
31. Ghosh D, Patranabis D. Software linearization of thermistor
type nonlinearity. IEE Proc Circuits Devices systems
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32. Finnie B. Software linearization techniques for thermistors.
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33. Day J, Bible S. (2004). Piecewise linear interpolation on PIC
12/14/16 series microcontrollers, application note no. 942.
[Online]. Microchip Technology Inc. Available at http://
ww1. microchip.com/downloads/en/AppNotes/00942A.pdf.
Accessed 2005, March 11.
34. Hagerman J. Model thermistors with spice. Elect Design
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35. Wangenheim L. SPICE subcircuit models thermistors. EDN
July 1997.
36. Boylestad RL, Nashelsky L. Electronic Devices and Circuit
Theory. Englewood Cliffs (NJ): Prentice-Hall; 2001.
339
37. Bishop J. Thermistor temperature transducer-to-ADC application. Analog Appl J (Texas Instr Inc). 2000; 4447.
38. Joyce D. (No date). Practical aspects of thermistors, Technical note no. 124. [Online]. Zwold Inc. Available at http://
www.zworld.com/support/techNoteswhitePapers.shtml.
Accessed 2005, March 11.
39. Anonymous (March, 2004). A high resolution/precision thermometer using ST7 and NE555, [Online]. ST Microelectronics, Application note no. AN1755. Available at http:// http://
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40. Wei D, Saidel GM, Jones SC. Thermal method for continuous
measurement of cerebral perfusion. Med Biol Eng Comput
1994;32(5):481488.
41. Evans NE, Hajnayebi HR. Clinical temperature acquisition
using proximity telemetry. J Biom Eng 1991;13:8386.
42. Baker B. Thermistors in single supply temperature sensing
circuits, AN685, Microchip Technology Inc., 1999.
43. Anonymous (2002). Four-channel termistor temperatureto-pulse-width converter, datasheet, [Online]. Maxim Integrated Products. Available at http://www.maxim-ic.com.
Accessed 2005, March 11.
44. Potter D. (June, 1995). Measuring temperature with thermistors a tutorial, [Online]. National Instruments Inc., Application note no. 65. Available at http:// http://www.seas.upenn.
edu/courses/belab/ReferenceFiles/Thermisters/an065.pdf.
Accessed 2005, March 11.
45. Olson WH. Electrical safety. Webster JG, editor. Medical
Instrumentation: Application and Design. 3rd edition.
New York: John Wiley & Sons; 1998.
46. Harrison RM, Smith SD, Roberts JA. Testicular temperatures measured by thermistor probe and contact thermography. Fertility Sterility 1990;54(1):173174.
47. Thoresen M, Whitelaw A. Cardiovascular changes during
mild therapeutic hypothermia and rewarming in infants
with
hypoxic-ischemic
encephalopathy.
Pediatrics
2000;106:9299.
48. Sakuragi T, Mukai M, Dan K. Deep body temperature during
cardiopulmonary bypass. Br J Anaest 1993;71(4):583585.
49. Dollberg S, Rimon A, Atherton HD, Hoat SB. Continuous
measurement of core body temperature in preterm infants.
Am J Perinatol 2000;17(5):257264.
50. Muir IH, Bishop PA, Lomax RG, Green JM. Prediction of
rectal temperature from ear channel temperature. Ergonomics 2001;44(11):962972.
51. Martin GT, Bowman HF. Validation of real-time continuous
perfusion measurements. Med Biol Eng Comput
2000;38:319325.
52. Webster JG. Measurement of flow and volume of blood.
Webster JG, editor. Medical Instrumentation: Application
and Design. 3rd edition. New York: John Wiley & Sons; 1998.
53. Primiano Jr. FP. Measurement of the respiratory system.
Webster JG, editor. Medical Instrumentation: Application
and Design. 3rd edition. New York: John Wiley & Sons; 1998.
54. Besar SS, Kelly SW, Greenhalgh PA. Nasal airflow measurement using a compensated thermistor anemometer, Part 1
system desciption and quantitative analysis.. Med Biol Eng
Comput 1989;27:628631.
55. Besar SS, Kelly SW, Greenhalgh PA. Nasal airflow measurement using a compensated thermistor anemometer, Part 2
Computer signal processing and quantitative analysis. Med
Biol Eng Comput 1990;28:127132.
56. Mirlohi HR, Kelly SW, Manley MCG. New technique for
assessment of velopharingeal function. Med Biol Eng Comput
1994;32:562566.
57. Jovanov E, Raskovic D, Hormigo R. Thermistor-based Sensor
for circadian rhythm evaluation. Biomed Sci Instr
2001;37:493497.
340
THERMOCOUPLES
Further Reading
Books: The following books contain several useful information concerning thermistors, its use and instrumentation. Tompkins
WJ, Webster JG. Eds. Design of Microcomputer-Based Medical
Instrumentation. New Jersey: Prentice Hall; 1981.
Enderle J, Blanchard S, Bronzino J. Introduction to Biomedical
Engineering. London: Academic Press; 2000.
Doebelin EO. Measurement Systems: Application and Design.
New York: McGraw-Hill; 1990.
Cobbold RSC. Transducers for Biomedical Measurements: Principles and Applications. New York: John Wiley & Sons; 1974.
Papers: Thermistor general characteristics and technology: Keskin AU. A simple analog behavioral model for NTC thermistors
including self-heating effect. Sensors and Actuators-A 2005;
118-2:244247.
Veijola T. Electrothermal simulation models for NTC and
PTC thermistors. Proceedings of CSC 98 1998;2, Piraeus:
950955.
Broughton MB. Analysis and design of almost-linear one thermistor temperature transducers. IEEE Trans Instrum Meas 1974.
23(1):15.
Jung JS, et al. Reliability evaluation and failure analysis for NTC
thermistor. Int J Mod Phys B 2003;17(89):12541260.
Pathan ZB, Shaligram AD. A PC-based characterization set-up for
reliable parameter testing of thermistor. Indian J Pure Appl
Phys 1995;33(4):215219.
Technical Reports
Doug C. Implementing Ohmmeter/Temperature Sensor. AN512,
Microchip Technology Inc.
Rodger R. Resistance and Capacitance Meter Using a PIC16C622.
AN611, Microchip Technology Inc.
Joyce D. (No date). Practical aspects of thermistors, Technical note
no. 124. [Online]. Zwold Inc. Available at http://www.zworld.
com/support/techNoteswhitePapers.shtml. Accessed 2005,
March 11.
THERMOCOUPLES
JOAKIM WREN
DAN LOYD
Linkoping University
Linkoping, Sweden
INTRODUCTION
Accurate temperature measurement is of utmost importance in many medical, biological, and biomedical applications. Technological development has increased both
the performance and the range of equipment for temperature measurement, but at the same time the apatite for
better measurements has increased as well. Opposite to
what might be expected, this in fact increases the
demands on the choice and especially the use of equipment for temperature measurement, as aspects associated
with the particular application becomes relatively more
important.
Despite the large variety of sensors and associated
instrumentation, there is a very limited amount of principles or physics behind the different sensor types, at least
when the most widely used sensors are considered (1);
thermocouples, thermistors, and resistance based sensors
(e.g., Pt-100). A thermocouple is an active sensor meaning
that by itself it can give rise to a detectable signal. Thermistors and resistance-based sensors are passive as they
demand an outer-power source. What all these sensors
THERMOCOUPLES
341
T1
T2
T1
T2
B
Since the junctions are electrically connected and subject to different electrical potentials, a current will flow in
the circuit; thus, thermal energy is converted into electric
energy (see, e.g., Ref. 4). The current flow makes the
Seebeck effect related to the Peltier and Thomson effects
(see, e.g., Ref. 5). Peltier discovered in 1834 that if a current
flows in a circuit made of two dissimilar conductors as in
Fig. 1, one of the junctions becomes cold and the other
junction hot. Thomson later found that for a circuit subject
to a temperature gradient (heat flux), heat is rejected in
any point where current and heat flows in the same direction, and is absorbed where the flows are countercurrent.
If a voltmenter is inserted in the circuit, as in Fig. 2b, it
is possible to measure the EMF and relate it to the junction
temperatures, as the voltage is dependent on the difference
between temperatures T1 and T2. Temperature measurement using a thermocouple is in fact measurement of a
temperature difference between the two junctions.
It is important that the voltmeter has a sufficiently high
resistance to keep the current small in order to eliminate
disturbances related to the Peltier and Thomson effects
(see, e.g., Ref. 5). This is normally not a problem, as modern
voltmeters have sufficiently high impedance for these
effects to be completely negligible.
Before modern measurement systems became available,
the thermocouple was normally used by keeping one of the
junctions (the reference junction) at a known temperature;
typically an insulated ice bath that is very close to 0 8C,
whereas the other junction (the sensor) was used for temperature measurement. The measured voltage is proportional to the temperature difference between the junctions,
A
Tref
T1
V
Tref
B
342
THERMOCOUPLES
and since the ice bath temperature is known, the temperature of the other junction can be determined if the thermoelectric properties of the wires are known.
Today, the reference junction is more or less always
integrated in the measurement system. The determination
of the reference temperature is normally optimized for the
instrument at room temperature (2025 8C), although temperatures close to this interval can often be used accurately
for most instruments. The circuit corresponding to a standard connection is given by Fig. 2, where the reference
temperature is measured at the transition between the
thermocouple leads (or extension leads) and the instrument connection. For two conductors A and B, the relation
between the sensor temperature T1, the reference temperature Tref and the measured EMF (voltage, V) follows the
equation
Z T1
Z T1
Z T1
SA TdT
SB TdT
SAB TdT
1
V
Tref
Tref
Tref
Figure 3. An example of a circuit for temperature measurement using a thermocouple type K. The thermocouple controller
AD597 (Analog Devices, Norwood, MA)
contains a cold junction compensation circuit, and the OP-amplifier TS912ID
(ST Microelectronics, Geneva, Switzerland)
amplifies the output V OUT so that 0 V
equals 0 8C and 5 V equals 100 8C with the
present impedances. The thermocouple is
connected to the IN and IN connections, and the low pass filtered voltage
supply is connected at V. There are
several manufacturers of similar circuits;
for details see the companies productspecific information.
temperature range, and tolerance to different environments. Type K is the most commonly used and it is a good
compromise of price and performance for many situations,
although other types might be the choice for very high/low
temperatures, hostile environements, and so on. Perhaps
the most important difference between the various types is
the output signal determined by the relative Seebeck coefficient of each material. Types S, B, and R contain platinum
and are therefore more expensive than the others, but they
are also more stable in, for example, e.g., oxidative environments.
There are organizations/national organizations that
provide standards for thermocouples, but the standards
of the IEC are internationally recognized and should be
followed whenever possible. The IEC 584-1, last revised in
1995, contains reference tables and calculation polynomials for the output signals of the standardized thermocouple types as a function of temperature.
THERMOCOUPLE DESIGN
Wire Sensors
In its simplest form, a thermocouple element consists of a
pair of wires that are connected together at a measuring
junction. The junction must be electrically conducting and
can be formed by soldering, crimping, or twisting the wires
together, depending on what the situation requires. Wire
sensors are mainly used to measure low temperatures
in favorable environments. One limitation is imposed by
the insulation material [e.g., poly(vinyl chloride) (PVC),
nylon, Kapton or poly(tetra fluoroethylene) (PTFE).
Another limitation is that the measuring junction is
exposed to the atmosphere. The PVC insulation can withstand temperatures up to 100 8C, whereas certain ceramic materials are tolerant of temperatures up to 1000 8C or
more.
Sheathed Thermocouples
In sheathed thermocouples, the wires are normally insulated by densely packed magnesium oxide enclosed in a
metal alloy suitable for the given thermocouple element.
THERMOCOUPLES
343
Thermal Shunting
A temperature sensor conducts heat, which gives what is
called thermal shunting. The problem is particularly
marked when the temperature is measured on pipes and
other surfaces. The greater the temperature difference,
the greater quantity of heat is drawn out of the body
by the sensor. There is a sharp drop in temperature at
the point where the sensor protrudes from the object to
be measured. This is caused by a load being imposed on
the object to be measured. The temperature drop is
greatest when the object to be measured is a poor conductor
of heat (low thermal conductivity). To overcome this
measurement problem, the point at which the sensor
leaves the body to be measured must be at a suitable
distance from the measuring junction.
Temperature Gradients and Thermal Conduction
Heat losses through the probe occur when a sensor connects a warm zone with a colder one, especially if the sensor
is the easiest path for the transfer of heat. Heat is conducted away from the object being measured to the probe.
The heat flux gives a temperature drop and the sensor
measures a lower temperature than the true value. Such
losses can be effectively countered if we ensure that the
thermal conductivity in the object and across the probe tip
is much higher than it is along the sensor. In other words,
more heat can be transferred to the sensor than conducted
away by the sensor sheath.
Response Time
Since the sensor only measures its own temperature, there
will almost always be a temperature deviation between the
temperature of the sensor and its surrounding. In theory,
the sensor temperature asymptotically approaches, but
never reaches, the surrounding temperature. For practical
purposes, the response time can be regarded as finite, but it
can be both negligibly small and cause severe measurement errors.
The response time is defined as the time needed for the
sensor to reach some fraction of a stepwise temperature
change of the surrounding, often 90% or 1(1/e) 67%.
However, the response time of a sensor must be accompanied by information about the conditions under which the
response time was obtained. The reason is that heat must
be transferred from the surroundings to the sensor. This
transfer takes some time, and the time needed differs
greatly between different conditions, such as still air and
stirred water. Too often, information of the conditions
associated with a particular response time are left out,
making the information useless. The response time is
connected to the sensor and its surrounding and not the
sensor itself.
Some critical factors affecting the response time of a
sensor in contact with a body or medium include the
following:
The heat capacity of the sensor. The greater heat capacity and mass, the longer response time.
344
THERMOCOUPLES
The heat transfer in the materials. Air gaps and insulation, for example, reduce the heat transfer.
The contact surface between the sensor and the body or
medium to be measured.
The response time can change over time; it can become
shorter if for example, the junction of a sheathed probe is
moved closer the sheath, or longer if, for example, a glue
become brittle and porous and thereby gets different heattransfer properties.
Self-Heating
Errors due to self-heating can be quite important in medical and biomedical applications depending on the small
sensors often required (9). Resistance-based sensors and
especially thermistors may be substantially affected by this
type of error, but thermocouples are not affected as they are
active sensors. All these types can, however, be affected by
EM interference (see the sections Electromagnetic Interference and Electromagnetic Aspects).
Material Defects and Ageing
Use of Alternative Sensor Materials. Some thermocouples are expensive and it can therefore be tempting to use
other materials as extension leads. As explained earlier,
however, the Seebeck effect is created throughout the
measuring circuit, so the use of other materials having a
different Seebeck coefficient can give rise to a faulty output
signal (7). There are materials, known as compensating
leads, that have the same electrical properties as the
thermocouple within limited temperature ranges, but it
is always better to use thermoelectric material throughout
the circuit. If this is not possible, compensating leads for
the type of thermocouple used must be employed.
Double Reversed Polarity. If the polarity of the extension lead has been reversed at both ends, the temperature
at the ends will affect the output signal. The reading will be
the temperature at the measuring junction less twice the
temperature difference between the terminal head and the
reference junction.
Electromagnetic Interference
Electromagnetic fields interact with materials inside the
field. Thermocouples and other measurement sensors
probes are no exception, and the frequent occurrence of EM
fields, especially in the medicalbiomecical engineering
sector, has contributed to many measurement errors.
The properties of an EM field change greatly with
frequency. Interaction with the field is highly dependent
on the geometry and the material of objects inside the
field, which together with the great frequency spectrum
of interest, makes evaluation of measurement interference
multifaceted and intricate. Thus it is very difficult to
predict and evaluate.
Measurement errors can arise due to direct effects, for
example, induced current in the thermocouple wires (10).
Remember that 1 8C corresponds to 50 mV for some typical thermocouples. Also, small currents can give significant
measurement errors. Induced currents can also heat the
wires and the measurement junction, leading to a too high
temperature reading. Indirect disturbances can arise, for
example, if the inserted probe disturbs the EM field. Such
indirect effects are not only associated with metallic
probesmaterial, but plastics as well (11).
THERMOCOUPLES
345
346
THERMOGRAPHY
BIBLIOGRAPHY
1. Doebelin EO. Measurement SystemsApplication and
design. 4th ed. New York: McGrawHill; 1990.
2. Cengel Y, Turner R. Fundamentals of Thermal-Fluid
Sciences. 2nd ed. New York: McGraw-Hill; 2005.
3. Holman JP. Heat Transfer. 9th ed. New York: McGraw-Hill;
2002.
4. Reed R. Manual on the Use of Thermocouples in Temperature
Measurement. American Society for Testing and Materials;
1993.
5. Dike PH. Thermoelectric Thermometry. Philadelphia: Leeds
and Northrup; 1954.
6. Moffat RJ. The gradient approach to thermocouple circuitry.
Temp Meas Control Sci 1962;3(2).
7. Pentronic AB (No date). Thermocouples. [Online]. Available
at http://www.pentronic.se/eng. Accessed 2005.
8. Omega Engineering Inc. (No date). Introduction to thermocouples. [Online]. Available at http://www.omega.com/techref/themointro.html. Accessed 2005.
9. Valvano JW, Nho S, Anderson GT. Analysis of the Weinbaum-Jiji model of blood flow in the canine kidney cortex for
self-heated thermistors. ASMEJ Biomech Eng 1994;116:
201207.
10. Chakraborty DP, Brezovich IA. Error sources affecting thermocouple thermometry in RF electromagnetic fields. J Microwave Power 1982;17(1):1728.
11. Chan KW, Chou CK, McDougall JA, Luk KH. Changes
in heating pattern due to perturbations by thermometer
probes at 915 and 434 mhz. Inter J Hyperther 1988;4(4):
447456.
12. Luechinger R, et al. In vivo heating of pacemaker leads
during magnetic resonance imaging. Eur Heart J
2005;26(4):376383.
13. Kaukuntla H, et al. Temperature monitoring during cardiopulmonary bypass-do we undercool or overheat the brain?
Eur J Cardiothor Surg 2004;26(3):580585.
14. Wangcun J, Aguilar G, Wang G, Nelson S. Heat-transfer
dynamics during cryogen spray cooling of substrate at
different initial temperatures. Phys Med Biol 2004;7
(49).
MONITORING; THERMOMETRY.
THERMOGRAPHY
HAIRONG QI
University of Tennessee
Knoxville, Tennessee
NICHOLAS A. DIAKIDES
Advanced Concepts Analysis, Inc.
Falls Church, Virginia
INTRODUCTION
The first documented application of infrared (IR) imaging
in medicine was in 1956 (1), when breast cancer patients
were examined for asymmetric hot spots and vascularity in
IR images of the breasts. Since then, numerous research
findings have been published (24) and the 1960s witnessed the first surge of medical application of the IR
technology (5,6), with breast cancer detection as the primary practice. However, IR imaging has not been widely
recognized in medicine nowadays, largely due to the premature use of the technology, the superficial understand-
THERMOGRAPHY
10 -4
10 -3
PATHOPHYSIOLOGICAL-BASED UNDERSTANDING OF
INFRARED IMAGING
Infrared imaging is a physiological test that measures the
subtle physiological changes that might be caused by many
conditions, for example, contusions, fractures, burns, carcinomas, lymphomas, melanomas, prostate cancer, dermatological diseases, rheumatoid arthritis, diabetes mellitus and
associated pathology, deep venous thrombosis (DVT), liver
disease, bacterial infections. These conditions are commonly
associated with regional vasodilation, hyperthermia, hyperperfusion, hypermetabolism, and hypervascularization
(19,2227), which generate higher temperature heat source.
Unlike imaging techniques, such as X-ray radiology and
Computed Tomography (CT) that primarily provide information on the anatomical structures, IR imaging provides
functional information not easily measured by other methods. Thus correct use of IR images requires in-depth physiological knowledge for its effective interpretation.
Human Thermal Models
The heat emanating on to the surface from the heat source
and the surrounding blood flow can be quantified using the
Microwave
Visible light
Gamma rays
Ultraviolet
10 -2
10 -1
10
Infrared
10 2
10 3
10 4
Radio
10 5
10 6
10 7
10 8
10 9
10 10
Wavelength (nm)
Near infrared
(NIR)
750
Short-wave
IR (SWIR)
1400
Mid-wave
IR (MWIR)
3000
347
Long-wave
IR (LWIR)
8000
12000
10 6 nm
348
THERMOGRAPHY
34.6
(36.3)
34.5
(35.8)
32.3
(33.9)
35.1
(37.2)
34.6
(36.3)
35.1
(37.2)
34.5
(35.8)
34.8
(37.1)
34.8
(37.0)
34.8
(37.0)
M2 (air)
H(x,y)
H(x)
H(x,y)
S
a
(1)
34.6
(37.1)
x
M1 (body)
32.3
(33.9)
R1
RS
US
C1
R2
C2
Rn
Cn
RA
UA
34.8
(36.7)
33.9
(35.1)
34.8
(36.7)
33.9
(35.1)
THERMOGRAPHY
349
350
THERMOGRAPHY
1980s, the Department of Defense (DoD) sponsored companies like Honeywell and Texas Instruments (TI) with
large classified contracts to develop uncooled IR detector
technology (45). Honeywells microbolometer and TIs pyroelectric sensors are both successful deliverables from these
programs. In 1999, the Defense Advanced Research Projects Agency (DARPA) issued a Broad Agency Announcement (BAA) (46) that solicits proposals for increasing the
performance of the uncooled IR sensors to their theoretical
limit. The objective for the thermal sensitivity is set at
<10 mk with the pixel size less than or equal to 25 mm. As
far as the array size, high performance arrays for longrange systems can be as large as 960 1280 elements,
while arrays for microsensors may be as small as
240 320 elements (46).
Compared to other uncooled IR detector technologies,
like ferroelectric and pyroelectric, microbolometer sensors
are less expensive, providing higher dynamic range,
broader spectral range, and lower cross-talk. Therefore,
this type of uncooled sensors are more popularly used,
especially after DoD declassified the microbolometer technology in 1992.
The microbolometer technology, which is thermalelectric in nature, converts IR energy to a change in resistance.
Each microbolometer detector consists of a silicon nitride
microbridge that lies above a silicon substrate and is
supported by silicon nitride legs, as shown in Fig. 5. A
bolometer is a thermal detector that is deposited on the
bridge. When heated by incoming radiation, the bolometer
detector can result in a temperature rise that is sensed as a
change in the element resistance.
Silicon nitride coated
with a thin film of bolometer
detector
Heat
Reflective layer
THERMOGRAPHY
351
352
THERMOGRAPHY
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1
1.5
2.5
3
3.5
Different features
4.5
THERMOGRAPHY
353
354
THERMOGRAPHY
BIBLIOGRAPHY
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guide to prognosis. Acta Unio Int Contra Cancrum 1962;
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3. Lawson RN, Chughtai MS. Breast cancer and body temperatures. Can Med Assoc J. 1963;88:6870.
4. Lloyd-Williams K, Handley RS. Infrared thermometry in the
diagnosis of breast disease. Lancet 1961; (2):13781381.
5. Gershen-Cohen J, Haberman J, Brueschke EE. Medical thermography: a summary of current status. Radiol Clin N Am
1965;3:403431.
6. Haberman J. The present status of mammary thermography.
Ca - A Cancer J Clin 1968;18:314321.
7. Keyserlingk JR, et al. Functional infrared imaging of the
breast. IEEE Eng Med Bio Mag MayJune 2000; pp. 3041.
8. Anbar M. Quantitative and dynamic telethermometrya
fresh look at clinical thermology. IEEE Eng Med Bio Mag
Jan.Feb. 1995;14(1):1516.
9. Head JF, Elliott RL. Infrared imaging: making progress in
fulfilling its medical promise. IEEE Eng Med Bio Mag Nov.
Dec. 2002;21(6):8085.
10. Head JF, Wang F, Lipari CA, Elliott RL. The important role
of infrared imaging in breast cancer. IEEE Eng Med Bio May/
June 2000; 5257.
11. Jones BF. A reappraisal of the use of infrared thermal image
analysis in medicine. IEEE Trans Med Imaging December
1998;17(6):10191027.
THERMOMETRY
37. Hay GA. Medical Image: Formation, Perception and Measurement. New York: America, The American Institute of
Physics and Wiley; 1976.
38. Watmough DJ. The role of thermographic imaging in breast
screening. discussion by C R Hill. Medical Images: Formation, perception and measurement 7th L H Gray Conference:
Medical Images. 1976; pp. 142158.
39. Gautherie M. Atlas of breast thermography with specific
guidelines for examination and interpretation. Milan. Italy:
PAPUSA; 1989.
40. Ng EYK, et al. Statistical analysis of healthy and malignant
breast thermography. J Med Eng Technol November/December 2001;25(6):253263.
41. Alexjander S, Deamer D. The infrared frequencies of DNA
bases: Science and art. IEEE Eng Med Bio Mag MarchApril
1999;18(2):7479.
42. Pavlidis I, Levine J. Thermal image analysis for polygraph
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43. Opgal Optronic Industries Ltd. FLIR cameras. Available at
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44. Opgal Optronic Industries Ltd. EYE Z640 cooled FLIR.
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45. Infrared Solutions. Historical facts of the microbolometer
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46. DARPA MTO Program. Baa99-30: Uncooled thermal imaging
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47. Bioyear, Inc. Prism 2000 thermal metabolic imaging system.
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48. Wiecek B. Advances in infrared technologyquantum well
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49. Infrared glossary of termsxenics. Available at http://
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51. Braunstein M, Chan RW, Levine RY. Simulation of dyeenhanced near-ir transillumination imaging of tumors. Proc
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52. Kaczmarek M, Nowakowski A. Analysis of transient thermal
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54. Head JF, Lipari CA, Elliott RL. Computerized image analysis
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infrared imaging system. Proc 1998 Conf Infrared Tech Appl
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59. Jakubowska T, Wiecek B, Wysocki M, Drews-Peszynski C.
Thermal signatures for breast cancer screening comparative
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Hassan M, et al. Infrared thermographic imaging for the
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Hassan M, et al. Non-invasive multi-modality technique to
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Harrison B, Mabuchi K. Biomedical infrared imaging in
Japan. IEEE Eng Med Bio Mag JulyAug 1998;17(4):6670.
Hassan M, et al. Noninvasive infrared imaging for quantitative assessment of tumor vasculature and response to
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2002;21(6):7379.
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MATTER.
THERMOMETRY
THEODOROS SAMARAS
Aristotle University of
Thessaloniki Department of
Physics
Thessaloniki, Greece
INTRODUCTION
High body temperature has been an indication of illness
since the time of Hippocrates, when only the hand could be
used to detect heat or cold. The development of thermometers as we know them was a slow process; it was not
before the late 19th century that thermometry became an
important tool in clinical practice (1). Medical thermometry is routinely used nowadays across the spectrum of
medical specialties and in all environments, ranging from
the home to the critical care unit. New techniques have
356
THERMOMETRY
THERMOMETRY
insulator
sheath
connection
leads
R2
RV
DVM
R3
RTD
357
RT R 0 e
358
THERMOMETRY
Conductor A
T2
T1
+
V
Conductor B
Measuring
junction
Secondary
junction
Conductor A
T1
Fiber-Optic Probes
Conductor C
Conductor B
Conductor C
T2
Thermocouple
Lead wires
Read-out
unit
The use of fiber-optic thermometers is necessary in situations, where electrical insulation for safety or electromagnetic immunity of the sensor is of concern. The most
common medical applications for which these requirements are of paramount importance are cancer treatment
with microwave or RF hyperthermia, temperature monitoring during Magnetic resonance imaging (MRI) and
cardiac output measurement with the thermodilution technique. There are mainly three reasons for which conventional thermoelectric devices (RTDs, thermistors or
thermocouples) should not be used inside electromagnetic
fields:
THERMOMETRY
359
1. The incident electromagnetic fields will be perturbed and scattered by the metal parts of the
thermometer devices.
2. Currents will flow in the metal parts of the devices,
resulting in their ohmic heating.
3. The currents in the devices can lead to spurious
readings.
Fiber-optic sensors work on the principles of light
absorption, reflection, scattering or interference, as well
as with the effect of induced fluorescence. With respect to
the implementation of the physical mechanisms, they
either operate in the time domain or they involve intensity
or wavelength modulation.
The simplest solution to temperature measurement
with a fiber-optic probe is the use of a gallium arsenide
(GaAs) crystal as the sensor. One implementation uses two
optical fibers, a transmitting and a receiving one. The light
transmitted by a light-emitting diode, after having been
partially absorbed in the GaAs sensor at the tip of the
probe, returns to the detecting module in the readout
equipment. It is known that some of the light energy that
gets absorbed in the crystal is used to raise electrons from
the valence band to the conduction band. As the energy gap
between the two bands is a known function of the crystals
temperature, the amount of absorbed power can be related
to the temperature of the GaAs sensor. A second implementation with semiconductor sensors uses the same crystal and a dielectric mirror (Fig. 4) at the end of a single
optical fiber and takes advantage of wavelength, instead of
intensity, modulation due to temperature variations. The
transmission spectrum of the crystal moves to larger wavelengths as its temperature rises (Fig. 5). This is known as
the absorption/transmission shift and occurs because the
energy of a photon is inversely proportional to its wavelength. When the temperature of the GaAs crystal
increases, reducing the energy gap between the semiconductors electron state bands, photons with less energy
(longer wavelengths) are absorbed, making the transmission spectrum shift toward higher wavelengths. The
advantages of this implementation include that the readout is independent of light intensity and, consequently,
factors, which usually contribute to the attenuation in
optical fibers, such as length, splices, and bending.
One of the first techniques that have been commercialized for fiber-optic probes is that of induced fluorescence.
This technique makes use of the change in fluorescence
decay time (lifetime) with temperature. At the tip of the
probe, a thermosensitive phosphor sensor is located. This
GaAs
crystal
Fiber
Sheath
Coating
Dielectric
mirror
sensor is stimulated by the red light of a pulsed lightemitting diode and emits light over a broad spectrum in
the near infrared region. The time needed for this fluorescence effect to decay depends on the temperature of the
phosphor sensor; the higher the temperature, the shorter
the decay time. The fluorescent signal continues to be
transmitted for some milliseconds through the same fiber
back to a detector in the readout equipment, even after the
stimulating light from the led is off. The fluorescent decay
time is then measured by a multipoint digital integration of
the decay curve. The use of the decay-time technique
eliminates the need to reference the output light intensity
to that incident on the sensor, a significant problem experienced in intensity modulation schemes.
Another approach to temperature measurement with
fiber-optic probes is FabryPerot interferometry, in which
two parallel, partially reflecting surfaces are brought very
close to each other to form an optical reflecting cavity, also
known as etalon. If the distance between these surfaces
(due to different coefficients of thermal expansion of the
materials they are made of) or the refractive index of the
material between them changes, the reflectance spectra
and the interference fringes change accordingly.
Apart from electromagnetic immunity, other advantages of fiber-optic probes include minimal thermal conduction along the probe and small size, down to 0.5 mm in
diameter. Their temperature range is very wide, their
accuracy can reach 0.1 8C, and their response time is in
the order of several hundred milliseconds.
MRI Thermometry
The use of minimally invasive surgery is very attractive
due to low costs and high effectiveness. It is usually conducted in the guidance of ultrasound imaging or MRI.
Thermal therapies combined with MRI have gained recognition in the recent years and include laser-induced thermotherapy (LITT), RF ablation, hyperthermia, and focused
ultrasound. In these techniques, it is not recommended to
use temperature sensors with metal parts, due to the
reasons described above. Instead, the signals collected to
reconstruct the image in the MRI devices can be used to
create temperature maps inside the patients in three
dimensions.
The effect of temperature on physical parameters measured by MRI devices has been known for a long time; the
first study on temperature measurement with such a
360
THERMOMETRY
M 0 1 et=T1
where a is the proportionality constant of linear temperature dependence of st, the value of which has been measured at approximately 0.01 ppm/8C (11). The main
advantage of the PRF method is its independence of tissue
composition. A potential artifact may arise from the presence of lipids, because the PRF of lipid hydrogen protons is
independent of temperature. Nevertheless, lipids can be
suppressed in gradient echo imaging by frequencyselective slice excitation. It is clear from equations 7 and
8 that the method is sensitive to changes in d B0 between
image acquisitions, due to drift of the external field, movement of the measured object, or change of magnetic susceptibility.
Comparisons among the three methods of MRI thermometry have shown that the PRF method is the one with
higher precision (12). An accuracy of 0.5 8C with an estimated resolution of 0.3 8C could be reached in a heterogeneous human phantom (13).
Radiation Thermometry
The random agitation of electrical loads or dipoles in
matter at a temperature above absolute zero is associated
with the generation of an electromagnetic wideband noise
signal with a spectrum extending from RF waves to
gamma rays. Infrared thermography, i.e., the recording
of the temperature distribution of the body using the IR
radiation emitted from its surface, and some millimeters
beneath it, exploits the wavelengths between 0.8 and
THERMOMETRY
2h f 3 D f dV
c2 exphkTf 1
361
c0
dtz
2a b dz
10
BIBLIOGRAPHY
1. Pearce JMS. A brief history of the clinical thermometer. QJM
Mon J Assoc Phys 2002;95:251252.
2. ISO/DGuide 99999, International vocabulary of basic and
general terms in metrology (VIM). 3rd ed. 2004
3. Preston-Thomas H. The International Temperature Scale of
1990 (ITS-90). Metrologia 1990;27:310.
362
TISSUE ABLATION
THERMOREGULATION.
THERMOTHERAPY.
See BIOHEAT
See HEAT
TRANSFER.
TISSUE ABLATION
DIETER HAEMMERICH
Medical University of
South Carolina,
Charleston, South Carolina
INTRODUCTION
Tissue ablation (literal translation removal) is the
destruction of diseased ( pathologic) body tissue, with the
aim to cure a disease. Tissue destruction is achieved by
thermal methods, or by application of chemical substances
(e.g., ethanol). Thermal methods cause either local heating
or cooling of the tissue to lethal temperatures (typically
below 40 8C, or above 50 8C). A number of different
physical principles are employed for heating and cooling
tissue, such as radio frequency (rf ) electric current, microwaves, laser, ultrasound, and cryogenic cooling.
Current clinical applications include treatment of heart
arrhythmia, cancer (liver, lung, brain, kidney, bone, prostate), uterine bleeding, varicose veins, and enlarged prostate (benign prostate hyperplasia), with other emerging
applications (see Table 1 for an overview). Typically,
an applicator is introduced under imaging guidance
[ultrasound imaging, fluoroscopy, computerized tomography (CT), magnet resonance imaging (MRI)] into the
body, to the treatment site. Then the tissue region around
the applicator is ablated, destroying the diseased tissue
area.
This article describes physical principles, clinical devices,
and applications of the different ablation modalities.
PHYSICAL PRINCIPLES OF TISSUE ABLATION
Thermal Ablation Methods
All thermal ablation methods rely on thermal conduction to
some extent to heat or cool a region of tissue near the
applicator. The problem of thermal ablation can mathematically be described by following heat-transfer equation:
rc
@T
r krT QA Qp
@t
Energy QA (Wm3) is applied to the tissue by the applicator, resulting in heating (or cooling) of the tissue. Some
energy Qp is carried away by blood perfusion; depending on
tissue type, perfusion may be negligible (e.g., heart), or
may have major impact (e.g., liver). The left-hand side of
equation 1 describes how local tissue temperature T
changes, depending on tissue density r and tissue specific
heat c. The first term on the right-hand side describes how
thermal energy is conducted through the tissue, depending
on thermal conductivity k. Different models are available
in the literature that approximate tissue perfusion, the
TISSUE ABLATION
363
rf
Cryo
Microwave
Cardiac ablation
Tumor ablation (liver, lung, kidney)
Endometrial
Prostate (cancer, enlarged prostate)
Intervertebral disk
Endovascular
Cornea
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
c
c
Ultrasound
Laser
Chemical
N/Ae
N/Ae
N/Ae
N/Ae
d
e
N/A
N/Ae
d
c
b
N/Ae
N/Ae
N/Ae
N/Ae
N/Ae
1
Blood perfusion
Conduction to
electrode
Joule
heat
Lesion
Myocardium
Electrode
Convective cooling
from blood
Blood
Catheter
body
Figure 1. Heat transfer during cardiac rf ablation. Tissue close to
the electrode is heated by resistive heating from rf current. Heat is
then conducted thermally into the tissue. Heat is lost due to blood
perfusion in the myocardium, due to thermal conduction through
the electrode, and from convective cooling due to blood flow in the
heart chamber. (From Ref. 2.)
s 2
1
jEj
jJj2
r
sr
364
TISSUE ABLATION
Advantages
Disadvantages
Radio frequency
Microwave
Ultrasound
Laser
Cryo
120
Impedance threshold
100
80
60
40
20
0
0
100
200
t (s)
300
400
TISSUE ABLATION
365
366
TISSUE ABLATION
zones to enable treatment of larger volumes. One successful method that has been applied to virtually all heat-based
methods is cooling the applicator (e.g., catheter). In all
catheter-based ablation methods, the highest SAR and
subsequently highest temperature is obtained close to
the catheter. In extreme cases, this can lead to tissue
carbonization, which should be avoided as discussed earlier. Applicator cooling is achieved by circulating cooled
water inside the catheter. Thereby, tissue close to the
catheter is cooled and carbonization is prevented. Furthermore, the location of highest tissue temperature is more
distant from the applicator (see Fig. 9). Since maximum
tissue temperature is limited (e.g., to 110 8C for rf ablation), this shift of maximum temperature results in an
increase of the size of coagulation zone. The radial dimension of the coagulation zone can be increased by up to a
factor of two when applicator cooling is used. Several
commercial devices employ applicator cooling.
Cryoablation (Cryotherapy, Cryosurgery). Cryoablation is historically older than other ablative methods,
and was introduced in the early 1960s (12). However, it
TISSUE ABLATION
367
through an orifice. The Joule Thompson effect can produce either heating or cooling, depending on the type of
gas, temperature, and pressure before expansion. For
cryoablation, argon is decompressed from 3000 psi
(21,000 kPa) to 150 psi (1000 kPa), resulting in cooling
down to 186 8C (the boiling temperature of argon).
Figure 11 shows a typical temperature distribution in
tissue surrounding a cryoprobe.
One advantage of cryoablation over heat based methods
is the visibility of the ice ball using ultrasound imaging
(14). The interface between the ice ball and surrounding
tissue is evident in ultrasound imaging (see Figure 12), and
allows real-time monitoring of the ablation procedure.
Chemical Ablation. During chemical ablation a cytotoxic agent is injected into the tissue site to be treated,
and diffuses into the tissue from the injection site. The
most commonly used agents are ethanol and acetic acid.
When ethanol is injected (ethanol ablation or percutaneous
ethanol injection) into tissue, it causes cell death by cell
dehydration, protein denaturation, and thrombosis of
small vessels. Acetic acid has the ability to dissolve lipids
100
90
80
No cooling
70
Cooling
T (C)
60
50
40
30
20
10
0
0
10
D (mm)
15
368
TISSUE ABLATION
Table 3. At Elevated Tissue Temperatures Different
Effects Take Place Depending on Temperature and Time
Temperature, 8C
3638
3842
>42
45
50
60100
>100
Tissue Effects
Normal physiological range
Fever
Elevated rates of enzyme activity, cell
death possible
Protein coagulation (after 12 h)
Protein coagulation (after 23 min)
Protein coagulation (instantaneous)
Tissue vaporization, carbonization
TISSUE ABLATION
369
Figure 13. Gross pathology of a coagulation zone created by rf ablation In vivo in porcine liver. Liver was
sliced right after the ablation procedure. The hyperemic
zone contains viable cells.
CEM43 R43Tt dt
5
Once CEM43 exceeds a certain critical value, the tissue can
be considered to be destroyed (i.e., ablated). The critical
value of CEM43 has been measured for many tissues, and is
340 min for liver; that is, tissue with t43 > 340 min can be
considered to be destroyed. Even though the relationship
stated in equation 5 may show inaccuracies in certain cases
(e.g., long application times), it is an accurate approximation for the time durations and temperatures that occur
during thermal ablation procedures.
Figure 14. Timetemperature relationship of cell death for different cell types. Note that all cell types exhibit the same exponential relationship (i.e., parallel lines), even though they have
different sensitivity (i.e., different times to cell death). (From Ref.
17.)
370
TISSUE ABLATION
Figure 15. Overview of rf ablation system for treatment of cardiac arrhytmia. An ablation catheter is
inserted through a leg vein, and steered into the heart
to the treatment site. The procedure is guided by X-ray
fluoroscopy. (From Ref. 22.)
RF generator
Ablation electrode
Catheter body
Procedure. The ablation and associated electrophysiology study are performed in a specially equipped laboratory.
The patient is either anesthetized or awake with sedation
to reduce discomfort and facilitate relaxation. Electrodes
and sensors attached to the patient report blood pressure,
blood oxygen saturation, and electrocardiogram (ECG).
Next, the locations where multiple diagnostic catheters
and the ablation catheter will be inserted (typically groin
and/or neck) are locally anesthetized. The catheters are
inserted into a blood vessel, and guided into the heart (see
Fig. 15). The physician performs mapping as described
below to determine the mechanism of the arrhythmia, and
site of ablation. The primary imaging modality used for
guidance is fluoroscopy, but other techniques are now used
to assist in both guidance and mapping, as described below.
The patient is typically discharged a few hours after the
procedure, but may be monitored in the hospital overnight.
Devices
Radio Frequency Ablation. Figure 16 shows a typical rf
ablation catheter tip with ablation electrode, and mapping
electrodes for measurement of biopotentials from the heart.
Most rf devices use temperature control, where power is
controlled to keep the temperature measured by a thermocouple or thermistor embedded in the catheter tip constant
(typically 6080 8C). Typical application times are 4560 s.
For treatment of atrial fibrillation, linear (i.e., elongated)
thermal lesions are required. Linear lesions can be created
by dragging or sequentially moving a standard catheter
(Fig. 16), but some special multielectrode catheters can be
TISSUE ABLATION
371
12.5
4.0
2.0
Catheter tubing
Sensing electrode
Temperature sensors
2 to 6 7F coil electrodes
Figure 17. Cardiac multielectrode catheter for creation of elongated (linear) thermal lesions. Each
electrode has two temperature sensors located near the edges for independent control. (From
Ref. 23.)
372
TISSUE ABLATION
Figure 21. Patient setup for liver tumor ablation. The ablation
catheter is inserted into the liver tumor through a small incision in
the skin. Ultrasound imaging is used for guiding the electrode into
the tumor, and monitoring the ablation. The white region in the
overlaid ultrasound image represents areas of gas bubbles due to
high temperatures. (From Ref. 28.)
TISSUE ABLATION
373
Figure 23. The rf electrodes of three manufacturers currently commercially available in the United
States, and in clinical use. Multiprong electrodes by RITA medical (a), and Boston Scientific (b).
Cooled needle electrode (single and triple cluster) by ValleyLab (c).
374
TISSUE ABLATION
Figure 24. Tumor (arrow) can be identified from this contrastenhanced CT image. Tumors are visible because they are typically
hypervascular (i.e., have higher density of blood vessels than
normal), and take up more of the contrast agent. (Image provided
courtesy of Bradford J. Wood, NIH.)
TISSUE ABLATION
375
coagulated areas anymore. Ultrasound imaging using contrast agents allows real-time monitoring of the ablation
procedure contrary to CT and MRI, which can typically
only be performed after the procedure.
Future Directions.
A continuing trend in tumor ablation is toward larger coagulation zones and shorter treatment times. High tumor recurrence rates close to large
vessels are still problematic, with improved applicators
attempting to address this issue. Adjuvant therapies
(e.g., radiation, chemotherapy agents) can kill cells at
lower elevated temperatures (above 45 8C) than heat
alone (above 50 8C). Thereby, the zone of cell death may
be extended (cf. Fig. 13), which may be beneficial close to large
vessels where it is difficult to achieve sufficient heating.
Unavailability of adequate monitoring of the extent of
the coagulation zone is a major problem for all heat-based
methods, especially when damage to nearby structures is
to be avoided. This problem is partially addressed by
ultrasound contrast agents as discussed above. Other
potential imaging solutions include thermometry, using
MRI or ultrasound imaging, and ultrasound elastography,
which allows imaging of the coagulation zone due to change
in elasticity after coagulation. Some companies are working on computer-assisted treatment planning systems that
guide the physician in optimal applicator placement, and
estimate coagulation zones.
Endometrial Ablation
Clinical Background. Ablation has become a standard
procedure for women with dysfunctional uterine bleeding,
with 30,000 annual procedures. Endometrial Ablation
(endometrium lining of the uterus) is indicated for
patients that do not respond to standard treatments like
drugs and curettage (scraping tissue from the endometrium with a spoon-shaped instrument). Initially either
laser or rf energy applied by a rollerball electrode was used;
the physician had to manually direct the catheter to ablate
the whole endometrium, which was time consuming. A
number of newer U.S. Food and Drug Administration
(FDA) approved devices that are more effective with
shorter treatment times are now available (32). These
second generation devices treat the whole lining at once,
and provide success rates of 6780%.
Devices.
There are currently five second generation
devices available on the U.S. market. Two devices use
heated fluid to ablate the endometrium. In one device,
heated saline (8090 8C) is circulated within the uterine
cavity for 8 min (Hydro Thermablator, Boston Scientific).
Another device employs a balloon catheter, inside which
heated Dextrose solution (5%) at 87 8C is circulated for
10 min (Thermachoice UBT, Gynecare). One device uses
cryoablation with a freezethaw cycle (10 min freezing) at
two locations in the uterine cavity (Her Choice, AMS). The
shortest treatment time is achieved by a device that uses
bipolar rf ablation employing mesh electrodes (Novasure,
Cytyc Corp.; see Fig. 26). The rf energy is applied for
90120 s, and controlled by tissue impedance. The last
device uses microwave ablation at 9.2 GHz, and 42 W
power for 3 min (MEA, Microsulis).
Prostate
Clinical Background.
Two types of prostate diseases
are prevalent in men. Prostate enlargement (Benign
prostate hyperplasia) is common in men >50 years of
age. The enlarged prostate imparts pressure on the urethra
resulting in restriction, at which point it has to be treated
to reduce prostate size. Cancer is the second common
disease affecting the prostate, and is the most common
form of cancer affecting men.
Current standard treatment options for enlarged prostate include medication, surgery where part of the prostate
is removed, and minimally invasive ablative methods. For
prostate cancer, treatment options are surgical removal
(radical prostatectomy) and external radiotheraphy. Ablative methods are currently only used in cases when conventional treatment fails, or in cases with advanced
disease to reduce tumor volume. Ablative treatment of
prostate cancer requires more precise control of the ablation zone than for enlarged prostate, since the cancer is
usually located in the periphery of the prostate (away from
the urethra) making treatment from inside the urethra
more difficult (33).
Commercial devices are available that employ cryo, rf,
microwave, and ultrasound. Depending on the device, the
prostate is treated by inserting the ablation catheter into
the urethra, rectum, or through the skin in the region
between the scrotum and anus (perineum). Urethra and
rectum have to be protected from damage by cooling when
heat-based devices are used, and by heating when cryoablation is used.
Devices for Enlarged Prostate Treatment
Microwave Ablation. Several devices are available that
use microwave antennas inserted through the urethra.
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Clinical Background.
Varicose veins are visibly
dilated and twisted veins near the skin surface, most often
affecting legs and thighs. Insufficiencies of the venous
valves result in blood pooling and enlargement of the veins.
Varicose veins affect 10% of the population, mostly
between ages 30 and 60.
Several treatment options are available, all aiming to
close the affected veins. Veins can be treated using surgical
stripping, sclerotherapy (injection of an agent that causes
vein swelling, and closure), and ablation. During treatment, a catheter is introduced into the vein and the vessel
wall is heated. The heat results in shrinkage of the collagen
in the wall, eventually closing off the vessel.
Devices
Radio Frequency Ablation. A bipolar, multielectrode
device (ClosurePlus, VNUS Medical) is commercially available (see Fig. 28) in two sizes (2 and 2.7 mm diameter). The
catheter is inserted into a vein and advanced to the treatment location. The rf energy is applied between two sets of
electrodes (2.7 mm catheter), or between outer electrodes
and inner ball electrode (2 mm catheter). Power is controlled so that vein wall temperature, as measured by a
thermocouple (located in the outer electrodes tips), reaches
85 8C. Heparinized saline is infused through the central
lumen of the catheter to prevent blood coagulation. Once
the target temperature is reached, the operator moves
the catheter at a rate of 23 cm per minute while keeping
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Company
Cardiac
Tumor
Endometrial
Prostate
Endovascular
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Table 4. (Continued )
Application
Company
Cornea
Intervertebral
DEVICE MANUFACTURERS
See Table 4.
BIBLIOGRAPHY
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2. Lai YC, et al. Lesion size estimator of cardiac radiofrequency
ablation at different common locations with different tip
temperatures. IEEE Trans Biomed Eng 2004;51:18591864.
3. Wright AS, Lee FT Jr, Mahvi DM. Hepatic microwave ablation with multiple antennae results in synergistically larger
zones of coagulation necrosis. Ann Surg Oncol 2003;10:275
283.
4. Labonte S, et al. Monopole antennas for microwave catheter
ablation. IEEE Trans Microw Theory 1996;44:18321840.
5. Saito K, et al. Heating characteristics of array applicator composed of two coaxial-slot antennas for microwave coagulation
therapy. IEEE Trans Microw Theory 2000;48:18001806.
6. Camart JC, et al. 915 MHz microwave interstitial hyperthermia. Part ii: Array of phase-monitored antennas. Int J
Hyperthermia 1993;9:445454.
7. Trembly BS, et al. Effect of phase modulation on the temperature distribution of a microwave hyperthermia antenna
array in vivo. Int J Hyperthermia 1995;10:691705.
8. Hynynen K, McDannold N. Mri guided and monitored
focused ultrasound thermal ablation methods: A review of
progress. Int J Hyperthermia 2004;20:725737.
9. Nau WH, Diederich CJ, Burdette EC. Evaluation of multielement catheter-cooled interstitial ultrasound applicators
for high-temperature thermal therapy. Med Phys
2001;28:15251534.
10. Diederich CJ, et al. Catheter-based ultrasound applicators for
selective thermal ablation: Progress towards mri-guided applications in prostate. Int J Hyperthermia 2004;20:739756.
11. Vogl TJ, et al. Mr-guided laser-induced thermotherapy (litt)
of liver tumours: Experimental and clinical data. Int J
Hyperthermia 2004;20:713724.
12. Gage AA. History of cryosurgery. Semin Surg Oncol 1998;14:
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13. Webster JG, editor. Minimally Invasive Medical Technology.
Bristol, UK: IOP Publishing; 2001.
14. Lee FT Jr, Mahvi DM, Chosy SG, Onik GM, Wong WS,
Littrup PJ, Scanlan KA. Hepatic cryosurgery with intraoperative us guidance. Radiology 1997;202:624632.
15. Miller MW, Ziskin MC. Biological consequences of hyperthermia. Ultrasound Med Biol 1989;15:707722.
16. Dewhirst MW, et al. Basic principles of thermal dosimetry
and thermal thresholds for tissue damage from hyperthermia. Int J Hyperthermia 2003;19:267294.
17. Sapareto SA, Dewey WC. Thermal dose determination in
cancer therapy. Int J Radiat Oncol Biol Phys 1984;10:787800.
18. Bischof JC, et al. Cryosurgery of dunning at-1 rat prostate
tumor: Thermal, biophysical, and viability response at the
cellular and tissue level. Cryobiology 1997;34:4269.
19. Weber SM, et al. Hepatic cryoablation: US monitoring of extent
of necrosis in normal pig liver. Radiology 1998;207:7377.
20. Zipes DP, Haissaguerre M. Catheter ablation of arrhythmias.
2nd ed. Armonk, NY: Futura Publishing; 2001.
21. Panescu D, Whayne JG, Fleischman SD, Mirotznik MS,
Swanson DK, Webster JG. Three-dimensional finite element
analysis of current density and temperature distributions
during radio-frequency ablation. IEEE Trans Biomed Eng
1995;42:879890.
22. Panescu D, Fleischman SD, Whayne JG, Swanson DK, Mirotznik MS, McRury I, Haines DE. Radiofrequency multielectrode catheter ablation in the atrium. Phys Med Biol
1999;44:899915.
23. Panescu D. Intraventricular electrogram mapping and radiofrequency cardiac ablation for ventricular tachycardia. Physiol Meas 1997;18:138.
24. Shpun S, et al. Guidance of radiofrequency endocardial ablation with real-time three-dimensional magnetic navigation
system. Circulation 1997;96:20162021.
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SURGERY.
TISSUE ENGINEERING
KRISTYN S. MASTERS
WILLIAM L. MURPHY
University of Wisconsin
Madison, Wisconsin
INTRODUCTION (14)
Definition
Tissue engineering represents a unique convergence of
work from the worlds of clinical medicine, engineering,
and basic science. The most commonly cited definition of
tissue engineering originates from an influential 1993
paper by Langer and Vacanti (1): Tissue engineering is
an interdisciplinary field that applies the principles of
engineering and the life sciences toward the development
of biological substitutes that restore, maintain, or improve
tissue function.
Although the term tissue engineering had existed for
several years prior to this 1993 publication, and the concept
of tissue engineering had existed for several decades, it is
Langer and Vacantis paper that is ultimately credited with
stimulating broad awareness and acceptance of this
description. This definition also served to unify seemingly
diverse lines of research, as it encompasses three general
strategies for the creation of new tissue, namely, the use of
isolated cells or cell substitutes; tissue-inducing substances; or cells placed on or within matrices.
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Figure 1. Depiction of three main tissue engineering strategies. In (a) cell transplantation, cells
are obtained from a donor (1), who is either the patient themselves, another person, or an animal,
then expanded in vitro (2), and reimplanted into the diseased/injured site (3), Regeneration via
scaffold alone is represented by (b), where a degradable, and possibly bioactive scaffold (1) may be
combined with inductive agents (2), and then implanted (3). Lastly, (c) depicts the implantation of
cell-seeded scaffolds, as cells are isolated from a donor (1), expanded in vitro (2), and combined with a
biomaterial scaffold (3), followed by either immediate implantation (4a) or further culture in an
in vitro bioreactor (4b) prior to implantation (5).
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Figure 7. Schematic representation of inductive tissue engineering approaches. Cells are exposed to 3D environments that are
engineered to contain covalently linked or soluble agents. The
agents are chosen to influence cell activity, ultimately leading to
induced growth of a desired tissue.
INDUCTIVE APPROACHES
A variety of investigators have designed 3D matrices to
interface directly with mammalian cells, and these materials were described in the biomaterials section above.
Both natural (e.g., collagen gels) and synthetic [e.g.,
poly(L-lactic acid)] materials have been used for decades
as scaffolding to support tissue formation from cells in vitro
or in vivo. These materials have historically been passive,
in that they have not exerted a high level of control over the
signals presented to resident cells. In the past decade,
matrices have been designed to interact with cells via
specific cell attachment ligands, or designed to deliver
soluble signals, so that characteristics of the cells microenvironment can be tightly controlled (Fig. 7). Bioactive
matrices have been used to delineate the effects of specific
cell attachment ligands, material properties (e.g.,
mechanics), and soluble signals on attachment, proliferation, migration, and differentiation of a wide variety of
mature cell types. These strategies are often termed
inductive approaches, as they are designed to induce a
particular cell activity (e.g., tissue formation). The following
paragraphs describe inductive schemes that have been used
to add a bioactive component to biomaterial matrices.
Covalent Modification of Biomaterials
One widespread approach used to confer bioactivity
involves covalently linking biologically active molecules
to a biomaterial (15). In this general approach, a biological
molecule is engineered to include a chemically reactive
group, which is then reacted with a functional group within
a biomaterial. The result is a material that has physical
properties defined by the original material, and with biological properties defined by the linked biological molecule.
This approach has been primarily used to link peptide
sequences that promote cell attachment, including RGDS,
RGDY, YIGSR, and IKVAV. For example, synthetic PEG
hydrogels and natural alginate hydrogels, which do not
intrinsically interact with cell surface receptors, can now
be readily modified with peptides that promote cell attachment and desired function. In addition to these methods
that deliver signals to cells, investigators have also developed materials that respond to cell activity. One example of
this general approach is materials that are held together,
or cross-linked, by biochemically labile chemistries. These
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389
Gene Delivery
Another set of inductive approaches does not rely on delivery of peptides or proteins to cells from a synthetic system,
but instead focuses on genetic manipulation of cell activity
(17). Investigators have developed a variety of strategies to
deliver genes to cells, and the genes are typically designed
to induce cells to secrete inductive proteins. The gene
delivery approaches often utilize the same core technologies that have been used for protein delivery, including
sustained release from polymer scaffolds and release from
hydrogel matrices, but they substitute plasmid DNA for
proteins. Plasmids are circular strands of DNA, which
typically contain a single gene under the control of a
promoter, which is chosen to enable production of an
encoded protein in the target cell type. The encoded protein, often a protein growth factor, is chosen to influence
cell activity. Therefore, this approach generates cells that
act as bioreactors to produce an inductive protein, and the
protein, in turn, encourages new tissue development. This
gene delivery approach has been successfully applied to
engineering of bone, skeletal muscle and vascular tissues,
and the general concept could find broad applicability in
engineering of essentially any tissue type.
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these cells were further characterized by Caplan and coworkers (see Ref. 5 for details) and called mesenchymal
stem cells (MSCs). The pioneering work of Caplans laboratory in skeletal tissue engineering using MSC sources,
coupled with a high profile publication by Pittenger et
al. (see Ref. 5 for details) describing the tremendous multipotential of these stem cells, has facilitated use of these
cells in bone tissue engineering applications. Recent studies have also identified other adult precursor cells that are
capable of forming bone tissue, including skin-, adipose-,
and dental pulp-derived mesenchymal stem cells. Investigators are now using each of these cell types as integral
components in bone tissue engineering schemes.
Biomaterials. Natural long bones (e.g., the femur)
develop upon a cartilage template matrix during a process
termed endochondral ossification. In many ways, this natural cartilage template serves as an ideal support for
development of new bone tissue. The cartilage matrix:
(1) is porous and therefore allows for infiltration of boneforming cells and vascular tissue; (2) is capable of withstanding the mechanical environment in an orthotopic
location; (3) provides a substrate that is conducive to
new bone formation; (4) is biodegradable and can be remodeled by infiltrating bone cells; and (5) contains signals
that induce new bone formation. These natural characteristics mirror the parameters that are important for design
of natural and synthetic scaffolds for bone tissue engineering, including pore structure, mechanical properties,
degradability, osteoconductivity, and osteoinductivity.
Osteoconductivity is generally defined as the ability of a
material to support formation of bone by bone-forming cells
(e.g., in a bone defect), while osteoinductivity is defined as
the ability of a material to induce formation of bone tissue
in conditions that are not otherwise conducive to bone
formation (e.g., in a nonorthotopic location). Investigators
have developed several classes of biomaterials to address
these parameters and to successfully engineer functional
bone tissue.
A broad range of natural and synthetic materials have
been explored in bone tissue engineering, including poly
(anhydrides), poly(fumarates), self-assembling peptide
amphiphiles, and alginate hydrogels. Although these
materials are well characterized in the context of bone
engineering, the most commonly used bone tissue engineering scaffolds have been poly (a-hydroxy esters), type I
collagen-based materials, and calcium phosphate based
minerals. Each of these base materials can be processed
into porous scaffolds that degrade into nontoxic byproducts, allowing for formation of new bone tissue in concert
with material degradation. In addition, the mechanical
properties of these matrices are dictated by their structure
and composition, allowing for significant mechanical tailoring. A particular advantage of calcium phosphate based
materials is a property known as bioactivity, which is the
ability of these materials to serve as an excellent template
for synthesis of mineralized tissue by bone cells and bone
precursor cells in vitro and in vivo. For example, mesenchymal stem cells differentiate and form bone tissue more
readily on calcium phosphate materials when compared
with other types of scaffold, including polyesters and
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protein-based hydrogels, and this phenomenon is attributed to calcium phosphate bioactivity. Many bone tissue
engineering approaches exploit this bioactivity by processing or synthesizing new types of calcium phosphate based
materials, including both natural (e.g., coralline hydroxyapatite) and synthetic (e.g., sintered hydroxyapatite) scaffolds. Recent approaches have also combined natural and
synthetic polymers with calcium phosphate minerals to
create hybrid materials for bone tissue engineering. These
materials directly mimic the organicinorganic composite
structure of the natural bone extracellular matrix, and
they have shown substantial promise as supportive scaffolds for new bone formation.
Bioreactors. In vitro engineering of bone tissue has
been an active area of study for over a decade. However,
early attempts at bone tissue engineering demonstrated
limitations that highlight the importance of bioreactor
design. Previous studies indicate that growth of bone tissue
within 3D scaffolds in static culture conditions is limited to
the outer 200800 mm of a scaffold construct. The poor
tissue growth and cell death observed at locations deeper
within these scaffolds was likely caused by poor nutrient
transport into the developing tissue. These studies and
others have provided an impetus to create new bioreactor
systems that enhance mass transport and allow for development of more homogeneous bone tissue in vitro. Spinner
flasks and rotating wall bioreactors have been shown to
substantially enhance bone synthesis by mesenchymal
stem cells cultured within 3D polyester scaffolds. In addition, perfusion culture systems successfully enhanced generation of bone tissue by osteoblasts and bone marrowderived precursor cells in vitro. In each case, the success of
these approaches is attributed to improved nutrient transport within the developing tissue, which is generated by
fluid flow.
Other in vitro bioreactors have been designed to understand and manipulate the effect of mechanics on engineered bone tissue growth. Mechanical forces have a
well-known influence on remodeling of adult bone tissue
and, in turn, regulation of bone strength over time.
Mechanical stimulation is also vital to proper early development of cartilage and bone, and the mechanical properties of developed bone tissue can be correlated to the load
applied during development. In view of these mechanical
effects on bone maintenance and development, it is not
surprising that mechanical forces have a pronounced effect
on bone formation by osteoblasts and osteoblast precursor
cells in cell and tissue culture. Culture systems that apply
compressive or shear forces to bone-forming cells have
shown that the cells respond to mechanical stress by
enhancing synthesis of bone matrix.
Inductive Approaches. It is clear that protein growth
factors are a vital component of natural bone development
and repair processes, due to their effects on bone forming
cells and blood vessel ingrowth. Based on these observations, investigators are developing several novel delivery
systems that allow for controlled delivery of protein growth
factors to bone defect sites to improve or accelerate bone
healing. The most potent known growth factors related to
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durable, nonobstructive, nonthrombotic, self-repairing tissue valve that would grow with the patient and remodel in
response to in vivo stimuli is the current goal for tissue
engineered heart valves.
Cell Sources. The source of cells to use in valve regeneration remains a significant concern. Valvular interstitial
cells (VICs) comprise the majority of the cell population in
heart valves, with a thin layer of endothelial cells (ECs)
providing the valve with a nonthrombogenic surface. The
adaptive, complex, and dynamic structure of heart valves
can be primarily attributed to the VICs, which are responsible for valve extracellular matrix production as they
constantly remodel and repair the valve. The organization
and relative proportions of the valve matrix are paramount
to valve function, thus emphasizing the importance of
these interstitial cells. Although these cells readily proliferate and function in in vitro culture, they are very difficult
to obtain from a patient or living donor. Other mature cell
types, such as smooth muscle cells, dermal fibroblasts, and
myofibroblasts, can perform some of the functions of
VICs, but ultimately do not exactly mimic all of the properties of VICs. Recent studies suggest that marrow stromal
cells may be a viable immature cell source for valve
tissue engineering. Embryonic stem cells also hold
promise as a cell source for VICs, although the method
of inducing their differentiation to VICs has not yet been
identified.
Construction of fully functional heart valves will also
require endothelialization of the valve surface. The ECs
play a critical role in both the maintenance of valve homeostasis and the pathogenesis of valvular disease. Mature
cell sources for ECs include dermal microvascular endothelial cells (HDMECs), which are isolated from human foreskin, and endothelial cells isolated from human umbilical
veins (HUVECs). However, neither of these sources provide autologous cells for a patient in need of valve replacement. Mesenchymal stem cells have recently been shown to
differentiate into ECs, indicating that MSCs are a promising source for autologous ECs. Researchers have also
identified techniques to induce the differentiation of ECs
from embryonic stem cells.
Biomaterials. Construction of a tissue engineered heart
valve requires a material that is readily processed into a
complex shape, can withstand harsh hemodynamic stresses, and yet is flexible enough to allow for valve opening
and closure. To this end, synthetic scaffolds have been
constructed using PGA, PLGA, polyhydroxyalkanoate
(PHA), or poly-4-hydroxybutyrate (P4HB). Studies using
PGA/P4HB in particular have been very successful in large
animal models. Much work has also focused upon using
decellularized native valves as a scaffold material; in this
approach, immunogenicity of a donor valve is lessened by
removing the cells, leaving only the extracellular matrix
structure. The primary advantage of this strategy is that
the appropriate matrix composition of the valve is already
present and does not have to be reconstructed. These valve
scaffolds can then be recellularized with autologous (nonimmogenic) cells, with the goal of restoring the valves
regenerative capacity. Finally, hydrogels made from
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5. Lanza R, et al., editors. Handbook of Stem Cells. Volumes 1
and 2. New York: Elsevier Academic Press; 2004.
6. Zandstra PW, Nagy A. Stem cell bioengineering. Ann Rev
Biomed Eng 2001;3:275305.
7. Li L, Xie T. Stem cell niche: structure and function. Ann Rev
Cell Dev Biol 2005;21:605631.
8. Yannas IV. Natural materials. In: Ratner BD, Hoffman AS,
Schoen FJ, Lemons JE, editors. Biomaterials Science. New
York: Elsevier Academic Press; 1996.
9. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem
Rev 2001;101:18691879.
10. Baier Leach J, et al., editors. Encyclopedia of Biomaterials and
Biomedical Engineering. New York: Marcel Dekker; 2004.
11. Cannizzaro S, Langer R. Biomaterials: Synthetic and engineering strategies. In: Dillow AK, Lowman AM, editors.
Biomimetic Materials and Design: Biointerfacial Strategies,
Tissue Engineering and Targeted Drug Delivery. New York:
Marcel Dekker; 2002.
12. Thomson RC, Ishaug SL, Mikos AG, Langer R. Polymers for
biological systems In: Meyers RA, editor. Encyclopedia of
Molecular Biology: Fundamentals and Applications. New
York: VCH Publishers; 1996.
13. Ratcliffe A, Niklason LE, Bioreactors and bioprocessing for
tissue engineering. Ann NY Acad Sci 2002;961:210215.
14. Martin I, Wendt D, Heberer M. The role of bioreactors in
tissue engineering. Trends Biotechnol 2004;22:8086.
15. Lutolf MP, Hubbell JA. Synthetic biomaterials as instructive
extracellular microenvironments for morphogenesis in tissue
engineering. Nat Biotechnol 2005;23:4755.
16. Saltzman WM, Olbricht WL. Building drug delivery into
tissue engineering. Nat Rev Drug Discov 2002;1:177186.
17. Bonadio J, Goldstein SA, Levy RJ. Gene therapy for tissue
repair and regeneration. Adv Drug Del Rev 1998;33:5369.
18. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering:
State of the art and future trends. Macromol Biosci 2004;4:
743765.
19. Jadlowiec JA, Celil AB, Hollinger JO. Bone tissue engineering: Recent advances and promising therapeutic agents. Exp
Opin Biol Ther 2003;3:409423.
20. Green D, Walsh D, Mann S, Oreffo ROC. The potential of
biomimesis in bone tissue engineering: Lessons from the
design and synthesis of invertebrate skeletons. Bone
2002;30:810 815.
21. Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules
for myocardial tissue engineering. Pharmacol Ther
2005;105:151163.
22. Masters KS, Mann BK. Tissue engineered heart. In: Nedovic
V, Willaert R, editors. Applications of Cell Immobilisation
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TIMOTHY HOLMES
St. Agnes Cancer Center
Baltimore, Maryland
THOMAS R. MACKIE
University of Wisconsin
Madison, Wisconsin
INTRODUCTION
Tomotherapy is intensity-modulated rotational radiotherapy utilizing a photon fan beam (1). The term tomotherapy
derives from tomographic radiotherapy, literally meaning
slice radiotherapy. Tomotherapy treatment delivery is
conceptually similar to computerized tomographic (CT)
imaging where a three-dimensional (3D) image volume
is acquired as a stack of two-dimensional (2D) crosssectional images. By analogy, a tumor volume can be
subdivided into a stack of slices that are independently
irradiated to achieve a 3D conformal dose distribution.
Dose conformation is achieved by modulating the intensity
pattern of the incident X-ray beam during rotation of the
X-ray source using a fan-beam multileaf (MLC) collimator
whose leaves are pneumatically driven to achieve near
instantaneous leaf transitions between open and closed
states. As shown in Fig. 1, the table motion can be incrementally stepped the width of the fan beam after each
completed arc (serial tomotherapy) (2,3) or it can be
RADIOLOGY.
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(b)
(a)
(a)
(b)
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optimization, the intensity levels are discretized for treatment delivery, with 50 levels chosen to reduce the uncertainty in the target dose due to intensity discretization to
<0.1%. Discretization of couch travel is determined by the
pitch ratio: the ratio of the couch travel distance per
rotation to the field width defined at the axis. In helical
tomotherapy delivery, the pitch is usually set to be less
than one-half to avoid thread-like dose artifacts developing
near the edge of the field becoming clinically significant
(17). Given a typical pitch of 0.3 for a 25 mm field width, the
table motion is modeled by offsetting adjacent beams by
0.147 mm (e.g., 0.3 25 mm/51) increments parallel to the
direction of table motion.
A Hi-ART II treatment delivery typically takes <5 min
for small target volumes like a prostate and <10 min for
larger volumes such as head and neck. Mackie et al. (19)
provided an expression for estimating the irradiation time
given the target length L, the beam width W, the prescribed
dose D, the average dose rate at the target R, and the
modulation factor M:
T MDL W=WR
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Figure 5. Verification CT at megavoltage (MV) energies of a RMI Solid Water CT phantom. The 3%
contrast plug is clearly seen as are the 1.2 mm and 1.6 mm air holes in the solid water phantom. The
dose was estimated at 3 cGy at the center of the phantom.
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Tumor
Figure 6. Verification CT of a lung patient. The panel on the left
is a soft-tissue window and the panel on the right is a lung window.
The difference between muscle and fat and bone and soft tissue is
clearly distinguishable. Some of the vascular structures are visible
in the lung. The tumor boundary in the lung is discernable, but its
extension into the mediastinum is not visible. The dose to the
patient was 3 cGy.
bladder are visible. Unlike the highest quality conventional CT scanners, the contrast between white and gray
matter in brain is not visible.
The CT imaging is performed prior to each treatment to
reduce the possibility of a geometrical miss of the target
and sensitive structures. An automated comparison of
verification and planning image sets is carried out immediately following image acquisition to guide the adjustment
of the patient setup. The patient is assumed to be a rigid
object requiring translations and rotations to bring the
target anatomy and important sensitive structures into
alignment with the treatment plan. The patient is positioned by aligning the patients skin marks with lasers
located outside of the bore of the unit. A sagittal representation of the patients planning CT is shown on the operator
console to aid in selecting the slices to be scanned. A
verification scan is taken and reconstructed during the
acquisition. The patient is then transported to the same
position outside of the gantry bore while the verification
image set is fused onto the planning image set and the
translation and rotation offsets are reported. Typically the
image fusion is first done automatically using a mutual
information algorithm (21). Following automated registration, the patient registration can be fine-tuned manually.
This allows the operator to take into account, as best as
possible, the nonrigid nature of the transformation. Once
Figure 7. The registration window for a prostate patient. The gray squares are from the planning
CT. The verification CT is shown in the upper left and the planning CT is in the lower left. The yellow
squares in the large panel are from the tomotherapy verification CT. The rectal boundary and the fat
pad surrounding the prostate are clearly aligned on these transverse images. Note that the skin
boundary and the leg bones are not as well aligned as the prostate. Regions of interest and the dose
distribution obtained from the planning system can be superimposed on the images, but these
capabilities have been turned off in this presentation. The translational alignments suggested were
0.0 mm lateral, 0.6 mm longitudinal, and 1.5 mm vertical.
TOMOTHERAPY
401
402
TONOMETRY, ARTERIAL
TONOMETRY, ARTERIAL
JOSEPH S. ECKERLE
SRI International
Menlo Park, California
INTRODUCTION
The arterial tonometer is an instrument for measuring
arterial blood pressure. It differs from the familiar sphygmomanometer in that, rather than measuring the pressure
only at greatest contraction and greatest heart dilation
(systolic and diastolic), it provides continuous measurement throughout the hearts pumping cycle. Typically, the
instrument sensor is placed over a superficial artery;
the radial artery pulse point at the wrist is one convenient
site for tonometer measurements. Figure 1 shows how a
tonometer sensor would be placed for measurements at
this site.
A catheter can be used for accurate, continuous measurement of blood pressure, but the instrument is invasive
and numerous risks are associated with its use. In contrast,
the noninvasive tonometer can provide an accurate, continuous blood pressure measurement with negligible risk.
Sphygmomanometric instruments of several types are
available for noninvasive blood pressure measurements.
However, these instruments are generally not capable of
continuous blood pressure measurement, nor is their longterm use feasible. The familiar blood pressure cuff hinders
venous return and results in peripheral edema. In contrast
to sphygmomanometric instruments, the tonometer can be
used for beat-by-beat blood pressure measurement over
long periods of time with minimal edema. Important disadvantages of the tonometer include its sensitivity to
sensor placement and movement artifacts, effects of anatomical variations, and the greater complexity and cost
relative to a conventional sphygmomanometer.
In what follows, the physical principles that form the
theoretical basis for tonometric blood pressure measurement are first presented; these include techniques for
identifying the location of an artery beneath a tonometer
sensor and for adjusting the force with which the sensor is
PRINCIPLES OF OPERATION
General Principles
The fundamental principles underlying arterial tonometry
are similar to those for ocular tonometry (1,2). Figure 2
shows an idealized model that helps illustrate these principles. In Figure 2, P represents the blood pressure in a
superficial artery and F is the force measured by a tonometer transducer. The membrane is the artery wall.
Figure 2b is a free body diagram showing all the forces
and moments acting on the frictionless piston of Fig. 2a. As
shown in Fig. 2b, an ideal membrane transmits only a
tensile force, T, and does not transmit any bending
moment. The tension vector shown, T, is perpendicular
to the pressure vector, so the force, F, is independent of T
and depends only on the blood pressure and the area of the
frictionless piston, A. Following common practice, the integrated effect of arterial pressure acting on the segment of
arterial wall is represented by a vector of magnitude PA,
oriented perpendicular to the wall. Thus, measurement of
the force, F, permits one to directly infer the intraarterial
pressure.
Figure 3 shows a superficial artery and a tonometer
sensor in cross-section. The tonometer sensor is represented schematically, and is modeled as an assemblage
of springs with spring constants, K, as shown. By careful
design of the tonometer sensor and selection of an appropriate superficial artery, it is possible to satisfy several
conditions:
TONOMETRY, ARTERIAL
403
404
TONOMETRY, ARTERIAL
Hold-Down Force
TONOMETRY, ARTERIAL
405
406
TONOMETRY, ARTERIAL
Ref. 26
Ref. 9
Units
8
0.75
25
3
0.25
1
1 (estimate)
>50
<0.5
31
0.2
2550
n.r.
n.r.
n.r.
n.r.
n.r.
n.r.
Each
mm
mV/V mmHg
mmHg
%8C1
mmHg8C1
mmHg
Hz
mmHg
MISCELLANEOUS CONSIDERATIONS
One significant advantage of the arterial tonometer is its
ability to make noninvasive, nonpainful, continuous measurements for long periods of time. There are several
reasons for this superiority over the sphygmomanometer:
1. The sensor is adjusted to partly flatten, but not
occlude the radial artery. In contrast, sphygmomanometric systems typically occlude the artery in
order to determine systolic pressure.
TONOMETRY, ARTERIAL
407
APPLICATIONS
Perhaps the first clinical application of tonometry was for
blood pressure monitoring in surgery and other procedures. Stein and Blick (23) used radial artery tonometry
during a catheterization procedure. Kemmotsu et al. (39)
used a multiple-element tonometer for surgical monitoring. Several others (4043,55) have also evaluated the
instrument under various surgical and postsurgical situations.
Figure 10 shows a typical blood pressure waveform,
obtained with an arterial tonometer from the radial artery
of an adult male. Note that systolic and diastolic pressures,
as well as pulse rate and dicrotic notch information, can be
obtained from the waveform. The subject performed a
Valsalva maneuver at the time indicated. The attendant
changes in blood pressure and pulse rate are quite clearly
indicated. Of course the tonometer measures only the
pressure in the underlying artery, not central arterial
408
TONOMETRY, ARTERIAL
MEASUREMENT ACCURACY
Because the accuracy of tonometric blood pressure
measurements depends on the size and positioning of
the sensor, the value of hold-down force, and the accuracy of the sensor itself, some variability in reported
tonometer accuracy can be expected when these factors
are not well controlled. In nearly all of the measurements reported prior to 1987 hold-down force was
adjusted manually, and in many the tonometer was
manually positioned as well. Some improvement in
tonometer accuracy and repeatability can be expected
from automatic sensor positioning and hold-down force
adjustment.
An early validation of the principles of tonometry (60)
involved comparison of pressures measured in an exposed
canine femoral artery by both a tonometer and an intraarterial catheter. One series of tests involved 15 animals with
blood pressure changes being induced by drug injection
and vagal stimulation. For this entire series of tests, the
difference between pressures measured by the two instruments was never > 5%.
Stein and Blick (23) compared tonometric measurements with direct arterial blood pressures on 20 patients
undergoing cardiac catheterization. They found that the
tonometer reproduced both the intraarterial waveform and
any abrupt changes in pressure caused by various interventions with remarkable fidelity. Specifically, during
interventions that increased or decreased systolic pressures by as much as 30%, the tonometric pressure measurement followed the direct arterial pressure within 10%
in 92% of the observations.
Weaver et al. (8) compared sphygmomanometric blood
pressures with those obtained with a multiple-element
tonometer sensor on five subjects of both sexes ranging
in weight from 135 to 225 lb (61102 kg). The standard
deviation between the two measurements of systolic and
diastolic pressures was 6.5 mmHg (870 Pa), indicating that
the tonometer was at least as accurate as the sphygmomanometer.
In 1989, Kemmotsu et al. (39) reported the accuracy of
an automated, multiple-element tonometer instrument
used for monitoring during surgery. The tonometric measurements showed good correlation (r 0.94, P <0.001 for
systolic) with invasive measurements on the contralateral
radial artery. Kemmotsu subsequently performed additional studies (40,41) involving surgical monitoring.
In the later study (41), involving 60 patients, the mean
absolute value of error ranged from 3.6 to 6.6 mmHg (480 to
880 Pa). Standard deviations ranged from 4.5 to 6.2 mmHg
(600 to 830 Pa).
Other investigators (42,43,55) have evaluated multipleelement tonometers for surgical and postsurgical monitoring. They found standard deviations ranging from 1.7 (for a
single patient) to 14.2 mmHg (230 to 1960 Pa).
Sato et al. (61) evaluated the accuracy of a multipleelement tonometer instrument on conscious subjects subjected to a Valsalva maneuver and a tilting test. This study
is of particular interest because they directly addressed the
question of frequency response of the tonometer/tissue/
artery system. Good frequency response is important for
computation of windkessel parameters or PWV as
described above. Sato et al. found the frequency response
of the tonometer/patient system to be essentially flat from
0 to 5 Hz.
TONOMETRY, ARTERIAL
BIBLIOGRAPHY
1. Mackay RS, Marg E. Fast, automatic electronic tonometers
based on an exact theory. Acto Ophthalml 1959;37:495
507.
2. Mackay RS. Fast automatic ocular pressure measurement
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3. Pressman G, Newgard P. A transducer for the continuous
external measurement of arterial blood pressure. IEEE Trans
Bio-Med Electron 1963;BME-10:7381.
4. Drzewiecki GM, Melbin J, Noordergraaf A. Arterial tonometry: Review and analysis. J Biomech 1983;16:141152.
5. Drzewiecki GM, Melbin J, Noordergraaf A. Deformational
forces in arterial tonometry. Proc Annu Conf IEEE/Eng Med
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6. Kelly R, Hayward C, Avolio A, ORourke M. Noninvasive
determination of age-related changes in the human arterial
pulse. Circulation 1989;80:16521659.
7. Eckerle JS, Newgard PM, A non-invasive transducer for the
continuous measurement of arterial blood pressure. Proc
Annu Conf Eng Med Biol 1976;29:98.
8. Weaver CS, et al. A study of non-invasive blood pressure
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1978;167:89105. Prepared for a conference sponsored by
NASA Office of Technology Utilization and Cardiology Division, Stanford University School of Medicine. Society of Photo
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9. Terry S, Eckerle JS, Kornbluh RD, Ablow CM. Silicon pressure transducer arrays for blood-pressure measurement.
Sensors Actuators 1990;A 21A 23:10701079.
10. Eckerle JS. Noninvasive blood pressure monitoring transducer. US Patent 4,269,193. 1981.
11. Niwa M. Pulse wave detecting apparatus. US patent
5,103,831. 1992.
12. Kobayashi I. Pulse wave detecting apparatus. US patent
5,170,796. 1992.
13. Takaya M. Continuous blood-pressure monitor apparatus.
US patent 6,394,959 B1. 2002.
14. Shinoda M, Ogletree WA. Pulse wave detecting apparatus.
US patent 4,784,152. 1988.
15. Kaida N, et al. Pulse wave detecting apparatus. US patent
4,901,733. 1990.
16. Eckerle JS. SRI Tonometer Blood Pressure Measurement
System, Operators Instruction Manual. Final Rep., SRI Proj.
No. 4908, Washington (DC): Lab. Div., Federal Bureau of
Investigation; 1984.
17. Petzke JC, Bahr DE. Blood pressure measuring apparatus.
US patent 3,926,179. 1975 Dec 16.
18. Eckerle JS. Blood pressure monitoring method and apparatus. US patent 4,799,491. 1989.
19. Niwa M. Pulse wave detecting apparatus. US patent
5,119,822. 1992.
20. Ohmori K, Narimatsu K, Kobayashi I. Blood pressure monitoring apparatus. US patent 5,590,661. 1997.
21. Eckerle JS, Fredrick J, Jeuck P. Toward a practical tonometric blood pressure instrument. In: Semmlow JL, Welkowitz W, editors. Proceedings of the Annual Confrence LEEE/
English Medical Biology Society 6th; 1984. p. 635641.
22. Bigliano RP, Molner SF, Sweeney LM. A new physiological
pressure sensor. Proc Ann Conf Eng Med Biol 1964;6:82.
23. Stein PD, Blick EF. Arterial tonometry for the atraumatic
measurement of arterial blood pressure. J Appl-Physiol
1971;30:593596.
24. Bahr DE, Petzke JC. The automatic arterial tonometer. Proc
Annu Conf Eng Med Biol 1973;15:259.
409
25. Borkat FR, Kataoka RW, Silva J. An approach to the continuous non-invasive measurement of blood pressure. Proceeding of the San Diego Biomedical Symposium; 1976.
26. Weaver CS, et al. 1976: Wearable Blood Pressure and ECG
Recording System. (Grant HL 17604-01A1), Interim Report
to the National Heart and Lung Institute, Bethesda (MD);
1976.
27. Drzewiecki GM, Butterfield RD, and Ciaccio EJ, Pressure
waveform monitor. US patent 5,363,855. 1994.
28. Guckel H, Burns DW. Planar processed polysilicon sealed
cavities for pressure transducer arrays. Proc IEEE Int Electron Devices Meet 1984.
29. Corcuera M, Aravamudhan S, Bhansali S. (No Date). A noninvasive microsystem for blood pressure measurement,
Research Experience for Undergraduates, Spring 2004 Symposium, Poster No. EE.3. University of South Florida.
[Online]. Available at www.eng.usf.edu/schlaf/REU/Symposium/Spring2004/Corcuera2004.pdf Accessed 2005April 8.
30. Fujikawa K, Harada C. Semiconductor pressure pulse wave
system. US patent 5,101,829. 1992.
31. Harada C, et al. Contact pressure sensor. US patent
5,179,956. 1993.
32. Narimatsu K, Kawamura N. Pressure wave sensor. US
patent 5,467,771. 1995.
33. Eckerle JS, et al. Cardiovascular Activity Monitoring for
Polygraph Examination, SRI Final Rep., Contract J-FBI82-108, Washington (DC): Federal Bureau of Investigation;
1984.
34. Eckerle JS, The arterial tonometer: A non-invasive blood
pressure instrument for trauma victims. Non-Invasive Neurologic Evaluation of the Combat Casualty Victim, Bethesda
(MD) Naval Medical Research and Development Command;
1985.
35. Eckerle JS, et al. Pulse rate sensor system. US patent
5,243,992. 1993.
36. Shinoda M, Lippincott HW. Continuous blood pressure monitoring system having a digital cuff calibration system and
method. US patent 5,165,416. 1992.
37. Aung Y, Takaya M, Nishibayashi H. Blood pressure monitor
system. US patent 5,261,414. 1993.
38. Kawamura N, Nakagawa T, Aung Y. Blood pressure monitor
system. US patent 5,279,303. 1994.
39. Kemmotsu O, et al. A non-invasive blood pressure monitor
based on arterial tonometry. Anesthes Analges (Suppl.)
1989;68:S145.
40. Kemmotsu O, et al. Blood pressure measurement by arterial
tonometry in controlled hypotension. Anesthes Analges 1991;
73:5458.
41. Kemmotsu O, et al. Arterial tonometry for non-invasive,
continuous blood pressure monitoring during anesthesia.
Anesthesiology 1991;75(2):333340.
42. Searle NR, Perrault J, Ste-Marie H, Dupont C. Assessment of
the arterial tonometer (N-CAT) for the continuous blood
pressure monitoring in atrial fibrillation. Can J Anaesthesiol
1993;40(4):388393.
43. Siegel LC, Brock-Utne JG, Brodsky JB. Comparison of arterial tonometry with radial artery catheter measurements of
blood pressure in anesthetized patients. Anesthesiology
1994;81(3): 578584.
44. Chen C, et al. Estimation of central aortic pressure waveform
by mathematical transformation of radial tonometry pressure validation of generalized transfer function. Circulation
1997; 95:18271836.
45. Narimatsu K, Takatani S, Ohmori K. A multi-element carotid
tonometry sensor for non-invasive measurement of
pulse wave velocity. Frontiers Med Biol Eng 2001;11(1):45
58.
410
Further Reading
Geddes LA. The Direct and Indirect Measurement of Blood Pressure. Chicago: Year Book Medical Publishers, Inc.; 1970.
ORourke MF, Kelly RP, Avolio AP. The Arterial Pulse. London:
Lea & Febiger; 1992.
Nichols WF, ORourke MF, Hartley C. McDonalds Blood Flow in
Arteries. 4th ed. New York: Oxford University Press; 1998.
See also BLOOD PRESSURE MEASUREMENT; IMPEDANCE PLETHYSMOGRAPHY;
PERIPHERAL VASCULAR NONINVASIVE MEASUREMENTS.
INTRODUCTION
The relations among forces, motion, and deformation are
studied in the field of mechanics. Biomechanics seeks to
understand the mechanics of living systems (1). The teeth
and jaw perform the critical function of initiating the
digestion by breaking the food into smaller sizes. This
increases the surface area of the food and improves the
effectiveness of the enzymes involved in digestion. Mastication is defined as the action of chewing foods. The masticatory system is composed of
1. The dention
2. The bones (the maxilla the mandible, and the
temporal bone),
3. The ligaments
4. The muscles
5. The temporomandibular joint (TMJ):
411
but are not limited to, prosthodontic and orthodontic treatments, reconstructive surgery, and reconstructive prosthetics. In this article, the biomechanical considerations in
prosthetic dentistry, including dental implant treatments,
intracoronal and extracoronal restorations, and fixed and
partial dentures, are reviewed.
412
Figure 2. (a) The mandibular dental arch and (b) the maxillary dental arch. (From Sobotta Atlas of
Human Anatomy Vol. 1, 13th ed.).
413
414
Table 1. Elastic Properties of the Enamel, Dentin Layers of a Tooth and the PDL
Enamel
Dentin
PDL
Poissons ratio v
80b,c
14 , 15b, 18a, 20b
0.002c, 0.003a 0.05b, 10d
0.3b
0.15 , 0.31b,c
0.45c, 0.49b,d
Tensile Strength
[MPa]
Compressive Strength
[MPa]
Shear Strength
[MPa]
10a
48a
288400a
232297a
8a
20a
415
THE TMJ
416
417
418
419
and s xy Gg xy
(1)
feg Cfsg
(2)
where the stress vector is {s} {sxx syy szz sxy syz szx}T, the
strain vector is {e} {ex ey ez gxy gyz gzx}T, the elasticity
matrix is [E], and the compliance matrix is [C] ( [E]1).
The elasticity matrix of an anisotropic material has
21 independent components. In case the material has three
orthogonal planes of symmetry, the material is said to be
orthotropic. The compliance matrix for an orthotropic
420
v31 =E3
v32 =E3
1=E3
1=G23
1=G31
1=G12
3
7
7
7
7
7 3
7
7
7
7
7
7
5
where Ei are the Youngs modulii, Gij are the shear modulii,
and vij are the Poissons ratios in the respective directions,
with the restriction that v12/E1 v21/E2, v13/E1 v31/E3,
and v32/E3 v23/E2. The number of independent elastic
constants is reduced to five for a transversely isotropic
material, such as the bone, where each plane through a
longitudinal axis is a plane of elastic symmetry. For fully
isotropic materials, the material properties are the same in
all directions, and two independent properties (E, v) are
sufficient to describe the stress-strain relationship.
Mechanical Properties of Bone
Bone is composed of collagen, water, hydroxyapatite
mineral, and small amounts of proteoglycans and noncollagenous proteins. Collagen is the structural protein that
gives the flexibility and tensile strength, also found in
ligaments and the articular disk. Hydroxyapatite,
Ca10(PO4)(OH)2, is a crystal with hexagonal symmetry
located within and between collagen fibers, found in the
form of needles, plates, and rods. The internal structure of
bone is porous. Two distinct porosity ranges give rise to the
cortical (compact) bone with low porosity (510%) and the
trabecular bone with 7595% porosity. The interstices are
filled with marrow, a tissue composed of blood vessels,
nerves and various types of cells (28).
Among these cells are the osteoclasts, which are responsible for formation of new bone, and osteoblasts, which are
responsible for resorption of bone. Remodeling of bone
involves repair of internal cracks, and so on, due to coupled
activity of osteoclasts and osteoblasts. In addition to selfhealing, the bone also has the ability to adapt to variations
in imposed stresses (Wolffs law). It has been hypothesized
that the strain in the bone tissue stimulates the biological
response resulting in adaptation (28). The physiologic
loading zone has been reported to be in the 1000
3000 microstrain range (28). Bone adaptation has significant biomechanical consequences, in design of endosseous
implants, and prosthetics. The loading conditions created
in the bone by these should be carefully considered to
prevent excessive or insufficient loading.
The cortical bone is a transversely isotropic material, as
two of its principal material directions have similar
mechanical constants. The stiffest direction of the mandibular cortical bone is along a tangent to the parabolic curve
of the mandible, i.e., direction -3 in Fig. 8 (29). The mechanical properties of the cortical bone depend on several fac-
E1 E2
E3
G12
G23 G31
v12 v21
v31 v32
v13 v23
Cortical Bonea
[GPa] (30)
Trabecular Boneb
[Gpa] (30)
13.0
19.0
5.3
5.9
0.22
0.42
0.29
0.27
0.82
0.12
0.12
0.19
0.34
0.11
a
b
Woo (11)
a
Location
Anterior
Central
Posterior
Medial
Lateral
Elastic Modulus
E[MPa]
a
2.34
1.48a
1.51a
1.11a
0.95a
0.79
Poissons
Ratio v
0.46
0.39
0.41
0.38
0.31
0.4
421
than the dynamic friction coefficient (1,18,38). This behavior is in contrast to the behavior of the COF between most
other materials (20).
Tension and compression tests of human articular disk
show nonlinear stress-strain behavior (14,39). Chin et al.
measured the viscoelastic properties of human TMJ disks
(40). Chen et al. (39) assumed that the solid matrix of the
articular disk can be modeled as a hyperelastic material of
the MooneyRivlin type (41), where the strain energy of an
incompressible rubber-like material is expressed as
U c1 I1 3 c2 I2 3
Poissons Ratio v
1.8
6.0
6.8
47.1a
44.1b and 92.4b
0.4
0.4
0.4
0.4
422
i1
i1
i1
where Nl, Nt, and Nj are the total number of force vectors
related to the ligaments, teeth, and joint reaction forces.
The location of each force vector is represented by a
location vector ~
r i . Each force vector causes a moment
with respect to the origin of the location vector repre~. The moment
sented by the vector cross-product ~
rF
balance with respect to the origin is expressed by the
moment equilibrium equation:
Nl
Nm
Nt
X
X
X
! m
! l
! t
! m
! l
! t
r i Fi
r i Fi
r i Fi
i1
i1
Nj
X
! j
! j
r i Fi 0
i1
i1
Nj
Nm
X
X
! m
! j
m
ci j F i j
ci j j F i j
i1
77
i1
~
jF
i
~m j
j mjF
Max
i
~m j
jF
Max
i
where
is the maximum possible for of the muscle
and m is a coefficient defined below. The maximum muscle
force of a muscle element is assumed to be proportional to
its physiological cross-section, and it is a known quantity.
The objective function was given as
m
~
f jF
i
j m
423
10
X!
MG
11
g Cu fu g
Mfu
I fug Cu fug
12
424
The jaw-opening and closing simulations were performed by Koolstra and van Eijens using equation 12 in
their dynamic model (54). In this work, they included the
jawopening muscles, in addition to the closing muscles. The
activation level A(t) was kept constant, and all muscles
were activated simultaneously. It was found that the level
of activation of the temporalis muscle parts was critical in
jaw-closing movements. The amount of jaw opening was
limited by the passive forces of the jaw-closing muscles.
However, the amount of jaw closing was not significantly
influenced by the passive forces of the jaw opening (54). The
TMJ remained loaded throughout the jaw movements.
They also concluded that the average moments generated
by the jaw-closing muscles, with respect to the center of
mass of the mandible, are responsible for stable operation
of the TMJ (52,54).
The lateral deviation of the jaw from the closed position
was also modeled by Koolstra and van Eijens (24). They
found that laterodeviations that conform to the naturally
observed ones could be generated by unilateral muscle
contractions. Their analysis concluded that movements
of the jaw predominantly depend on the orientation of
the contributing muscles with respect to the center of mass,
and not on the TMJ ligaments or passive elastic muscle
properties (24).
Deformations of the Mandible
Forces applied to the mandible cause internal stress
response within the mandible. Highest masticatory loads
are experienced when the maxillary and mandibular teeth
are in contact. During typical chewing, such high load
contacts last on the order of 0.1 s for chewing strokes and
longer for swallowing. At the end of the day, 1530 min of
high loads are experienced by the masticatory system.
persons with parafunctional habits, such as bruxism, may
experience longer durations of high levels of loading (4).
The stress and strain distribution in the mandible
change in response to the loss of teeth (30), mandibular
reconstruction (56,57) TMJ reconstruction, presence of
dental implants (58), or prosthesis (59); consequently,
the mandible changes its geometry and material property
distribution (30). Analysis of the internal stresses in the
mandible has, therefore, a potential to aid treatment. The
deformations and internal stresses of the masticatory
system could be evaluated by modeling the mandible as
a curved beam (60), using the photoelastic method (4) or by
strain measurements. The nonuniformity of the crosssectional area and that of the trabeculae of the mandibular
bone, and the presence of the teeth, prevent the beam
theory from being an accurate tool of analysis. On the
other hand, the photoelastic method provides a good visualization of the internal stress distribution (4). But the
trabecular architecture is generally not included in the
photelastic models. The strain measurements in vivo or in
vitro can only be performed on the surface of the bone.
The finite element method offers a suitable alternative
to model the geometric and material variations of the
mandible. Detailed analysis using FEA comes at a high
computational expense. However, combined with experimental strain measurements and the photoelastic method,
425
426
support, stability, comfort, function, and aesthetics. Removable partial dentures are subject to a combination of forces
arising from three different fulcrums on horizontal, sagittal, and vertical planes. As described for other treatment
modalities, planning is aimed at directing forces along the
long axes of the teeth as much as possible. Factors that
influence the amount of stress transmitted to abutment
teeth include length of the edentulous span, quality of the
ridge support, clasp design flexibility and material, and
occlusal harmony.
Tooth loss in an arch varies significantly in number and
location; therefore, removable partial dentures are often
designed based on available support (tooth supported, or
toothtissue supported). When the tooth loss pattern
allows a tooth-supported RPD, design issues are less complex. However, posterior free end scenarios present specific problems because the denture will be supported both
by teeth and tissues. Under function, healthy teeth may be
displaced as much as 0.2 mm, whereas tissue may be
displaced 1.0 mm or more. Thus, prevention of moments
on the terminal abutment teeth (teeth that are next to the
edentulous space) has been a major concern for tooth
tissue-supported prosthesis. To minimize moments,
various clasp assembly designs, resilient precision attachments, and stress breaking mechanisms have been proposed.
Recently dental implants have been used to assist RPDs
in retention and support.
Complete dentures are indicated in total edentulism.
For patients that cannot adapt to complete dentures, use of
dental implants is indicated. Retentive mechanisms for
implant-assisted dentures vary from individual attachments to bar systems, joining multiple implants. There
are many variations to individual attachments as well as to
A dental implant is a prosthetic device of alloplastic material implanted into the oral tissues beneath the mucosa and
periosteal tissues and into the jaw bone to support a fixed or
removable prosthesis. A dental implant system serves as
the anchor for the prosthetic reconstruction of missing
teeth by supporting a fixed or removable prosthesis. The
system mainly consists of an implant and an abutment. A
prosthetic attachment is typically fixed on the abutment by
one of the following methods: cementation, use of an occlusal screw, or a socket arrangement that allows retention of
a removable prosthesis.
The implant is the component implanted into the bone
tissue and serves the function of the root. Upon surgical
placement of the implant, a healing period of 26 months is
allowed during which osseointegration takes place. From
the patients point of view, a fixture is considered osseointegrated if it provides a stable and apparently immobile
support of a prosthesis under functional loads, without
pain, inflammation or loosening (66). During osseointegration, new bone forms in contact with the implant and a
direct structural and functional connection is established,
without initiating an immune response (rejection). Mineralized tissue is found to be in contact with the implant
surface over most of the surface within nanometers (66).
Relative movement (micromotion) between the implant
and the bone at the time of placement is more likely to
favor development of an fibroosseous interface (28). The
presence of the implant modifies the mechanical environment in its surrounding, by altering the normal physiology,
distribution of the fluids, and force transmission (28).
Nevertheless, dental implants have high long-term success
rates (67,68) due to careful bioengineering of the choice of
materials (69), surface topography and coatings, overall
size and shape of the implant body, and thread shape.
The abutment is the component that supports and/or
retains the prosthesis (70). The abutment is secured to
the implant with a mechanical attachment method, and
ideally, it should stay fixed with respect to the implant
throughout the life of the implant. Currently, three methods are used to attach an abutment onto an implant. In the
most common mechanical attachment method, an abutment retaining-screw is used to fix the abutment with
respect to the implant (70). The mechanics of this type of
screwattachment are analyzed by classic methods (71) and
the FEA (72). Another approach is to use a screw with a
relatively large tapered end (73). Finally, in some implant
systems, a tapered interference fit between the abutment
and the implant is also used to provide the connection
(74,75).
From a bioengineering perspective, an important issue
is to design the implant with a geometry that will minimize
the peak bone stress caused by standard loading (76). The
complex geometry of the implants prevents the use of
closed-form solutions in stress analysis, where simple formulas relate the effect of external loads to internal stresses
427
428
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35. Van Oosterwyck H, Duyck J, Vander Sloten J, Van Der Perre
G, De Cooman M, Lievens S, Puers R, Naert I. The influence
of bone mechanical properties and implant fixation upon bone
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36. Mow V, Kuei SC, Lai WM, Armstrong CG. Biphasic creep and
stress relaxation of articular cartilage in compression: Theory and experiments. J Biomech Eng 1980;102:7384.
37. Hu K, Radhakrishnan P, Patel RV, Mao JJ. Nanomechanical
and topographic properties of the articular fibrocartillage of
the rabbit mandibular condyle. J Struct Biol 2001;136:281
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38. Linn FC. Lubrication of animal joints. I, The arthrotripsometer. J Bone Joint Surg 1967;49A:1079.
39. Chen J, Akyuz U, Xu L, Pidaparti RMV. Stress analysis of the
human temporomandibular joint. Med Eng Phys 1998;20:
565572.
40. Chin LPY, Aker FD, Zarrinnia K. The viscoelastic properties
of the human temporomandibular joint disk. J Oral Maxillofacial Surg 1996;54:315318.
41. Belytschko T, Liu WK, Moran B. Nonlinear Finite Elements
for Continua and Structures. Chichester: Wiley; 2004.
42. Chen J, Xu L. A finite element analysis of the human
temporomandibular joint. J Biomech Eng 1994;116:401
407.
43. Tanaka E, Kazuo T, Sakuda M. A three-dimensional finite
element model of the mandible including the TMJ and its
application to stress analysis in the TMJ during clenching.
Med Eng Phys 1994;16:316322.
44. Hu K, Qiguo R, Fang J, Mao JJ. Effects of condoylar fibrocartillage on the biomechanical loading of the human temporomandibular joint in a three-dimensional, non-linear
finite element model. Med Eng Phys 2003;25:107113.
45. Viidik A. Properties of tendons and ligaments. In: Skalak R,
Chien S, editors. Handbook of Bioengineering. New York:
McGraw-Hill; 1988. 119.
46. Smith DM, McLachlan KR, McCall WD. A numerical model of
temporomandibular joint loading. J Dent Res 1986;65:1046
1052.
47. Osborn JW, Baragar FA. Predicted pattern of human muscle
activity during clenching derived from a computer assisted
model: Symmetric vertical bite forces. J Biomech
1985;18:599612.
48. Strang G. Introduction to Linear Algebra. Cambridge, MA:
Wellesley-Cambridge Press; 1998.
49. Hatcher DC, Faulkner MG, Hay H. Development of mechanical and mathematic models to study temporomandibular
joint loading. J Prosthetic Dentistry 1986;55:377384.
50. Koolstra JH, van Eijden TMGJ, Weijs WA, Naeije M. A threedimensional mathematical model of the human masticatory
system predicting maximum possible bite forces. J Biomech
1988;21:563576.
51. Koolstra JH, van Eijden TMGJ. Application and validation of
a three-dimensional mathematical model of the human masticatory system in vivo. J Biomech 1992;25:175187.
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75. Bozkaya D, Mu ftu S. Efficiency considerations for the purely
tapered interference fit (TIF) abutments used in dental
implants. J Biomech Eng 2004;126:393401.
76. Hansson S. The implant neck: smooth or provided with
retention elements: A biomechanical approach. Clin Oral
Implants Res 1999;10:394405.
77. Holmgren EP, Seckinger RJ, Kilgren LM, Mante F. Evaluating parameters of osseointegrated dental implants using
finite element analysisa two-dimensional comparative
study examining the effects of implant diameter, implant
shape, and load direction. J Oral Implantol 1998;24:8088.
78. Rieger MR. Finite element stress analysis of root-form
implants. J Oral Implantol 1988.; 14:472484.
79. Rieger MR, Adams WK, Kinzel GL. A finite element survey of
eleven endosseous implants. J Prosthet Dent 1990;63:457
465.
80. Siegele D, Soltesz U. Numerical investigations of the influence of implant shape on stress distribution in the jaw bone.
Int J Oral Maxillofacial Implants 1989;4:333340.
81. Pierrisnard L, Hure G, Barquins M, Chappard D. Two dental
implants designed for immediate loading: A finite element
analysis. Int J Oral Maxillofacial Implants 2002;17:353362.
82. Van Oosterwyck H, Duyck J, Vander Sloten J, Van Der Perre
G, Naert I. Peri-implant bone tissue strains in cases of
dehiscence: A finite element study. Clin Oral Implants Res
2002; 13:327333.
83. Papavasiliou G, Tripodakis AP, Kamposiora P, Strub JR,
Bayne S. Finite element analysis of ceramic abutmentrestoration combinations for osseointegrated implants. Int
J Prosthodont 1996;9:254260.
84. Stegaroiu R. Kusakari H, Nishiyama S, Miyakawa O. Influence of prosthesis material on stress distribution in bone and
implant: A 3-dimensional finite element analysis. Int J Oral
Maxillofacial Implants 1998;13:781790.
85. Stegaroiu R, Sato T, Kusakari H, Miyakawa O. Influence of
restoration type on stress distribution in bone around
implants: A three-dimensional finite element analysis. Int
J Oral Maxillofacial Implants 1998;13:8290.
86. Misch CE, Waren Bidez M. A scientific rationale for dental
implant design. In: Misch CE, editor. Contemporary Implant
Dentistry. St. Louis: Mosby; 1999. 329343.
87. Misch CE, Waren Bidez M, Sharawy M. A bioengineered
implant for a predetermined bone cellular response to loading
forces. A literature review and case report. J Periodontol
2001; 72:12761286.
88. Misch CE, Dietsh-Misch F, Hoar J, Beck G, Hazen R. A bone
quality-based implant system: first year of prosthetic loading.
J Oral Implantol 1999;25:185197.
89. Misch CE. Implant design considerations for the posterior
regions of the mouth. Implant Dent 1999;8:376386.
90. Chun HJ, Cheong SY, Han JH, Heo SJ, Chung JP. Evaluation of design parameters of osseointegrated dental implants
using finite element analysis. J Oral Rehabil 2002;29:565
574.
See also BONE AND TEETH, PROPERTIES OF; BIOMATERIALS FOR DENTISTRY;
JOINTS, BIOMECHANICS OF.
See NUTRITION,
429
TRACER KINETICS
EDWARD V. R. DI BELLA
University of Utah
Salt Lake City, Utah
INTRODUCTION
Tracer kinetics refers to the changing distribution of a
tracer that provides information regarding a biological
system. The tracer may be introduced by injection into
the bloodstream, or inhaled, or in some cases be native. By
definition, the tracer is present in relatively small (trace)
amounts so that it has little or no effect on the system being
studied.
A large variety of tracers, along with methods for their
measurement, are employed daily in numerous medical
applications. Imaging function with tracers can provide
complementary or more relevant information than anatomical imaging. For example, positron emission tomography
(PET) and single photon emission computed tomography
(SPECT) imaging can track radiolabeled tracers to detect
and stage cancer, to assess neural function, to follow
response to therapy, and to detect heart disease. Magnetic
resonance imaging (MRI) with paramagnetic contrast acting as a tracer is a rapidly growing area, as is ultrasound
with tracer-like microbubbles. Over 1 million patients are
imaged annually in the United States for oncology applications. Over 7 million/year have a cardiac SPECT scan,
mostly for the diagnosis of coronary artery disease.
How do these tracers work? Two brief examples will help
to illustrate the process. The first example is of tracer
applications that are suitable for analysis at equilibrium.
That is, the kinetics portion of Tracer Kinetics is not used
directly, but rather serves only to bring the tracer to some
equilibrium state. The second example is of a radiolabeled
glucose analogue, which is most often analyzed as if it were
at equilibrium, but offers more information when its changing distribution over time is considered as well. This will
provide a feel for the field of tracer kinetics and for the
controversy sometimes surrounding the use of tracer
kinetics with quantitative modeling methods, compared
to visualization of static images of tracer distribution.
Static Tracers
By far, the bulk of clinical radionuclide studies use static
images acquired while the tracer distribution is changing
slowly or is fixed. Microsphere-type tracers are the simplest case of this type of tracer. These tracers provide a
static distribution after their first pass and may be, for
example, 99mTc-labeled albumin, or in studies with animals
that will be sacrificed, 1015 mm diameter carbonized
microspheres tagged with radioactive or fluorescent labels.
Such tracers lodge in capillaries in proportion to flow. The
microspheres must be infused into the left atrium or left
ventricle or will all be trapped in the lungs. Absolute flow
values in milliliters per minute per gram (mL/min/g) can be
computed using these tracers. However, the amount of
tracer in the region of interest must be known. For animal
studies with microspheres, this is done by excising the
430
TRACER KINETICS
k3
k1
Blood
C3(t)
C2(t)
k4
k2
TRACER KINETICS
Tissue Intracellular
Tissue - Interstitial
Capillary membrane
Vascular - plasma
Vascular - red
blood cells (Hct)
Figure 2. A compartment model type view of a section of capillary
(lower two segments) and a section of tissue. The arrows represent
the exchange that would occur with an extracellular tracer such as
gadolinium. Water would distribute throughout all four regions
shown.
COMPARTMENT MODELING
By kinetic modeling we refer to using any of a number of
quantitative approaches to extracting information from a
time series of data. All of these approaches invoke some
sort of mathematical model in order to parameterize the
data. The idea is that the parameters can provide more
information than processing without models or simple
visual examination of the data can provide.
Depending on the type of tracer or contrast agent used,
and on the fidelity and resolution of the signal, appropriate
models can be selected. That is, the models should not
include detail that cannot be discriminated by the measured data, even if it is known to exist physiologically. In
practice, almost all models will be required to be simplified
versions. The models also need to have useful parameters
for the task at hand. Compartment models are widely used
for a number of applications due to their relative simplicity
and physiological relevance.
A compartment refers to a well-mixed volume in a
system of interest that can be considered to have a homogeneous concentration of the tracer. A widely used compartment model of interest is the two compartment model
(Fig. 2). This case is often an extremely useful approximation to the system of interest. For example, one compartment is considered to be the vasculature, and one
compartment is the tissue of interest. The washin and
washout rate constants k1 and k2 (or Ktrans and kep) govern
the concentration in the tissue compartment. The driving
compartment, the arterial input function, is usually considered to be measured or otherwise known. For this
reason, some authors call this a one compartment model.
Note that a compartment model is often used even in the
analysis of multiple heterogeneous regions. Typically, it is
assumed that all are driven by the same input function.
That is, the blood compartment is the same for all of the
regions, but the tissue kinetic parameters of uptake and
washout of each region may vary. The model remains the
same, but the parameters are different for each region.
Kety Model
The roots of compartment modeling approaches are found
in Ketys seminal work in the 1940s (3,4). Kety and
431
Schmidt were the first to successfully determine the cerebral blood flow (CBF) and oxygen consumption in a relatively noninvasive way. They had normal volunteers
breathe air with a 510% concentration of nitrous oxide.
The nitrous oxide that was used as a tracer is an inert gas
that is soluble in the brain tissue. They then applied the
Fick principle to determine CBF. The Fick principle is
simply mass balance for convective systems. Use of the
Fick principle gives
Z t
Qb t CBF
Ca t Cv tdt
(1)
0
Qb
0 Ca t Cv tdt
Rt
lCv t
0 Ca t Cv tdt
(2)
Here the venous concentration times l, which is the solubility constant or partition coefficient for nitrous oxide, is
used as a measure of the amount of tracer in the brain at
equilibrium. The partition coefficient refers to the concentration of the tracer in the tissue divided by the concentration in the blood at equilibrium (at equilibrium arterial and
venous blood ideally have the same concentration).
Another way to consider the partition coefficient is as a
virtual volume, relative to the volume the tracer distributes in a unit of blood. Thus l is also called the distribution volume. For water, l 1. For nitrous oxide l 0.48
mL/mL. The parameter l is also sometimes given in units
of g/g or mL/g when the density of blood is 1.06 g/mL or
the specific gravity of gray or white matter 1.05 are used.
For an extracellular tracer such as gadolinium-diethylenetriamine penta-acetic acid (DTPA), l 0.3. Figure 2
shows a graphic interpretation of the distribution volume
for gadolinium.
In practice, venous measurements of nitrous oxide concentration are taken from an internal jugular vein, and
arterial concentrations from a peripheral arterial line. This
gives an accurate measure of whole brain CBF, 50 mL/
(min100 g) in normal humans.
PET H215O Compartment Model
Interestingly, at first glance Ketys use of the Fick principle
does not appear to link to most of todays compartment
models. The approach today is often to write a system of
differential equations to describe the behavior of the tracer,
and then solve the equations to get a form such as:
Ct t Ca t k1 ek2 t
(3)
where denotes convolution, and the arterial input function Ca(t) convolved with one or more exponential terms is
TRACER KINETICS
dCt
k1 Ca k2 Ct
dt
(4)
Blood Input
Measured Uptake
Fit (Model)
1.5
1
0.5
0
0
50 100 150
Time (seconds)
200
(a)
Gd concentration (mmol)
fit to the measured image data Ct(t). Though the Kety form
has no derivatives or convolutions, Ketys Eq. 2 can be
rearranged in a similar form. This rearrangement is illustrated by describing the use of a two compartment model
for PET H2 15 O. Water rapidly diffuses across capillary and
cellular membranes, so one can postulate based on Fig. 2
that the rate of change of concentration in the tissue
compartment is equal to the input to the compartment
(the rate constant k1 times the arterial concentration)
minus the output from the compartment (Ct times the rate
constant k2).
Gd concentration (mmol)
432
(b)
2
Blood Input
Measured Uptake
Fit (Model)
1.5
1
0.5
0
0
(c)
Figure 3. (a) Time curves from measured uptake in region corresponding to arrow in the middle image, distribution volume
ve 0.58 mL/g. The blood input is from a region of interest drawn
on the left ventricle cavity. The fit is from a two compartment
model for gadolinium-DTPA. (b) Delayed image of a short axis
slice of the heart(right ventricle on left, left ventricle the large
doughnut structure with its endocardial wall traced in green) from
MRI acquired 15 min after contrast injection, showing subendocardial inferior infarct (arrow). (c) Curve from a remote normal
region, ve 0.37. The magnitude and spatial distribution of ve may
help characterize the infarct better than delayed enhancement
alone.
volume to distribute in within regions where cell membranes have been destroyed, since gadolinium is an extracellular tracer.
The volume/g of tissue that is occupied by cells in the
heart muscle is estimated as 70%. The interstitial space,
or distribution volume for Gd-DTPA, has been reported as
ve 0.3 mL/g in healthy tissue, where ve stands for volume
of extracellular extravascular space and is used in place of
the symbol l. This distribution volume increases if cell
membranes are disrupted as in acute myocardial infarction
(heart attack). Scar tissue, composed of a collagen matrix,
will still accumulate gadolinium if it is still perfused. This
is likely because the collagen matrix has more interstitial
space, but is still not completely understood (6).
Another issue for most tracers is that tissue regions of
interest contain on the order of 10% of their volume as
vasculature. Thus the time curve Ct(t) is biased by a
contribution from something similar to Ca(t). [Due to hematocrit changes in smaller vessels and delay and dispersion,
it may not be exactly Ca(t).] One method of accounting for
this is to include another parameter in the fit to estimate
the blood volume in the region of interest:
Ct t Ca tk1 ek2 t vb Ca t
(5)
TRACER KINETICS
remain freely available in the interstitial space, or undergoes a chemical trapping such as phosphorylation, requires
a more complex model. The two compartment model may
not be sufficient since the tissue now has two different pools
of nonuniform concentrations. Note that these pools generally are not measured separately (Fig. 1). The two compartment model can still be used as an approximation, but
a three-compartment model (Fig. 1) is likely more appropriate. A more complex model with four compartments has
also been proposed for the case of FDG uptake in skeletal
muscle (9).
Gd concentration (mmol)
Epicardial
Blood Input
Measured Uptake
Fit (Model)
2
1.5
K trans = 0.53
ve = 0.29
vb = 0.01
1
0.5
0
0.5
20 40 60 80 100 120
Time (seconds)
(a)
433
(b)
Gd concentration (mmol)
Endocardial
2
Order of Model
Blood Input
Measured Uptake
Fit (Model)
1.5
K trans = 0.43
ve = 0.29
vb = 0.19
1
0.5
0
0
20 40 60 80 100 120
Time (seconds)
(c)
Figure 4. Short axis dynamic cardiac MRI time series study. (a)
MRI image precontrast. Epicardial (light blue) and endocardial
(orange) regions that give the tissue curves in (b) and (c) are
marked. Parts (b) and (c) use the same blood input function and
should have similar flows as implied by the Ktrans (Ktrans k1)
values given. The point here is that due to partial volume effects,
typical upslope or percent enhancement semiquantitative measures would incorrectly give very different flow indices for the two
regions. The model used Eq. 5 to obtain blood volume vb values to
compensate for partial volume effects.
(6)
434
TRACER KINETICS
Z1
Ct tdt=Ct 0
The mean transit time is on the order of 5 s for nondiffusible intravascular tracers in the brain, and on the order of
minutes for diffusible tracers (14). Or one can define the
mean transit time as the inverse of the washin rate constant, 1/k1(14).
Other easily computable parameters such as maximum
upslope, percent signal enhancement, area under the
curve, or the time until peak signal have been suggested
and used as model-free approaches.
ESTIMATING KINETIC PARAMETERS
Weighted Least Squares
The estimation of kinetic parameters from noisy data is a
well-studied problem. The errors in the parameters can be
estimated based on the variance in the data. The model can
be written as:
Ct t htCa t e
(7)
(8)
(9)
meters (i.e., dy/dp A) then the best linear unbiased estimate, the estimate with minimum variance (16), is given by
p AT F1 A1 AT F1 y
(10)
(11)
(12)
M
X
m1
pm mpm m1=M
M
X
1
Am Fm Am 1 (13)
m1
TRACER KINETICS
of the parameter estimates. The parameter M is the number of regions (assumed homogeneous) and m is used to
index the M regions. This approach is equivalent to a
specific case of ridge regression (22). These Bayesian methods represent a new class of analysis techniques for tracer
kinetics.
IMPROVING AND AUTOMATING ANALYSIS OF THE
KINETIC TRACER CURVES
While some applications have sufficient signal-to-noise ratio
(SNR) to perform pixelwise analysis of the kinetic tracer
curves, other applications can benefit greatly from spatial
averages of the data. Methods such as factor analysis and
clustering can be useful for automatically identifying blood
and tissue curves from the image series data (23). This
approach may give better kinetic parameter estimates
and be more automated than manual delineation of regions.
Factor Analysis
Factor analysis, also termed FADS, which stands for Factor Analysis of Dynamic Structures, has been somewhat
widely used in nuclear medicine applications (2427). The
FADS is essentially principal components analysis followed by a rotation to satisfy nonnegativity conditions.
While this does not provide a unique solution, several
different FADS methods have been validated as clinically
useful for certain tasks. As well, a number of modifications
to the basic method to incorporate additional information
have been proposed, for example, (27).
Clustering
Clustering is becoming a popular method for a data-driven
approach to choosing the regions. K-means clustering, also
termed c-means clustering, groups alike timeactivity
curves (or time-concentration curves) by computing a distance between each pair of curves and grouping curves into
the cluster that they are closest to. The cluster centers are
updated (continuously or at discrete intervals). Most often
a Euclidean distance is used to determine to which cluster a
voxel belongs.
It is still an open issue to make factor analysis, clustering, and automated approaches robust and clinically practical. Quantitative imaging finds particular importance for
longitudinal studies. These studies also need robust registration and processing methods to perform well.
Since a number of the analysis methods are nonlinear, it
is typically left to empirical task-specific studies to determine if specific image processing methods can significantly
impact the accuracy or robustness of the results.
ISSUES WITH THE ARTERIAL INPUT FUNCTION, AIF
Importance of an Accurate AIF
In order to obtain accurate absolute measures of kinetic
parameters, it is important to use an accurate arterial
input function. This is critical for any of the models or
model-free approaches that use the AIF. Accurate input
435
(14)
(15)
Then convolving both sides of Eq. 16 with h2(t) and substituting from Eq. 12 gives the cross-relation expression
(29):
h2 ty1 t h2 tb th1 t
|{z}
y1 th2 t y2 th1 t
436
TRACER KINETICS
INTRODUCTION
The field of pain management is a rapidly expanding one,
and new treatment modalities are being discovered or
rediscovered. Electroanalgesia has a long and sometimes
dubious history, dating back to the ancient Egyptians.
However, the publishing of the gate control theory of
pain transmission in 1965 by Melzack and Wall transformed our understanding of pain, its transmission, and
how it is modulated. With this discovery, electroanalgesia
underwent a revolution, and transcutaneous electrical
nerve stimulation (TENS) was developed and is continually being refined. Today, our understanding of the
mechanism by which TENS produces analgesia continues
to expand does its potential applications.
This article provides a review of pain, its definition,
types, and physiology. It provides background information
and theories surrounding the mechanism of analgesic
action of TENS and the development of electroanalgesia.
It discusses the usage, design, applications, and warnings
surrounding TENS.
WHAT IS PAIN?
Pain is an unpleasant sensory and emotional experience
associated with actual or potential damage, or described in
terms of such damage. Pain serves as an essential defense
mechanism to protect ones body from potential damage.
Indeed, the disastrous consequences of diminished or
437
438
I
C fiber
II
III
A fiber
IV
V
VI
A,
Figure 2. Nociceptive afferent fibers terminate on projection neurons in the dorsal horn of the spinal cord. Projection neurons in
lamina I receive direct input from myelinated (Ad) nociceptive
afferent fibers and indirect input from unmyelinated (C) nociceptive afferent fibers via stalk cell interneurons in lamina II. Lamina
V neurons are predominately of the wide dynamic-range type. They
receive low threshold input from the large-diameter myelinated
fibers (Ab) of mechanoreceptors, as well as both direct and indirect
input from nociceptive afferent fibers (Ad and C). In this figure the
lamina V neuron sends a dendrite up through lamina IV, where it is
contacted by the terminal of an Ab primary afferent. A dendrite in
lamina III arising from a cell in lamina V is contacted by the axon
terminal of a lamina II interneuron. (Adapted from Ref. 4.)
Voltage
(a)
A
C
Time
(b)
A fiber
First
pain
Second
pain
C fiber
Pain
intensity
A fiber
Time
439
Figure 3. Three of the major ascending pathways that transmit nociceptive information from the
spinal cord to higher centers. The spinothalamic tract is the most prominent ascending nociceptive
pathway in the spinal cord. (Adapted from Ref. 7.)
440
Source
Potassium
Serotonin
Bradykinin
Histamine
Prostaglandins
Leukotrienes
Substance P
Damaged cells
Platelets
Plasma kininogen
Mast cells
Arachidonic aciddamaged cells
Arachidonic aciddamaged cells
Primary afferents
Tryptophan hydroxylase
Kallikrein
Cyclooxygenase
5-Lipoxygenase
THEORIES OF PAIN
Gate Control Theory
The gate control theory, published in 1965 by Ron Melzack
and Pat Wall (10), was the theory from which modern
electrotherapy has evolved and that has helped revolutio-
Input
SG
Action
system
441
442
(a)
Nociceptor
Norepinephrine
Serotonin
ENK
Projection
neuron
Nociceptor
Control
Opiate
Glutamate
Neuropeptides
Glutamate
Neuropeptides
Enkephalin
Ca2+
Morphine
Enkephalin
Ca2+
No input
Sensory input
Control
Projection
neuron
No input + opiates
Enkephalin
Sensory input + opiates
Control
Enkephalin
Figure 5. Local-circuit interneurons in the superficial dorsal horn of the spinal cord integrate
descending and afferent pathways. (a) Possible interactions between nociceptor afferent fibers, local
interneurons and descending fibers in the dorsal horn of the spinal cord. Nocicaptive fibers terminate on second-order spinothalamic projection neurons. Local enkaphalin-containing interneurons (ENK) exert both presynaptic and postsynaptic inhibitory actions at these synapses.
Serotonergic and noradrenergic neurons in the brain stem activate the local opioid interneurons
and also suppress the activity of spinothaiamic projection neurons. (b) 1. Activation of nociceptors
leads to the release of glutamate and neuropeptides from sensory terminals in the superficial dorsal
horn, thus depolarizing and activating projection neurons. 2. Opiates decrease the duration of the
nociceptors action potential. probably by decreased Ca2 influx and thus decrease the release of
transmitter from primary afferent terminals. In addition, opiates hyperpolarize the mambrane of
the dorsal horn neurons by activating a K conductance. Stimulation of the nociceptor normally
produces a fast excitatory postsynaptic potential in the dorsal horn neuron opiates decrease the
amplitude of the postsynaptic potential.
443
Figure 6. This represents one of the earliest families of stimulators, with the original model seen on the left. The first personal
patient treatment model is depicted on the right, and a prototype
for a miniaturized design is shown in the center. The original
sponge electrodes are depicted in the foreground.
444
121
136.2
7.1 10.1
3.4
8.4 2.5
6.3
9.5 6.4
2.5
Rehabilicare/
ProMax
Rehabilicare/
Maxima3
Rehabilicare/
SMP-Plus
132
132
226
266
9.9 6.98
2.54
9.5 6.3
3.2
8.2 7.0
4.5
BioMedical Life
Systems/
BioStim LX
BioMedical Life
Systems/
BioStim M7
BioMedical Life
Systems/
BioMed 2000
BioMedical Life
Systems/
BioStim A6
9.9 6.98
2.54
Empi/Epix XL
Empi/Epix VT
122.2
Size, cm
Manufacturer/unit
4 AA Batteries
4 AA Batteries
9 V Battery
9 V Battery
9 V Battery
9 V Battery
Digital
Digital
Analog
Analog
Analog
Digital
Digital
Analog
Stimulus
Modes
Pulse
Digital/
Width,
Analog
ms
Weight,
g
Power source
Cycled
Cycled
Cycled
8 pulses/burst;
Burst at 2 Hz
Varies
Varies
Asymmetric
rectangular
biphasic
Asymmetric
rectangular
biphasic
Symmetrical
biphasic square
zero net charge,
Asymmetric
rectangular
biphasic
Asymmetric
rectangular
biphasic
Balanced
asymmetrical
biphasic
Asymmetric
rectangular
biphasic with
zero net dc
Biphasic,
asymmetrical
with zero net dc
Biphasic,
asymmetrical
with zero net dc
Channels Waveform
8 pulses/burst;
Burst at 2 Hz
8 pulses/burst;
Burst at 2 Hz
8 pulses/burst;
Burst
098
198
0100
080
060
060
060
0100
0100
Output
Current,
mA
1200
1150
2200
2150
2150
2150
2125
2160
2160
Output
Rate, Hz
445
Shining World
12.5 6.6
Health Care Co./
2.8
SW 325
Body Clock
10.5 6.5
Healthcare/
2.75
Profile
Med-Dyne/TA3
9.1 6.4
2.3
9 V Battery
130
9 V Battery
2 AA Batteries
130
9.1 6.4
2.3
ProMed
Specialties/
ProM 300
9 V Battery
100
130
9.1 6.4
2.3
ProMed
Specialties/
ProM 200
9 V Battery
9 V Battery
130
9.1 6.4
2.4
ProMed
Specialties/
ProM 100
9 V Battery
138
134
9.85 6.05
2.45
Pain
Management
Technologies/
Medscope Pro
Pain Management
Technologies/
Bioscope
Analog
Digital
Digital
Analog
Analog
Analog
Analog
Digital
Analog
UM-1 6
Battery or
9 V dc
adapter
9 V Battery
1060.5
140
Analog
9 V Battery
130
Digital
9.1 6.4
2.3
40.6 18.5
6.8
2 AA Batteries
132
Digital/
Analog
9.9 6.98
2.54
Size, cm
Weight,
g
Power source
10.1 5.9
2.37
BioMedical Life
Systems/
BioStim
Plus
Vital/TENS
Deluxe
Kingly Star/
KS-168
Manufacturer/unit
Table 2. (Continued)
Stimulus Modes
Constant
25250 Constant,
Burst, Width modulation,
Rate modulation
40260 Constant, Burst,
Modulation
200
9 pulses/burst;
burst at 2 Hz
Variable
n/a
Channels
7 pulses/burst;
Burst at 2 Hz
7 pulses/burst;
Burst at 2 Hz
7 pulses/burst;
Burst at 2 Hz
Cycled/
2 presets
Burst
Pulse
Width,
ms
Symmetric
biphasic
rectangular
Asymmetric
biphasic square
with zero net
current dc
Asymmetric
biphasic square
with zero net
current dc
Asymmetric
biphasic square
with zero net
current dc
Asymmetric
biphasic square
with zero net
current dc
Biphasic
Spiked Wave
Biphasic
square wave
with zero
net dc
Asymmetric
biphasic
square
Asymmetric
biphasic,
square wave
Waveform
1200
2160
080
250
2120
2150
2150
2150
2200
2120
1150
Output
Rate, Hz
0100
050
080
080
080
015
080
0100
variable
098
Output
Current,
mA
446
Number
of Uses
Typical Retail
Cost Electrode
(pair)
Disposable
1 use
Under $3.00
Semireusable
310 uses
$5.0010.00
Reusable
>100 uses
$4.00a
Adhesion and
Conduction
Composition
Materials
Pressure-sensitive
tape surrounding
conductive area
(wet get in sponge)
Conductive
adhesive over
entire surface
Nonwoven
Foam
Requires addition of
conductive gel and
tape adhesion
Carbon
silicone
Foam Plastic
film Carbon
silicone
Advantages
Disadvantage
Easiest to use
Very good
adhesion
Comfort
Ease of use Low
skin irritation
Comfort
Cost/use Skin
irritation Poor
electrical
performance
Weak adhesion
Care and storage
Medium cost per
use Good electrical
performance
Most preparation to
use Skin irritation
Messy Requires gel
and tape Skill
required for optimal
performance Poor
adhesion Not as
flexible in use
Sample Electrodes
Electrode Placement
Electrode placement is crucial in maximizing positive outcome with TENS units. Most units employ two or more
channels of current, which splits to two electrodes, and it is
often advisable for multiple channels to be used to cover
maximal areas, as many pain syndromes often do not
exhibit pain localized to a specific point source. Numerous
books on TENS or manufacturer information as well as
various anatomical charts provide users with possible
electrode placements. While it is impossible to describe
447
proper electrode placement for every pain syndrome, certain electrode arrangements are frequently used.
For the purposes of this discussion, the channels will be
referred to as I and II and the negative electrode as a and
the positive as b. Parallel placement with one channel is
utilized for relatively localized areas of pain, such as point
pain or pain from a surgical incision. Electrode Ia is placed
on one side of the incision, while Ib is on the other, producing a current that flows between the two with the area of
pain in between the electrodes. Bilateral placement is
similar, but generally defined as meaning Ia and Ib electrodes are placed on either side of the spine, symmetrically
and close together, useful for localized, nonradiating neck
or back pain. For radiating neck or back pain, a longitudinal arrangement is often utilized in which electrodes
of one channel are on the same side of the spine and placed
along the pain pathway. If the pain is bilateral, electrodes
of another channel on the can be placed on the opposite side
of the spine along the pain pathway (Fig. 9).
A crossed, or interferential, placement is useful for
pain localized to large joints, such as shoulder, elbow,
or knee. In this pattern, Ia and IIa are placed side by side
with IIb below Ia and Ib below IIa, creating a square
pattern with electrodes of the same channels diagonally
opposite each other with the area of pain in the center of
the square. Bracketed placement is generally reserved for
treating the dermatomal neuralgia that frequently is
associated with shingles, varicella zoster, out breaks. In
this arrangement, electrodes Ia and Ib are placed along
448
Figure 10. Dermatomal maps of the peripheral distribution of spinal nerves (a and b) and trigeminal nerve (c) d. Details of termatomal maps on anterior and posterior surfaces of the hand and
foot.
user experiences. If the user inadvertently places electrodes in a nonoverlapping pattern (i.e., Ia and Ib both proximal to IIa and IIb), the current will not cover the entire
pain pathway; instead it will only travel between electro-
449
450
asymmetric. If the current amplitude is equally positive and negative, the current is termed electrically
balanced, also referred to as zero net charge (znc) or no
net dc current. While both balanced and unbalanced electrical currents are employed, unbalanced current transmission can result in pH changes in the skin with longterm usage, do to ion exchange, which can result in skin
irritation. Additionally, the current employed in TENS is a
pulsatile current with interspaced periods of electrical
activity and electrical silence. The periods of electrical
silence may be either uniform or varying. The frequency
of electrical pulses may be given in units of hertz (Hz),
cycles per second (cps), or pulses per second (pps) (25). It is
important to note that while frequency may be a constant
100 cps, the period between the pulses may be variable.
All of these variables in the current waveform may be
adjusted to achieve a net effect that is both pleasant to the
patient while sufficient to achieve muscular contraction. For
example, the amplitude of the current may be varied over a
constant time interval, the duration of the pulse may be
varied, the time between pulses may be varied, or a combination of some or all of the previous may be used. As pain
severity and character can frequently change, models that
allow modulation of electrical current via one or more
characteristic offer distinct advantages in patients individualizing their therapy as well as help prevent physiologic
adaptation to the electrical stimulation. While numerous
studies have delved into optimizing the electrical waveform
(2628), their conclusions have been varied, and it is likely,
there is no optimal waveform. As such, TENS therapy is an
individualized one, and patients should have frequent follow
ups with their physician to ensure the patient is receiving
optimal care for their specific complaint (Table 4).
Facet syndrome
Intercostals neuralgia
Radiculitis
IVD Syndrome
Sprains/strains
Lumbago
Thoracodynia
Lumbosacral pain
Whole back pain
Lower Extremity Pain
Ankle pain
Passive stretch pain
Foot pain
Sciatica
Fractures
sprains/strains
Ischialgia
tendonitis
Knee pain
Thrombophlebitis
Upper Extremity Pain
Epicondylitis
Frozen shoulder
Sprains/strains
Hand pain
Subdeltoid bursitis
Peripheral nerve
Wrist pain
Injury
TREATMENT PLANS
Treatment with TENS is an extremely variable and personalized process, and this cannot be underscored enough.
It is vital for close healthcare supervision for a user to
obtain the maximum therapeutic benefit from tens. TENS
may only be used in an acute phase for a short period of
time (e.g., incisional pain postsurgery) or for months or
years (e.g., those suffering from chronic back pain). For
chronic pain sufferers classical TENS may be used for
several hours continuously daily. Modulated or low frequency/high intensity may be used for 30 min three
times a day for an indefinite period of time. When using
TENS it is important to use as strong or nearly asstrong a
current as the user can tolerate to achieve best results.
Fibromyalgia is a poorly understood chronic pain condition that presents unique management challenges not
only because it is poorly understood, but also because it is
often refractory to traditional treatment modalities. A
recent double-blinded study by Cork et al. (29) explored
cranial electrotherapy stimulation (CES) as a possible
treatment for fibromyalgia. In this study, using electrodes
clipped to the participants ear lobes, the Alpha-Stim CES
device, delivered either modified square-wave stimulation
at 100 mA and a 50% duty cycle at 0.5 Hz for 1 h daily for
3 weeks or sham therapy (see Fig. 15). While there were no
451
BIBLIOGRAPHY
452
24.
25.
26.
27.
28.
29. Cork R, et al. The Effect of Cranial Electrotherapy Stimulation (CES) on Pain Associated with Fibromyalgia. Int J
Anesthesiol 2004;8(2). Available at http://www.ispub.com/
ostia/index.php? xmlFilePath=journals/ija/vol8n2/ces.xml.
See also BLADDER
U
ULTRASONIC HYPERTHERMIA. See
HYPERTHERMIA,
Magnetostriction (1847) and the piezoelectric effect followed (1880 by Curie), and are still very much relevant
mechanisms for medical and industrial ultrasound. In
1918, it was found that the use of oscillating crystals could
be used to stabilize frequencies. The upper frequency for
sound in a given solid material is determined by the
separation of neighboring atoms in the host medium. This
upper frequency limit is met when neighboring atoms,
assuming the linear chain model, oscillate with a 1808
phase shift, the so-called optical branch of oscillations in
a solid (115).
ULTRASONIC.
ULTRASONIC IMAGING
OLIVER KRIPFGANS
University of Michigan
Ann Arbor, Michigan
INTRODUCTION
Sound Waves
Sound waves are mechanical waves by nature and a medium is needed to carry them. These spatialtemporal oscillations occur nonsynchronously throughout a medium and
cause density fluctuations, which in turn cause temperature oscillations if the rate of such fluctuations is larger
than the time constant for thermal equalization. Typical
properties to describe sound waves are
Displacement s s(t) of a particle due to a traversing
wave
Sound particle velocity dtd s dtd st vt
Instantaneous mass density r r(t)
Instantaneous pressure p p(t)
where the later most is the deviation from the ambient static
pressure. Mechanical properties, such as strain tensor sij
and stress tensor sij can be used to develop relationships
between the above mentioned properties of sound waves
(Fig. 1).
For mostly lossless media, such as water, one can use
the laws of conservation of momentum and conservation of
mass to derive the wave equation for sound waves,
1 @2
B
@c
@c
r pr 2 2 pr
const
const
(1)
A
@
p
@T
c @t
T
p
PHYSICAL PRINCIPLES
454
ULTRASONIC IMAGING
sxy
s xx
s xz
dx
Quantifying Sound
s ii =
s ij
dy
=
+
x y
d
dx
planar waves
spherical waves
(3)
Z p=U z=S
Zm f =U
x or r
Figure 2. Illustration for the general solution of equation 1; two
traveling waves F and G in opposing directions, r and r,
respectively.
Zr Z=S
Acoustic impedance
Mechanical impedance
ULTRASONIC IMAGING
For these two special cases one can see that planar
waves have pressure (p) and particle velocity (v) in phase.
The ratio of pressure to velocity is a real number and is
constant (r0 c). Spherical waves, however, behave differently. Pressure and particle velocity are out of phase when
measured close to the sound source. The ratio of pressure to
velocity is a complex value (due to the ejy term and cot y kr)
and it changes with distance (r). For large r, the spherical wave
solution approaches the planar wave solution, that is, when
kr 1.
The parameter Z, the acoustic impedance, is often
referred to as a frequency independent constant. The
importance of this property lies in the nature of ultrasound.
When imaging the human body, the sound waves travel
through many layers of varying impedances, such as skin,
fat, connective tissues, and organs. The crossing of each
tissue boundary changes the sound waves in several ways.
Typically, sound both transmits and reflects from tissue
layers. While sound is mostly transmitted, small reflections are recorded and displayed as gray levels in a socalled B-mode image, where larger amplitudes of reflected
waves is displayed as brighter pixels. More complicated
scenarios include mode conversion between longitudinal
and transverse waves. Reflection and transmission coefficients for pressure are directly related to the change in
acoustic impedance as given in the following equation:
R
Z2 Z1
Z2 Z1
2Z2
Z2 Z1
1RT
(8)
455
pi (x, t) = p0 e ik ( x ct )
p t(x, t) = T p 0 e ik ( x ct )
p r(x, t) = Rp 0 e ik ( x + ct )
Z1
Z2
absorption, or scattering. Reflection is caused by impedance changes, whereas absorption and scattering occur
due to the internal structure of the medium. Viscous
forces cause sound absorption following LambertBeer
Bouguers law
dI bIdx
Ix; b Io ebx
(9)
px; t px 0; t eikxctiki x
where ki is imaginary, and therefore p(x, t) decays exponentially for x >0. In general, acoustic waves in medical
imaging are attenuated by traveling through layers of
different tissues due to reflection and also due to attenuation inside tissue. Typical acoustic attenuation in biological tissues is of the order of 0.11.0 dB MHz1 cm1, that
is, a acoustic wave of 1 MHz center frequency, which
travels 0.5 cm deep into tissue (1 cm round trip), is diminished by 0.11.0 dB, or its amplitude is reduced by
1
11%. However, a 2.25 MHz wave penetrating the abdomen
to a depth of 15 cm at 0.7 dB MHz1 cm1, will be amplitude attenuated by 47.25 dB or 99.6%. Good ultrasound
systems have signal to noise and amplification capabilities
up to 120 dB, and therefore allow penetration to a reasonable depth at megahertz frequencies. Typical frequency
selections are 7.515 MHz for 13 cm depths and 2.25
3.5 MHz for 1215 cm depths.
PulseEcho
Most medical imaging via ultrasound uses a pulseecho
method to obtain images. That is, sound waves are transmitted into the body and echoes from within the body are
registered, and their origin is computed using complex
algorithms. Pulseecho is somewhat unique to ultrasonic
imaging. Other modalities use transmission (X ray and CT)
or register preexisting radiation from within the body
(PET, SPECT).
Multiple transmissions at the same physical location
can reveal the motion of targets. A fundamental assumption is the speed of sound in the investigated volume.
Typically, water is assumed to be 1485 m s1, and human
tissue varies between 1450 and 4080 m s1 (see Table 1),
with an average soft tissue value of 1540 m s1 (6). In
general, the speed of sound is inversely related to the
compressibility K (m2 N1) and mass density r (kg m3)
456
ULTRASONIC IMAGING
Tissue
Air
Fat
Human tissue
(mean)
Mean Velocity,
m s1
330
1450
1540
Tissue
Mean Velocity,
m s1
Brain
Blood
Skull bone
1541
1570
4080
Water
1485
See Ref. 6.
(c)
+1
0
-1
(b)
3 particles
t = 32.5 s
+1
(a)
0
-1 t = 26 s
20
1
c p
rK
t = 39 s
25
30
(10)
35
40
45
Time (s)
Density
Relative permitivity
Elastic modulus
Piezoelectric constant
Units
3
gm
e/e0
1010N m1
1013C N1
Coupling constant
Speed of sound
Characteristic impedance
m s1
MRayl
55
60
Table 2. Piezoelectric Properties of Typical Materials Used for Fabrication of Ultrasound Transducers
Property
50
PVDF
PZT5A
Quartz (x-cut)
1.78
12
0.3
d31 20
d33 30
0.11
7.6
1700
4.9
d31 180
d33 360
k31 0.35
k33 0.69
4400
2.6
4.52
5740
15.2
ULTRASONIC IMAGING
Elongation:
elec. potential
Compression:
rev. elec. potential
(a)
Axial
distance [cm]
Neutral:
no stress
Elevational 0
distance [cm]
0
2
Axial
(b)
Figure 5. A piezoelectric crystal exhibits an electric charge on
its surface when under mechanical stress (shown as the
elementary cell response). The reverse effect is used to
produce ultrasound; applying an alternating electrical
potential across a piezoelectric crystal causes the crystal to
vibrate along a given direction.
457
Kerf (k)
Lateral
distance [cm]
Pitch (p)
aw
p
ln
a
ln
yg arcsin
p
ys arcsin
n 2 N0
(11)
458
ULTRASONIC IMAGING
0
Grating lobes
(a)
fwhm 2.8 mm
20
40
60
Side lobes
2
fwhm 1.2 mm
(b)
20
40
60
from the center of the transducer and the line from the
center to the observation point, t is time, r is the mass
density of the surrounding water, c is the speed of sound in
water, U0 is the sound particle velocity on the aperture, and
o and k are angular frequency and wave number, respectively.
The integral is simplied for circular geometry and taken over
the entire surface of the transducers aperture. In real world
simulations, one could take into account that the circumference
of the aperture might be clamped or for other reasons not be
able to oscillate with the same amplitude as the center of
the aperture. To do so, one would keep U0 inside the integral
as a function of radius or even radius and in-plane angle of
the aperture.
Z
Q u ndS
(12)
S
P1 P2
Ps
) Pp
Qp
Q1 Q2
Qs
Z
rc
Pp
u ndS
i2lr S
Z ikp
r2 s2
ircU0 ivt
e
p 2psds
e
P p r; y; t
r
r2 s2
S
(13)
After deriving the general pressure field, one can compute special cases that are of particular interest, such as
the central axis, as well as the far-field angular distribution
of the radiation pattern. Further simplification of Eq. 13
yields approximate expressions for both cases and plots are
shown in Fig. 8.
p
2
2
pr; 0; t rcU0 eikx eik x a eivt
central axis
pr a; y; t
ir cU
2J ka sin y
0 0 akaeivtkr 1
ka sin y
2r
far field
14
From the axial dependence one can see strong interference for locations close to the transducer surface. This
region is called near the field or Fresnel region and it
extends approximately r 4 aperture diameters a away
from the transducer. Beyond that point, the pressure
falls off following a 1/r dependence, and this region is
called the far field or Fraunhofer region. As a rule of
thumb, the far field starts at a2(2 l). Imaging is impractical or impossible in the near field. However, one should
keep in mind that this result is true only for a single
element transducer, and subdividing the aperture into
an array of small elements shifts the near-fieldfar-field
transition toward zero based on the actual dimension of
the array. Moreover, this transition point is also a function of the emitted frequency as represented by angular
frequency and wave number in Eq. 13 and 14. For illustration purposes, a ka value of 8p was chosen for Fig. 8a.
When plotting the angular field pattern in Fig. 8b. However, ka 4p was chosen to reduce the number of sidelobes
and make the plot more readable. Similarly to Fig. 7, a
strong main lobe and additional side lobes are evident in
Fig. 8b, that interfere with the main lobe in the sense that
appreciable sound will be detectable in nearly all directions. In fact, for this particular example echo amplitudes
ULTRASONIC IMAGING
(a)
P / 2 0 c U0
0.8
0.6
0.4
Fresnel
region
0.2
0
2
60
r/a
45
Fraunhofer
region
4
6
30
(b)
15
0 dB
-6 dB
-12 dB
459
Single element
Mechanical
sector scanner
Figure 8. Acoustic field of a circular single element ultrasound
source (transducer). (a) The axial transducer response can be
divided into near field and far field, with an asymptotic 1/r
dependence for large r. Phase interference is dominating in the
near field. (b) Angular radiation patterns are described by the
Fourier transform of the aperture function. A circular piston
transducer yields a function that is defined as a Bessel function
of the first type divided by its argument [J1(x)/x].
Time window
for range gating
60708 off the center axis will be only 50% lower than the
main lobe. Note that this example is for educational purposes and is not at all a suitable design for imaging.
Aperture sizes and frequencies as shown in Fig. 7, where
a narrow and dominant main lobe can yield lateral and
elevational spatial selectivity and time range gating, can
yield depth information. In general, radiation patterns can
be derived as Fourier transforms of the emitting aperture.
Circular apertures are described by Bessel functions of the
first type divided by their argument, that is, J1(x)/x. For
rectangular apertures the sine function [sin(x)/x] directly
describes the field.
ACOUSTIC IMAGING
Ultrasonic imaging yields 2D images. Pixel columns represent the lateral extent and rows of pixels display reflections
of the transmitted acoustic waves from progressively deeper tissues within the body.
The most rudimentary way of obtaining lateral image
data is done by using a single element transducer and
wobbling it back and forth over a chosen sector. The most
elegant way is to use an electronically controlled array of
very small transducers and scanning and or steering an
imaging beam across the region of interest. The former
460
ULTRASONIC IMAGING
No phase delays
To render an image, a subaperture is formed and linearly moved through the whole physical aperture. A major
drawback of this imaging scheme is the dead time of the
scanner, which occurs while waiting to receive the backscatter from the maximum depth. Fifteen centimeters of
penetration require a wait time of at least (two fold for the
round trip time):
0:15 m
t
2 200 ms
1540 m s1
In addition to this delay, some additional wait time may
be required to suppress echoes from even larger depths.
Image lines might be separated by 250 mm. For a physical
aperture of 5 cm, for example, one has to transmit and
receive 201 scan lines, which is equal to a time of 200 ms
201 lines, that is, 40.2 ms per one full frame or a frame rate
of 25 Hz. This frame rate seems reasonable, but one has to
keep in mind that no extra wait time was added nor any
other imaging overhead such as occurs during blood flow
imaging using Doppler.
Nonetheless, if one takes into account the finite lateral
width of a transmitted wave, one can subdivide the total
image width into independent image segments in which
beams can be fired simultaneously, or at least with minimal delay (see Fig. 11). Therefore an aperture of 5 cm could
eventually be imaged with five simultaneous beams or a
fivefold higher frame rate. Such high frame rates allow
real-time ultrasonic imaging of the body and additional
overhead, such as is mentioned above for Doppler or multizone focusing. This type of focusing is used when a large
depth image would cause the acoustic beam to diverge too
much before and after the focal point. By firing the same
image line two, three, or four times, the same number of
foci can be formed for tighter acoustic beams at larger
depths or for shallow regions. This scheme will work to
the limit that the beams are not overlapping, that is, there
is no signal coming from adjacent image lines.
Other imaging modalities, such as X ray, do not suffer
from slow acquisition time due to low wave speeds. Another
method to overcome the speed of sound limitation is the use
Order
of
firings
...
1 4 7
...
2 5 8
...
3 6 9
Acquired
B-mode
image
ULTRASONIC IMAGING
461
462
ULTRASONIC IMAGING
Imaging array
Blood vessel
with moving scatterer
p(t) = p 0 e it
v(r,t)
vtcos aDt
vt
vDt 1 2
l
c
(15)
ULTRASONIC IMAGING
lim
dt
dt
p e ! 0 1 t t
te t t
463
c d
ft
2v0 dt
(19)
(18)
Figure 16. Pulse wave Doppler example. See text for more
description.
464
ULTRASONIC IMAGING
vn t c
cos a
v0 Tre p 2
(20)
Figure 17. Color flow example showing blood flow in the carotid
artery. The color data (here in gray scale) encodes magnitude and
direction of flow. A color bar allows the quantitative conversion to
actual speed, here a maximum of 23 cm s1.
ULTRASONIC IMAGING
3D Imaging
N1
Sn1
QnIN n InQN n
N1 2
iSn1
Q n I 2 n
c
arctan f
2v0 Tre p
(21)
Power Doppler
The previous two methods of flow quantification suffer
from a lack of good flow detection. In perfusion studies, it is
often necessary to detect very small amounts of flow
volume travelling through capillaries at velocities of the
order of 1 mm s1, which is 0.1% of the speed observed in
the carotid artery. In order to overcome the poor sensitivity of PW and CF Doppler, power Doppler displays the
integral of the power spectrum P(w), shown in Eq. 20.
Typically, the integration value is also averaged over a
very long period of time (several heart beats). Averaging at
least one cardiac cycle results in a nearly constant value
for flow. Physically, this value represents the amount of
blood flowing, but not the velocity, since it is the integral of
all detected velocities.
First, imaging capillary flow yet remains difficult, even
in power Doppler mode, partially because blood cells do not
scatter much of the transmitted acoustic signal. Small
blood vessels, such as the capillaries, provide small fractional blood volume, which further decreases the total
backscattered signal. Second, at 1 mm s1, flow velocities
in capillary beds are difficult to differentiate from static
soft tissue background at zero frequency shift, without
being suppressed by the wall filter. This filter is used to
prevent tissue motion from being incorrectly ascribed as
real flow. In Fig. 17 flow that causes <71 Hz frequency shift
per Doppler firing is filtered out of the Doppler data to
eliminate flow speeds of <x cm s1.
The ultrasound machine transmits Doppler pulses
every 0.42 ms (recipocal of 2.4 kHz). Backscatter will contain phase shifts between p and p, which corresponds to
23 and 23 cm s1 flow speed.
The acoustic wavelength of the color Doppler (CF panel
on the right side in Fig. 17) transmits equals 0.385 mm in
tissue (c 1540 m s1, Frq 4 MHz, l c/Frq) and each
firing is separated 0.42 ms (recipocal of PRF 2.4 kHz).
The Doppler electronics measures phase shift, therefore
it can not measure more than a shift of 2p or p. Two-pi
corresponds to l or p to l/2, hence the maximum
detectable speed of v s/t 45.8 cm s1, with s l/2 and
t 1/PRF. However this value does not match the displayed 23 cm s1. Doppler pulses work in pulse-echo mode,
in which any displacement dx results in a time shift of 2times dx/c. Finally the maximum detectable flow speed is
given by equation 22. For a given wallfilter (WF) the
minimal detectable flow is given by the ratio of the PRF
to wall filter times the maximum flow, that is, (2.4 kHz/
71 Hz) 23 cm s1 0.68 cm s1.
Current ultrasound images are naturally 2D because ultrasound imaging arrays are only 1D. One-dimensional arrays
are still predominant in the market. Even so, great efforts
in the ultrasound community are pushing ultrasonic imaging toward 2D arrays. The transition from 1D to 2D is
especially apparent in the naming scheme of current
arrays:
1D: Is the classic linear or focused array, which has one
row of elements that allows focusing and steering in
the lateral imaging plane. The elevational focus is
constant due to a fixed elevational curvature of each
element.
1.25D: Extra rows of elements on either side of the main
row allow changes in the elevational aperture, but
there is no electronic elevational focusing, nor steering.
1.5D: This class of arrays has a 2D set of elements,
where the elevational elements are connected symmetrically to the center row. This array can focus in
the elevational direction but not steer.
1.75D: A 2D set of individually driven elements is
available for this type of array, but the number of
elements in the elevational direction is much less
than in the lateral direction. Elevational focusing is
possible, but only limited elevational steering is
available.
2D: Elevational and lateral directions should be equivalent and indistinguishable for a true 2D array. Full
apodization, steering, and focusing is possible in 3D.
Currently there are some commercial systems that
use 2D arrays particularly in cardiac imaging.
Hardware and software implementations allow the 3D
reconstruction of a scanned volume even when using 1D
arrays. Sophisticated 3D hardware position sensors allow
ultrasound scanners to register the position and orientation of a 1D array in 3D space. Therefore, any acquired
image in a set of many can be aligned with others in the
set to render a 3D volume (see Fig. 18). However, these
hardware additions are costly and can be inconvenient.
Moreover, they might show limitations due to interference
with electromagnetic fields or nearby metallic objects. Software solutions use correlations between adjacent image
frames to determine the transducer translation or rotation. Figure 18 rudimentarily illustrates how individual
frames taken in freehand fashion are stitched together to
form a 3D volume, which can be rendered in various ways.
Figure 19 shows an anatomical example of the bifurcation
of the ascending carotid aorta rendered as a 3D volume.
Some implementations on clinical scanners, however,
already use the 4D nomenclature by adding time as the
fourth dimension.
CONTRAST IMAGING
dt
1=PRF
1=2:4 103
23 cms1
465
22
466
ULTRASONIC IMAGING
Freehand
scanned images
Created 3d
image volume
Correctly aligned
freehand images
Readout or display
3D volume
imaging. However, a limited number of clinical applications is approved by the Food and Drug Administration
(FDA). As of 2004, the only FDA approved application for
ultrasound contrast agents is for cardiac procedures, and
more precisely, for outlining the border of the heart chamber. Other countries or regions such as Europe and Japan
have a variety of agents approved. However, considerable
research has been performed on ultrasound contrast
agents, and it is likely that more FDA approvals will follow
in the future. Contrast agents are used to enhance ultrasound image quality; therefore, imaging techniques implemented in current ultrasound scanners will be described.
I2 I1
I1
(23)
The key for contrast improvement for ultrasonic contrast agents lies in the physical principles of sound transmission, reception, and the nonlinear characteristics of
bubbles themselves. For example, an increase in backscatter amplitude in the presence of contrast agents relative to
the average human tissue backscatter level would improve
the overall image. Furthermore, the creation of acoustic
frequencies that occur in the backscatter signal of bubbles
but not in the transmit signal nor in the backscatter of
tissue, would provide a mechanism by which bubbles can
improve the overall image. An important fact to keep in
mind is that ultrasound contrast agents do not enhance the
visibility of human tissue nor of blood, but the bubbles
themselves can be visualized better than tissue or blood.
Nevertheless, imaging perfusion of tissue or measurement
of the amount of blood flowing through a vessel can be
greatly improved by the usage of ultrasound contrast
agents.
Modern Agents. Modern agents are not just gas bubbles. A sophisticated shell coating is used to prevent coalescence and reduce diffusion of the interior gas into the
surrounding medium. This shell can be made of serum
albumin. Lipids are also used as stabilizing agents. The
gases filling the interior of the shell are chosen for low
diffusion rates from the bubble into the blood stream as
well as because of their low solubility in blood. Table 3 lists
commercially available contrast agents. Currently FDA
approved contrast agents include Imavist by Alliance
Pharma/ Photogen, Definity by Bristol-Myers Squibb Medical Imaging Inc., Albunex by Molecular Biosystems, and
Optison by GE/Amersham.
ULTRASONIC IMAGING
467
Agent Name
Interior Gas
Shell Material
Acusphere
Alliance Pharma. / Photogen
Bracco
Bristol-Myers Squibb Medical Imaging, Inc.
Al-700
Imavist
SonoVue
Definity
MRX-815-stroke
Albunex
Oralex
Optison
Sonazoid
Echovist
Levovist
EchoGen
SonoGen
Perfluorocarbon
Perfluorohexane, air
Sulfur hexafluoride
Perfluoropropane
Perfluoropropane
Air
Air
Perflutren
Perfluorobutane
Air
Air
Dodecafluoropentane
Copolymers
Surfactant
Phospholipid
Lipid bilayer
Lipid bilayer
Albumin
Dextrose
Albumin
Lipid
Galactose
Lipid layer
Albumin
Charged surfactant
Molecular Biosys.
GE/ Amersham
Nycomed Imaging AS
Schering AG
Sonus Pharma.
a
(25)
3 2r r0
3k
The first term represents a monopole type bubble
oscillation, whereas the second term describes a dipole
term. One can see that the monopole term dominates
the scattering due to the large compressibility (k) difference between water and airgas. Density differences
(r) between water and air/gas are large too, however, the
monopole term dominates the acoustic scattering (see
Table 4).
Mathematical and Physical Modeling. The equation of
motion of a bubble can be readily derived from an energy
balance of kinetic (T) and potential energies (U) using the
Lagrange formalism (L T U). It should be mentioned
that the momentary inertial mass of the bubble as an
oscillator does change with time. This is a major reason
why ultrasound contrast agents are nonlinear systems, as
Material
Water
Air
Bulk
Modulus
k, MPa
2250
0.14
Density
r, kg m3
1000
1.14
Monopole
Magnitude
0
2.9 107
Dipole
Magnitude
0
0.33
468
(a)
ULTRASONIC IMAGING
p [k?&]
(b)
transmitted pulse
40
p [dB] for p T
(re p incident)
20
10
38 40 42 44 46 48 50
= 1 kPa
3
f [MHz]
20
t [s]
30
20
40
40
round peaks
(c)
r [m]
4
(d)
for p T = 50 kPa
3.5
38 40 42 44 46 48 50
2.5
t [s]
p [dB] for p T
(re p incident)
60
70
80
100
110
120
= 50 kPa
f [MHz]
sharp peaks
Figure 20. For higher transmit sound pressures (pT) gas bubbles
exhibit nonlinearities at similar magnitudes as the fundamental
frequency [(b) vs. (d)]. Higher harmonics increase in their relative
amplitude with sound pressure. Radials oscillations of the gas
bubble contrast agent shows the nonlinear response during the
compressional phase (arrows at small radii). Harmonic imaging
takes advantage of the strong nonlinear character of contrast
agent, which can be stronger than tissue depending on the
number density of the bubbles.
ULTRASONIC IMAGING
First pulse
Second pulse
Sum
(a)
(a) Linear
response
of tissue
transmitted pulse
(b)
p [ kPa]
r [mm]
40
3.2
10
15
20
25
t [ms]
14 16 18 20 22 24 26
2.8
(c)
(d)
for pT = 50 kPa
for pT = 50 kPa
r [mm]
r [mm]
3.4
3.2
3.1
3.2
t [ms]
2.9
40
(b) Nonlinear
response
of a bubble
for pT = 1 kPa
3.1
20
20
469
10
15
20
25
t [ms]
14 16 18 20 22 24 26
2.8
2.9
2.6
2.8
t [ms]
470
ULTRASONIC IMAGING
Sum of 1st & 3rd
has (0+10)/2=5
phase (S1)
1st pulse
0
add
0 + 10
signal
Time
5+180
add S1 with S2
3rd pulse
10
signal/noise ratios is to increase the amplitude of transmitted sound. However, the FDA regulates sound pressure
amplitudes because of the likelihood of acoustic cavitation
in the presence of large sound pressure amplitudes. Moreover, the number of acoustic transmissions per unit time
(pulse repetition interval, PRI) as well as the length of
individual pulses (burst length) are regulated by means of
the overall deposited energy that will eventually result in
tissue heating. Both effects will be discussed in the Bioeffects section below. In addition to regulatory and safety
concerns, increasing the number of cycles in a traditional
transmit pulse also reduces the axial resolution.
However, improvements in signal to noise ratios without sacrificing axial resolution can be achieved despite
regulations on pressure amplitudes and burst lengths.
Transmission of specially designed and unique signals
can significantly improve their detectability. This concept
is called Coded harmonic excitation.
Various code types shall be discussed here to illustrate
how Coded excitation works. Figure 25 illustrates two
codes. On the left side is the most simple code, a so-called
pulse train (or uncoded tone burst), that is, a series of
pulses or sinusoids. When transmitting four cycles at a
certain frequency one can use a frequency filter that is
sensitive at the transmit frequency, but only for signals
that are four cycles long. A more complicated type of coded
excitation is the code shown on the right side of Fig. 25.
This signal also transmits four cycles, but now the four
cycles all differ in sign as well as in amplitude. Both
features make this code more unique and therefore more
detectable when ambient noise lowers SNR.
Above mentioned frequency filters are explained in
Figs. 26 and 27. The first column in Fig. 26 illustrates
the transmit pressure waveforms and the second column
shows the receive filter used. A mathematical technique
termed convolution is used to match the transmitted waveform with the anticipated receive signal by means of an
appropriately designed filter. The average reader might
not have adequate signal processing background to be
familiar with this concept. Therefore, Fig. 27 will be used
to explain Coded Excitation for the example of Golay code
Filter
Filtered
signal
amplitude
time
Filter A
Filtered
signal A
Golay coded
receive signal
Golay code B
Filter B
Filtered
signal B
Matching filter
Matching filter
ULTRASONIC IMAGING
1
-1 1 1 1
-1 1 1
-1 1
-1
1
1 -1 1 1
1 -1 1
1 -1
1
1 1 -1
mu
ltip
ly
1
1 1
*
1 1 1
-1 1 1 1
-1 1 1 1
-1 1 1 1
1 -1 1
1
1 1
-1 1 1
1 -1 1 1
1 -1 1 1
1 -1 1 1
1
0
3
-2
1 =Y
471
TI
W pNm s1
W1o Nm s1
(27)
472
ULTRASONIC IMAGING
(28)
2
Peripheral vasculature
Cardiac
Fetal and other
Ophthalmic
a
ISPPA.3,
mW cm2
720
430
94
17
ISPTA.3,
W cm2
190
190
190
28
MI
1.9
1.9
1.9
0.23
ACKNOWLEDGMENTS
I wish to thank Katy, Kim, Mario, John, and Jessi for their
invaluable efforts for proof reading and their technical
comments. Also, I would like to thank the reviewers for
their contributions and very helpful commentary. Most of
all, I wish to thank my wife Naki for her patience during
many lost hours of family time.
BIBLIOGRAPHY
1. Angelsen BAJ. Ultrasound Imaging Waves, Signals, and
Signal Processing; 2000.
2. Averkiou M, et al. Ultrasound contrast imaging research.
Ultrasound Q 2003;19:(1):2737.
3. Becher H, Burns PN. Handbook of Contrast EchocardiolographyLV Function and Mycardial Perfusion. Berlin:
Springer-Verlag; 2000.
4. Church CC. The effects of an elastic solid surface layer on the
radial pulsations of gas bubbles. J Acoust Soc Am 1995;
97(3):15101521.
5. deJong N, et al. Absorption and scatter of encapsulated gasfilled microspheres: Theoretical considerations and some
measurements. Ultrasonics 1992;30:95105.
6. Duck FA. Physical Properties of Tissue. San Diego: Academic
Press; 1990.
7. Feinstein SB. The powerful microbubble: From bench to
bedside, from intravascular indicator to therapeutic delivery
system, and beyond. Am J Physiol Heart Circ Physiol
2004;287: H450H457.
8. Gray H, Williams PL, Bannister LH. Grays anatomy: The
anatomical basis of medicine and surgery. New York:
Churchill Livingstone; 1995.
9. Grayburn PA. Current and future contrast agents. Echocardiography 2002;19(3):259265.
10. Hoff L. Acoustic characterization of contrast agents for medical ultrasound imaging. Ph.D. dissertation at the Norwegian
University of Science and Technology in Trondheim, Norway;
2000.
11. Holland CK, Apfel RE. Thresholds for transient caviation
produced by pulsed ultrasound in a controlled nuclei environment. J Acoust Soc Am 1990;88(5):20592069.
12. Kasai C, Namekawa K, Koyano A, Omoto R. Real-time twodimensional blood flow imaging using an autocorrelation
technique. IEEE Trans, Ultrasonics, Ferroelectrics, Frequency Control 1985;SU-32(3):458464.
13. Li P, Cao et al. Impact of myocardial contrast echocardiography on vascular permeability: An in vivo dose response
study of delivery mode, pressure amplitude and contrast
dose. Ultrasound Med Biol 2003;29(9):13411349.
14. Li P, Armstrong WF, Miller DL. Impact of myocardial contrast echocardiography on vascular permeability: Comparison of three different contrast agents. Ultrasound Med Biol
2004; 30(1):8391.
15. Lindsay RB. The story of acoustics. J Acoust Soc Am 1965;
39(4):629644.
473
INTRODUCTION
It is to the philosophers and physicians of the ancient
civilizations that we should attribute the earliest history
of ultraviolet radiation (UVR) in medicine (1). For example,
the Greek sun god, Apollo, was also the spiritual god of
healing, providing the first documentation of an association between sunlight and health. In 525 BC, Herodotus
observed that the strength of a humans skull was related
to sunlight exposure, >2000 years before the formal discovery of the role of sunlight in vitamin D metabolism. At
about the same time the Egyptians were using psoralens
from plant extracts and sun exposure in the treatment of
vitiligo. However, it was not until Jonathan Ritter in 1801
discovered the UV region in the solar spectrum that the
science of photobiology could really begin.
The Danish physician Niels Finsen (18601904) is
regarded by many as the father of modern UV therapy.
In a series of articles published between 1893 and 1896,
474
Ultraviolet radiation is part of the electromagnetic spectrum and lies between the visible and the X-ray regions.
Different wavelengths in the UV spectrum show enormous
variations in ability to cause biological damage, and for this
reason the UV spectrum is divided into three spectral
regions: UVA, UVB, and UVC. The notion to divide the
UV spectrum into different spectral regions was first put
forward at the Copenhagen meeting of the Second International Congress on Light held during August 1932. It
was recommended that three spectral regions be defined as
follows:
UVA 400315 nm
UVB 315280 nm
UVC 280100 nm
The subdivisions are arbitrary and differ somewhat
depending on the disciplines involved (3). The boundary
between UVA and UVB is sometimes set at 320 nm and
that between UVB and UVC is sometimes regarded as
290 nm. The short wavelength limit for UV is sometimes
quoted as 100 nm and sometimes as 200 nm. The UVA
region has recently been divided into UVAI (340400 nm)
and UVAII (320340 nm).
Due to potential confusion with this terminology and
because of rapidly changing biological effects as a function
of wavelength, it is recommended that, in publications in
photobiology, bandwidths are quoted explicitly and ideally
the full spectrum of UV sources is described.
10
Skin
Type
Skin
Color
Sensitivity
to Sunburn
Ability
to Tan
Skin Cancer
Risk
I
II
III
IV
V
VI
White
White
White
Olive
Brown
Black
Very high
High
Medium
Low
Very low
Very low
Virtually nil
Poor
Good
Very good
Very good
Very good
High
High
Medium
Low
Very low
Very low
300
350
400
Wavelength (nm)
Relative effectiveness
% transmission
100
1
250
475
10
0.1
0.01
0.001
0.0001
0.00001
250
300
350
400
Wavelength (nm)
Figure 3. Standard action spectra for erythema (9), nonmelanoma skin cancer (10), and UV hazard (6).
Incandescent Sources
Incandescent sources emit a smooth broad spectrum of
radiation with the peak wavelength inversely related to
the absolute temperature. Conventional tungsten bulbs
used for domestic lighting have peak emission in the
infrared (IR) region and emit very little UVR. Tungsten
halogen bulbs operate at higher temperatures and may
produce rather more UVR. These sources are not used for
medical applications due to the low UV output, although,
they may be used as reference sources for UV meter
calibration.
Mercury and Metal Halide Arc Lamps
The radiation emitted from a mercury-vapor arc lamp
arises from two mechanisms. Line or characteristic radiation is produced as a result of excitation of the constituent
atoms, together with a spectral continuum that is chiefly
due to ion and electron recombination. Lamps can be
produced that operate at different pressures. A low pressure mercury arc lamp consists of a fused silica tube filled
with argon at
1 Pa and containing a drop of mercury. A
discharge occurs between the electrodes sealed into the
ends of the tube. More than 90% of the radiant energy
produced by the discharge is at 253.7 nm. Various other
characteristic mercury spectral lines occur, for example, at
313 and 365 nm, and these sources are useful for wavelength calibration of spectroradiometers.
If the pressure in the lamp tube is increased, then the
spectral lines broaden and also more radiation occurs in the
continuum (see Fig. 4). The alpine sunlamp is a type of
medium pressure arc lamp that was widely used for phototherapy, but has since been superseded by fluorescent
lamps. The addition of metal halides to a high pressure
mercury discharge lamp greatly enhances the UV output.
These lamps were common in phototherapy departments
at one time, but have now been mostly replaced by fluorescent UVB lamps. These lamps are still occasionally used
for cosmetic tanning. By incorporating optical filters
between the lamps and the irradiated subject, absorption
of the UVC or UVC and UVB components can be achieved
(see Fig. 5).
Relative irradiance
476
1.0
Medium pressure mercury
0.8
0.6
0.4
0.2
0.0
250
300
350
400
Wavelength (nm)
477
1.2
0.4
Relative irradiance
Relative irradiance
UVC+UVB filter
UVC filter
Unfiltered
0.2
1.0
TL10
Performance
Natural
TL09
0.8
0.6
0.4
0.2
300
0.0
350
400
Wavelength (nm)
250
300
350
400
Wavelength (nm)
Relative irradiance
0
250
1.0
0.8
TL01
UV6
TL12
0.6
0.4
0.2
0.0
250
300
350
400
Wavelength (nm)
Relative irradiance
478
10
Term
Unit
Wavelength
Radiant energy
Radiant flux
Radiant intensity
Radiance
Nanometer, nm
Joule, J
Watt, W
Watt per steradian, W/sr
Watt per square meter per
steradian, W/m2/sr
Watt per square meter, W/m2
Joule per square meter, J/m2
1
0.1
Solar
Filtered Xenon arc
Arimed B
0.01
Irradiance
Radiant exposure
(often referred to as dose)
0.001
0.0001
250
300
350
400
Wavelength (nm)
1000 doseJ=cm2
60 irradiancemW=cm2
Weighted Irradiance
It is useful to derive quantities by weighting the spectral
irradiance by an appropriate action spectrum. The erythemally effective irradiance Eeff, is defined as
X
slElDl
Eeff
Where s(l) is the CIE erythemal action spectrum (8), E(l)
is the measured spectral irradiance, and Dl is the bandwidth of measurement. The Global UV index (21) can be
used as a standard way of expressing the erythemally
weighted solar irradiance. A measure of the integrated
effective irradiance received is given by the Standard
Erythemal Dose (SED) (9). One SED is equal to an effective
dose of 100 J/m2. In the past, some have used the MED as a
standard measure of erythemal dose. However, this is not
correct, MED should be reserved to describe an individuals
erythemal response and not a standard measure of
dose received. The number of SED required to cause just
479
UV Radiometers
A radiometer is a complete UV measurement device, consisting of a detector and a meter to amplify and display the
detector output. Narrow-band UV radiometers are used to
measure the irradiance of a source in the different UV
480
481
Table 3. The Principal Photodermatoses, Main Clinical Features, and Typical Phototest Responses
Condition
Polymorphic
light eruption
Chronic actinic
dermatitis
Provocation Test
Response
Photopatch
Test Response
Positive response
(5080% sensitivity)
at suberythemal doses
n/a
n/a
n/a
n/a
n/a
n/a
n/a
Positive when
chemical is
exposed to UV
n/a
482
0.1
Reciprocal dose cm2/mJ
0.01
0.001
0.0001
250
260
270
280
290
300
310
320
Wavelength (nm)
483
Psoralen Photochemotherapy
This form of treatment, known as PUVA, involves the
combination of the photoactive drug psoralen and UVA
irradiation to produce a beneficial effect. Psoralen photochemotherapy has been used to treat many skin diseases
(43), although its principal success has been in the management of psoriasis. The psoralen may be applied to the skin
either topically (44) or systemically (45); the latter route is
generally preferred. The psoralen is usually administered
as 8-methoxypsoralen (8-MOP). The patient ingests the 8MOP tablets and is then exposed to UVA radiation 1 or 2 h
later when the photosensitivity of the skin is at a maximum. The mechanism of the treatment is thought to be
that psoralen binds to DNA in the presence of UVA,
resulting in a subsequent transient inhibition of DNA
synthesis and cell division. The UVA lamps used for PUVA
therapy (such as the Phillips TL09 or Phillips Cleo Performance lamps) (Fig. 6), typically have a broad spectrum
from
315400 nm peaking at
352 nm. Within the UVA
range, the action spectrum for psoriasis clearance is
thought to be similar to the erythema action spectrum in
psoralen sensitised skin and these peak near 320 nm (46).
A study using narrow-band UVB and psoralen found no
significant difference in response compared to conventional
PUVA treatment (47). It is possible that UVA lamps conventionally used for PUVA treatment do not have the
optimum spectral characteristics. However, narrow-band
UVB phototherapy is now more widely used than PUVA
and there is less interest in pursuing optimisation of PUVA
treatment.
484
485
486
Photopheresis
Photopheresis (also known as extra-corporal photochemotherapy or ECP) was first described by Edelson et al.
in 1987 (78) and its use has recently been reviewed by
McKenna et al. (79) The technique involves the following
process: venous blood is removed from the patient, the
white cells are separated and mixed with 8-mythoxypsoralen, these cells are then irradiated using UVA lamps and
then returned to the patient. A treatment session takes
487
UV Source
Bank of six 4 ft
TL01 tubes
Bank of eight
2 ft TL09 tubes
Single 2 ft
TL12 tube
Single 6 ft
UV6 tube
Xe Arc lamp
a
Weighted Irradiance,
W/m2 Measured with
Spectroradiometer
Weighted Irradiance,
W/m2 Measured
with Radiometer
UVA Unweighted
Irradiance, W/m2
Measured with
Spectroradiometer
Time min to
exceed 104
J/m2 Unweighted
UVA Irradiance,
Eye Hazard
0.43
0.40
45
0.02
0.14
67
30
0.73
1.1
80
0.22
0.26
40
0.20
0.24
70
The weighted irradiance was obtained either by using a radiometer with a hazard weighted filter (International Light IL1730 with ACTS filter) or by
spectroradiometer measurements combined with INIRPC hazard spectrum (6). The times given in the final two columns are those required to exceed to the
maximum permissible exposure for eye and skin calculated from the spectroradiometer measurements.
488
Protection Measures
The National Radiological Protection Board (NRPB) in the
United Kingdom has issued advice on protection against
UVR (5). For workers exposed to artificial sources, administrative, engineering, and protective measures should be
in place to ensure limits are not exceeded. For other
situations, such as members of the public exposed to
the sun, strict observance of limits is not practicable. If
possible, exposure to artificial sources should be limited by
engineering controls. For example, phototherapy cabins
are usually fitted with interlocks so that the lamps go
out when the door is opened. It is essential that staff
working with UV sources are well trained and understand
the nature of UV hazards. Access to suitable trained Medical Physics staff for advice on UV hazards is also important. Warning signs and access restrictions should be used
where exposure above the MPE level is possible. Personal
protective equipment (such as face shield and gloves)
should be used if exposure to UVR above the MPE cannot
be avoided.
The British Standards Institute provide information on
the performance specifications of UV filters for personal
eye protection (87). Percentage UV transmission should be
<0.0003% at 313 nm and <7% at 365 nm and luminous
transmission should be between 43 and 58%.
Patient Safety
Good staff training is vital to minimize risks of patient UV
overexposure during phototherapy. There must be adequate protection against electrical hazards. Patients
should not come into contact with bare lamps. There is a
risk of injury if the patient falls against the lamps and it is
now common practice to place a UV transmitting sheet
between the lamps and the patient.
Because psoralen is deposited in the lens of the
eye, there is a risk of cataract induction if the eye is
exposed to UVA in the 12 h following psoralen ingestion.
Consequently, the patient should avoid unnecessary sunlight exposure for the remainder of the day following
PUVA treatment and they should wear appropriate eye
protection. These may either be sunglasses, prescription
lenses, or clear safety spectacles. Contact lenses even if
marked as UV protective may not afford sufficient protection (88). The suitability of UV protective eyewear may be
assessed using a spectrophotometer to fully characterise
the transmission and comparison with limits suggested by
Moseley et al. (89). Alternatively, a simpler approach (50)
is to measure the lens transmission of radiation from
PUVA therapy lamps using a hand-held narrow-band
meter.
Hazards from Ozone
Ozone is a colorless, toxic irritant gas formed by a photochemical reaction between short wavelength UVR and
oxygen in the air. It is possible to find ozone near UV
lamps, especially where radiation <250 nm is transmitted
through the envelope of the lamp. If ozone production is
suspected, then adequate ventilation should be provided to
remove the hazard.
ACKNOWLEDGMENTS
This article is based on that in the first edition by Prof.
Brian Diffey and certain sections (e.g., the historical introduction) are taken directly from that source. Brian Diffey
provided spectra for some lamps and the skin cancer action
spectrum. Brian Diffey and Peter Farr were both very
helpful in discussing certain parts of the text and providing
useful references. Some of the practical measurements
were made by John Frame. Steve Burnet and Muzz Hanliffa provided some of the pictures.
BIBLIOGRAPHY
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6. International Commission on Non-Ionizing Radiation Protection. Guidelines on limits of exposure to ultraviolet radiation
of wavelengths between 180 nm and 400 nm (incoherent
optical radiation). Health Phys 2004;87(2):171186.
7. Harrison GI, Young AR. Ultraviolet radiation-induced
erythema in human skin. Methods 2002;28(1):1419.
8. McKinley A, Diffey B. A reference action spectrum for Ultraviolet induced erythema in human skin. CIE J 1987;6:1722.
9. CIE. Erythemal reference action spectrum and standard
erythemal dose (CIE S 007/E-1998); 1998.
10. CIE. Report 138/2: Action spectrum for photocarcinogenesis
(non-melanoma skin cancers). Wien: CIE; 2000.
11. Diffey BL, Oliver RJ, Farr PM. A portable instrument for
quantifying erythema induced by ultraviolet radiation. Br J
Dermatol 1984;111(6):663672.
12. Gordon PM, Saunders PJ, Diffey BL, Farr PM. Phototesting
prior to narrowband (TL-01) ultraviolet B phototherapy. Br J
Dermatol 1998;139(5):811814.
13. Waterston K, Naysmith L, Rees JL. Physiological variation in
the erythemal response to ultraviolet radiation and photoadaptation. J Invest Dermatol 2004: 123(5):958964.
14. Diffey BL. The future incidence of cutaneous melanoma
within the UK. Br J Dermatol 2004;151(4):868872.
15. Diffey B. Human exposure to solar ultraviolet radiation. J
Cos Dermatol 2002;1:124130.
16. Diffey BL. Human exposure to ultraviolet radiation. In:
Hawk JLM, editor. Photodermatology. London: Arnold; 1999.
17. Diffey BL. Sources and measurement of ultraviolet radiation.
Methods 2002;28(1):413.
18. World Health Organisation. Intersun, the global UV project;
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19. Hersh P, Carr J. Excimer laser photorefractive keratectomy.
Ophthalmic Practice 1995;13:126133.
20. Anders A, Altheide HJ, Knalmann M, Tronnier H. Action
spectrum for erythema in humans investigated with dye
lasers. Photochem Photobiol 1995;61(2):200205.
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22. Wilson AD. Optical radiation detectors. In: Diffey B, editor.
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44. Halpern SM, Anstey AV, Dawe RS, Diffey BL, Farr PM,
Ferguson J, Hawk JL, Ibbotson S, McGregor JM, Murphy
GM, Thomas SE, Rhodes LE. Guidelines for topical PUVA: a
report of a workshop of the British photodermatology group.
Br J Dermatol 2000;142(1):2231.
45. British Photodermatology Group, British Photodermatology
Group guidelines for PUVA. Br J Dermatol 1994;130(2):246
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46. Farr PM, Diffey BL, Higgins EM, Matthews JN. The action
spectrum between 320 and 400 nm for clearance of psoriasis by
psoralen photochemotherapy. Br J Dermatol 1991;124(5):443
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47. de Berker DA, Sakuntabhai A, Diffey BL, Matthews JN, Farr
PM. Comparison of psoralen-UVB and psoralen-UVA photochemotherapy in the treatment of psoriasis. J Am Acad
Dermatol 1997;36(4):577581.
48. Mackenzie LA. The analysis of the ultraviolet radiation doses
required to produce erythemal responses in normal skin. Br J
Dermatol 1983;108(1):19.
49. Diffey BL, De Berker DA, Saunders PJ, Farr PM. A device for
phototesting patients before PUVA therapy. Br J Dermatol
1993;129(6):700703.
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principles, sources, dosimetry and safety. New York: 1997.
51. Dawe RS. Ultraviolet A1 phototherapy. Br J Dermatol
2003;148(4):626637.
52. Farr PM, Besag JE, Diffey BL. The time course of UVB and
UVC erythema. J Invest Dermatol 1988;91(5):454457.
53. Das S, Lloyd JJ, Farr PM. Similar dose-response and persistence of erythema with broad-band and narrow-band ultraviolet B lamps. J Invest Dermatol 2001;117(5):13181321.
54. Ibbotson SH, Farr PM. The Time-Course of Psoralen Ultraviolet A (PUVA) Erythema. J Invest Dermatol 1999;113(3):
346350.
55. Allan W, Diffey BL. A device for minimizing the risk of
overexposure of patients undergoing phototherapy. Photodermatol Photoimmunol Photomed 2002;18(4):199200.
56. Langmack KA. An insight into the contributions of selfshielding and lamp reflectors to patient exposure in phototherapy units. Phys Med Biol 1998;43(1):207214.
57. Moseley H. Scottish UV dosimetry guidelines, ScUViDo. Photodermatol Photoimmunol Photomed 2001;17(5):230233.
58. Martin CJ, Clouting H, Aitken A. A study of the correction
factor for ultraviolet phototherapy dose measurements made
by the indirect method. Br J Dermatol 2003;149(6):12271231.
59. Currie GD, Evans AL, Smith D, Martin CJ, McCalman S,
Bilsland D. An automated dosimetry system for testing
whole-body ultraviolet phototherapy cabinets. Phys Med Biol
2001;46(2):333346.
60. Evans AL, Martin CJ, Smith DC, Currie GD, McCalman S,
Bilsland D, Dunn S. Instrument for scanning the angular
variation of irradiance in ultraviolet phototherapy cabinets. J
Med Eng Technol 2002;26(3):126131.
61. Autier P. Perspectives in melanoma prevention: the case of
sunbeds. Eur J Cancer 2004;40(16):23672376.
62. McGinley J, Martin CJ, MacKie RM. Sunbeds in current use
in Scotland: a survey of their output and patterns of use. Br J
Dermatol 1998;139(3):428438.
63. Diffey BL, Farr PM. Tanning with UVB or UVA: an appraisal
of risks. J Photochem Photobiol B 1991;8(2):219223.
64. Phillips. Welcome to Phillips Tanning; http//www.lighting.
philips.com 2004.
65. Young AR. Tanning devicesfast track to skin cancer? Pigment Cell Res 2004;17(1):29.
66. Diffey B. Sunbeds: What are they, who uses them and what
are the health effect? London: Health Education Authority;
1997.
490
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
See
V
into account both the structure and function of native
vessels for optimal function.
Normal arteries have three different layers: the internal intima, the middle media, and the external adventitia
(1). (see Fig. 1). The intima is composed of a layer of
endothelial cells, with underlying extracellular matrix
proteins delimited by the internal elastic lamina.
Endothelial cells are responsible for preventing blood
vessel thrombosis under normal physiologic conditions by
preventing platelet adhesion, coagulation, and thrombus
formation (2,3). (see Fig. 2). This is accomplished by the
expression and secretion of antiplatelet agents, such as ectoADPase, prostacyclin (PGI2) and nitric oxide (NO) (2).
Endothelial cells express thrombomodulin (TM) and
release tissue factor pathway inhibitor (TFPI) to prevent
activation of the coagulation cascade. Endothelial cells also
express heparan sulfate to bind circulating antithrombin
and rapidly inhibit local thrombin formation (2). If a fibrin
clot is formed, endothelial cells can release factors that
stimulate the fibrinolytic system to degrade the thrombus,
such as tissue plasminogen activator (tPA) (2). Upon cytokine or thrombin stimulation, endothelial cells can develop a
procoagulant phenotype with expression of tissue factor (TF)
and release of vWf, PAI-1, and coagulation factors (6). The
intima is present in all vessels, with the smallest capillaries
composed of only a single layer of endothelial cells resting
upon a thin basement membrane of extracellular matrix
proteins.
The media varies in composition from large elastic
arteries, such as the aorta, where it is composed of layers
of elastic tissue and glycosaminoglycans to the smaller
muscular arteries, such as the coronary arteries in the
heart, where it is composed predominantly of vascular
smooth muscle cells (1). The elastic and mechanical properties of the media allow vessels to contract or relax to
maintain the lumenal pressure and volumetric flow rate.
Arterioles may have only a single layer of smooth muscle
cells and capillaries have no media at all.
The external blood vessel layer, or adventitia, serves to
supply nutrients to the cells in the blood vessel itself. It
consists of a loose layer of connective tissue, with small
arterioles and capillaries (vasa vasorum or vessels of the
vessel) feeding the blood vessel. It also contains a network
of nerves that can stimulate medial smooth muscle cell
contraction or relaxation. The adventitia is prominent in
larger vessels, becoming progressively smaller as the vessel diameter decreases. Arterioles and capillaries lack an
adventitia completely.
INTRODUCTION
The system of blood vessels in the body is crucial to transport cells, oxygen, and nutrients to the vital organs. When
injured by diseases, such as atherosclerosis, the blood
vessels may become occluded, leading to decreased blood
flow and organ damage, or may be weakened and rupture
due to aneurysmal dilatation. One method of treatment is
to use surgery to bypass diseased blood vessels by using an
artificial blood vessel substitute, or vascular graft prosthesis. Materials currently used in vascular graft prostheses
include polyethylene terephthalate (Dacron) and expanded
polytetrafluoroethyelene (ePTFE). These devices successfully function as vascular grafts in larger diameter applications, but suitable materials for small diameter
prostheses (<5 mm) are still being developed. Current
trends in the development of small diameter prostheses
include surface modification to prevent thrombosis, incorporation of endothelial cells, and a tissue engineering
approach with the development of a biological blood vessel
based upon a biodegradable material scaffold.
THE CLINICAL NEED FOR VASCULAR GRAFT
PROSTHESES
Normal Blood Vessel Anatomy
The largest artery leaving the left ventricle of the heart
is the aorta, which is 20 mm in diameter. The aorta
branches into progressively smaller arteries (<5 mm internal diameter) that feed blood and nutrients to organs, such
as the brain (carotid arteries), liver (hepatic artery) and
kidneys (renal arteries), and to the extremities of the arms
(cephalic arteries) and legs (iliac and femoral arteries). The
smaller arteries branch further to become smaller arterioles (<1 mm), which branch even further to become the
smallest capillaries (<100 mm), through which only single
cells can pass. The capillaries are the site of most oxygen
and nutrient exchange into the tissues. Capillaries then
join together to form venules, small veins, and then larger
veins that carry deoxygenated blood back to the lungs and
heart. The design of replacement blood vessels should take
Coronary Atherosclerosis
Atherosclerotic cardiovascular disease, in its many guises,
is the leading cause of mortality in the United States,
resulting in coronary artery disease, myocardial infarction,
stroke, aneurysms, and peripheral vascular disease. Atherosclerosis is a multifactorial disorder of the arterial vascular tree where lipid dysregulation and vascular
491
492
Antithrombotic
PGI2
NO
EctoADPase
Prothrombotic
PAF
vWF
Platelets
Thrombin
VIIIa/IXa IX VIIa
Protein
S
TM
TFPI
TF
Coagulation
Va/Xa
Prothrombin
tPA
tPA
Fibrinolysis
PAI-1
493
494
Dacron
Dacron is a polyester fabric, polyethylene terephthalate.
Clinically utilized Dacron vascular prostheses are manufactured as textiles, either knitted or woven (34) (Fig. 3).
The original design of a Dacron vascular graft as a textile
versus a solid tube was an attempt to allow tissue healing
of the prosthesis through the pores of the material. The
knitted prostheses have higher porosity than the more
densely fabricated woven prostheses and require preclotting or use of a surface coating, such as gelatin, collagen,
fibrin glue, or albumin, to prevent translumenal leaking
after implantation (34,46,47) (Fig. 4). The woven grafts are
most commonly used in the thoracic aorta and for ruptured
abdominal aortic aneurysms to minimize blood loss (43).
Most Dacron graft prostheses are crimped like a soda straw
to improve graft flexibility and decrease lateral compressibility (Fig. 4). An alternative to crimping that results in a
thinner prosthesis wall is the use of an external spiral
winding of a stiff polymer, such as poly(propylene). In a
495
496
497
Figure 7. Thrombosis of a Dacron vascular graft in the aorta. In such a large diameter prosthesis,
this degree of lumenal thrombosis was of little clinical consequence. A similar degree of thrombosis
in a small diameter vessel could result in complete occlusion.
498
endothelial layer spontaneously, there has been considerable effort expended to develop surface modifications of
ePTFE in particular, in order to encourage growth of a
confluent endothelial layer, subsequent to the initial report
by Herring in 1978 (37).
Two different procedures have been described, endothelial seeding, and sodding. Endothelial seeding involves
treating the graft with a low concentration of endothelial
cells prior to implantation with In vivo expansion of the
cells. A two-stage endothelial seeding technique involves
treating the graft with a low concentration of cells, followed
by extended In vitro culture time to expand the cells to a
confluent monolayer (110,111). Conversely, endothelial
sodding entails coating the graft with a high concentration
of endothelial cells to quickly form a confluent endothelial
layer. The ePTFE is a very hydrophobic material and few, if
any, endothelial cells attach directly to the ePTFE with
either direct seeding or sodding techniques. Without modification, hydrophobic ePTFE grafts show attachment of
only 10 7% of applied cells, with EC retention only 4 3%
(112,113). Surface modification of the ePTFE is necessary
to encourage endothelial attachment and growth. The
source of autologous human endothelial cells can range
from harvested veins, adipose tissue capillaries, and
endothelial progenitors (75,114,115).
Many different surface modifications of ePTFE to promote endothelialization have been studied, such as attaching cell-binding peptides (116) or fibrin glue (117). A few of
these have reached human clinical trials. One such modification involved the application of fibrin glue to the
lumenal surface of a small-diameter ePTFE graft to which
autologous endothelial cells can attach (110,118). These
coated grafts were seeded with autologous endothelial
cells, harvested 46 weeks prior to graft implantation
and expanded In vitro. The seeded graft constructs were
allowed to mature for 810 days before implantation as
either one of 21 coronary artery bypass grafts (110) or 153
infrainguinal grafts (118). After a mean postoperative
follow-up of 27.7 months, the 4 mm diameter coronary
artery graft patency was 90.5%. Angiograms of all 19
patent aortocoronary bypass grafts showed smooth lumenal borders without stenotic regions. Percutaneous translumenal angioscopic evaluation showed a glossy white and
smooth endolumenal graft surface without any fibrin,
platelet, or erythrocyte deposits. The EC seeded grafts
showed an improvement in patency versus unseeded
ePTFE aortocoronary bypass grafts (110). For the 6
7 mm diameter infrainguinal reconstructions, Kaplan
Meier analyses revealed a primary patency rate of 84%
after 4 years and 63% after 7 years, comparable to primary
patency rates for vein grafts (118).
These clinically applied ePTFE modifications were not
without incident. In one trial, In vitro flow experiments
revealed a washout of ECs between 1015% in the first
minute after the application of a physiologic pulsatile flow.
Additionally, one patient had a perioperative MI caused by
the immediate occlusion of the EC-seeded ePTFE graft
because of poor runoff and possible culture contamination
with fibroblasts (110). In the other trial, 5% of patients had
EC that failed to grow in culture despite rescue serum
treatment. At implantation, 5% of seeded grafts were sub-
499
500
501
aneurysms to peripheral arterial disease. Several synthetic vascular graft materials, particularly Dacron and
ePTFE, have been successful as arterial substitutes in
large diameter applications. However, these devices can
fail due to thrombotic occlusion, intimal hyperplasia, and
infection. There is a need to develop novel vascular prostheses that function well in small diameter applications.
Progress has been made on methods to facilitate the incorporation of endothelial cells into vascular grafts. The tissue
engineering approach, with advances in new materials
that can control graft mechanical properties plus cell
attachment and proliferation, holds promise for the next
generation of these crucial medical devices.
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96. Lin P, et al. Small-caliber heparin-coated ePTFE grafts reduce
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98. Walpoth BH, et al. Improvement of patency rate in heparincoated small synthetic vascular grafts. Circulation 1998;98:II
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103. Zhang Z, et al. Vascugraft polyurethane arterial prosthesis
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114. Sharp WV, Schmidt SP, Meerbaum SO, Pippert TR.
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See also BIOCOMPATIBILITY OF MATERIALS; BIOMATERIALS, SURFACE PROPERTIES OF; POROUS MATERIALS FOR BIOLOGICAL APPLICATIONS.
VASCULAR MEASUREMENTS.
505
See PERIPHERAL
See HIGH
FREQUENCY VENTILATION.
VENTILATOR USE
Introduction
A ventilator, like most critical care devices, is simply a
machine. However, it is not a simple machine. Over the
past five decades, the means of delivering gases to patients
have become more complex. This has led to an evolution of
more than 30 critical care ventilators being used in the
United States. The numerous modes of ventilation and our
unfortunate attempt to reach a consensus on the terminology used when referring to mechanical ventilation presents
a challenge to even the most skilled clinician. Mushins
description of ventilators in his archetypal text (1) is
appreciated by many and addresses the classification
scheme that can be adopted to the less-sophisticated
mechanical ventilator. An innumerable count of authors
has used this classification method when writing about
mechanical ventilator support (24). Todays mechanical
ventilators are designed to provide life support using an
array of computerized logic systems, software utilities, and
even artificial intelligence models to deliver gas to patients.
This evolution of ventilators has led to a modernistic
classification system (5) to describe todays microprocessor-controlled mechanical ventilator. A classification system that is specific and well defined is intended to enhance
communications between clinicians (6). However, some
respected organizations (7) and clinicians (8) have been
reluctant to accept this new system for understanding
mechanical ventilation despite its acceptance by leading
members in the pulmonary and critical care medicine
community (911).
Basic Concepts
A mechanical ventilator is a system designed to alter,
transmit, and direct applied energy in a predetermined
manner to perform useful work (12). This work was generally accomplished with some pneumatic component
in earlier (first-generation) ventilators. Current systems
employ electronic circuitry that is microprocessor
controlled.
The energy we put into ventilators is in the form of
electricity or compressed gas. Mechanically speaking, a
506
ventilator will take the power input and convert or transmit that energy using the control scheme circuit to arrive at
a desired output. Put more plainly, that energy is transmitted or transfigured by the ventilator in a predetermined
manner to provide partial or full support to the patients
respiratory muscles.
Input Power
The input power or power source is the energy needed to
perform the work required to ventilate the patient.
Generally, two forms of input energy are used to operate
mechanical ventilators:
Electric
AC (alternating current)
DC (direct current)
Pneumatic. Many critical care ventilators in use
today incorporate electric and pneumatic power sources
to function properly because they employ advanced
mechanical systems in combination with microprocessor
control.
Electric
Critical care ventilators for use in the United States use
common electrical voltage (110115 V) to power them.
Some manufacturers have adapted their machines with
rechargeable batteries as an alternative in case of transport from one location to another or in case a power failure
erupts. Some disadvantages to the type of batteries (lead
acid) used is that they supply limited power, lasting
approximately 1 h and generally require a 1224 h recharging time.
Pneumatic
The availability of compressed gases of oxygen and air in
many hospital intensive care units (ICUs) makes it an
ideal energy source (energy pressure volume) to power
todays mechanical ventilator. Although the standard
regulated source gas pressure is 50 pounds per square
inch (psi), periodic fluctuations in gas pressure may occur
(13). Ordinarily, ventilators have internal regulators that
work at a lesser pressure (3045 psi) than the source
pressure. This will inherently maintain normal function
despite inconsistent source gas pressure. Aside from
unpredictable gas pressures, a pneumatically powered
ventilator is useful in environments using magnetic resonance imaging (MRI) or when the need for transport
arises. To date, only a few machines are capable of functioning on pneumatics only. Most ICU ventilators that are
pneumatically powered still require electricity to support
their control functions.
Power Conversion and Transmission
Power conversion and transmission refer to the mechanism(s) used to provide gas delivery. Sometimes this is
referred to as the drive mechanism. This is only partially
PL
FS1 FS2 PH a
A
where
PL Low or reduced pressure (generated pressure)
FS1 Force of the large spring (adjusting spring)
FS2 Force of the small spring (sealing spring)
PH High input pressure (source pressure)
a Area of the small seat
A Area of the large diaphragm
After gas is reduced from the PRV, it is delivered to the
patient by one of the following approaches:
1. Directly inflate the lung, as the Puritan-Bennett
7200.
2. Prime a spring weighted bellows as in the Servo
900C.
507
Control Scheme
Mechanical ventilators coordinate the delivery of gases
based on four variables: flow, volume, time, and pressure.
Therefore, the control variable becomes the variable that
the ventilator manipulates to create inspiration. A single
breath does not reflect significant changes in compliances
and resistance. However, flow, volume, time, and pressure
can shift and are regulated by the ventilator. In general, if
flow, volume, time, or pressure are individually preprogrammed, the others must respond. The control variable
will remain constant in the presence of changes in impedance (resistance and compliance). For example, a ventilator is a volume controller if the volume is measured and
used to control the volume signal. Many of todays volume
ventilators are truly flow controllers. They derive a volume
measurement from a flow signal. The signal is measured
and calculated and displayed as a volume unit of measure
on the ventilator display window.
Now that we have discussed what is controlled, let us
examine how it is controlled. In the openloop system, the
user selects the variable (volume, pressure, and flow), for
input and observes the output variable (volume, pressure,
and flow), which mirrors the actual valve. The operator
handles any needed adjustments. The closedloop system
analyzes the data using a feedback signal and automatically modifies the input in an attempt to match the reference value.
Phase Variables. Control of the breath requires the
ventilator to perform four phases during a breathing cycle
(22):
1.
2.
3.
4.
508
the trigger phase of the ventilator. With patient triggering, the ventilator senses the patient effort to initiate gas
delivery. The breath is flow, volume, or pressure triggered
if the patient initiates the breath. Most modern adult
ventilators have a frequency, breathing rate, or respiratory
rate control knob that serves as the time trigger. Manual
trigger is available on most ventilator control panels as
well.
Limit Variable. A limit variable is a parameter that can
reach a preset level before inspiration ends, but it does not
terminate the inspiration phase (23). This is often confused
with a cycle variable. A limit variable does not terminate
inspiration; it sets the upper boundaries for pressure,
volume, or flow. An example present in many critical care
ventilators is the ability for an operator to perform an
inflation hold of plateau maneuver. The ventilator is
allowed to deliver a preset volume, but inspiration does
not end until a preset time interval has elapsed. The
volume is limited (held and maintained) until the preset
pause time is reached.
Cycle. Inspiration will end when either time, pressure,
flow, or volume reaches its preselected value. Unlike the
limit variable, the inspiration phase will end (cycle off).
Baseline Variable. The variable controlled during the
expiratory phase is the baseline variable (24). Although
flow or volume can serve as the baseline variable, pressure
is the most commonly used. Expiratory pressure can be set
to atmosphericZero. This is called ZEEP (zero end
expiratory pressure). ZEEP is obtained when the ventilators exhalation valve opens to the atmosphere, exposes the
patients airway to the atmosphere, and exposes the
patients airway to a relative pressure of zero. Pressures
exceeding atmospheric are referred to as PEEP (positive
end expiratory pressure) or CPAP (continuous positive
airway pressure). Two well-documented phenomena
applicable to PEEP/CPAP therapy are reduced functional
residual capacity (FRC) and extravascular lung water
(2527).
Conditional Variables. Specific patterns of breath delivery are examined by the microprocessors control logic
system. The ventilator may be set to keep the breath
constant or perform more complex maneuvers. The ventilator algorithm for a particular set of breath delivery
patterns makes this determination.
Modes of Ventilation. A mode of ventilation represents
a combination of control, phase, and conditional variables
that establish a set pattern of mandatory and/or spontaneous breaths (28).
Output. Most ventilator waveforms can be classified as
one of the following:
1.
2.
3.
4.
Exponential
Ramp
Rectangular
Sinusoidal
VENTILATOR OPERATION
Introduction
The scope of medical practice expanding to accommodate
the needs of those with respiratory diseases is immense.
The field of respiratory therapy alone encompasses over
35,000 persons in the United States (33). As one may glean
from the previous section of this article, not unlike other
areas of medicine, when the need for new technology and
therapeutic interventions is required, along with it will
come a vast array of specialists, technical support, ancillary staff, and commercial entrepreneurs. The use of ventilators is expensive and represents approximately 10%
incidence and contributes significantly to hospital costs
(34). Although these costs are impressive, so are the diseases from which the patients suffer, and the true cost is
patient mortality, which is invariably high (35). To that
end, we have experienced increased understanding of the
pathophysiology of their diseases as well as have enjoyed a
significant increase in the technologic advances to support
them.
The initial aim of ventilatory support has been justified
to aid those persons suffering from neuromuscular disorders such as poliomyelitis or tetanus. The practice of
medicine precludes one from solely defining a disease
and indicating an intervention. But, rather, it identifies
a derangement from normal and determines whether it
causes harm. Should this be the case, then one should
implement a therapeutic change. In the case of mechanical
ventilatory support, we refer to the concept of work of
breathing (WOB) (36).
Work Force Distance
Force Pressure Area
Distance Volume=Area
Work Pressure areaVolume=Area
Work Pressure Volume
WOB Tidal Volume Transpulmonary Pressure
The tidal volume that is normally generated results
from a relatively small pressure gradient from the intrapleural space to the atmosphere drawing gas inward.
Exhalation is then passive when the pressure gradient
is reversed, and the pressure then exceeds atmospheric.
The relationship between pressure and volume is known
as compliance. Pulmonary parenchymal (Cp) compliance
is one component of total lung compliance (CT) that would
509
Comments
ABG diagnosis
Physical diagnosis
Cardiac arrest
Neurosurgery
Lung protective strategy
510
Work of
Breathing
Eucapnia and
Normal pH
Significant
Not required
Not required
Yes
Yes
No
Volume TV
Pressure TV
Trigger
Limit
Cycle
Tidal volume
Peak pressure
Modes
Patient or time
Flow
Volume
Constant
Variable
Assist/control (synchronized) intermittent
Mandatory ventilation
Patient or time
Pressure
Time or flow
Variable
Constant
Assist/control (synchronized) intermittent
Mandatory ventilation
Pressure support
1 second
inflation
hold
10
40
100
B
20
50
3
0
3
3
0
3
10
3
0
3
Figure 1. Airway pressure tracings of the four standard volumepreset modes. Thick solid lines represent ventilator breaths; thick
dotted lines represent spontaneous breaths; and thin dotted lines
refer to what the spontaneous pattern would have been without
the ventilator breaths. IMV, intermittent mandatory ventilation;
SIMV, synchronized IMV. Reprinted with Permission from
Reference (36).
1.5
Seconds
10
IMV mode
Flow l/min.
0
3
Pressure cmH2O
Control mode
10
SIMV mode
511
Figure 2. Schematic illustration of inspiratory cycle for volumepreset (1000 mL) tidal volume delivered by square-wave generator
in 1 s, followed by 1-s inflation-hold maneuver. Note that the
inspiratory cycle is 2 s, although tidal volume is delivered by
the ventilator in 1 s. Normal compliance and resistance are
assumed. Proximal airway pressure is shown as a solid line,
alveolar pressure as a dashed line, and gas flow in airways as a
dotted line. Peak airway pressure (A) is achieved near the end of
tidal volume delivery, at which point there is considerable gradient
between peak airway pressure and alveolar pressure that results
in continued flow to the lung. Airway pressure rapidly diminishes
as flow continues toward alveoli. Note that measurable flow in the
system has essentially ceased 0.5 s after the ventilator has delivered tidal volume (B); however, a gradient remains between
airway and alveolar pressures. An elevated peakpressure (A) in
the presence of normal plateau pressures indicates increased
airway resistance, which may include bronchospasm. To attain
true plateau pressure, in which the airway pressure reflects the
average peak alveolar pressure, an additional 0.5 s of inflation hold
is required after the absence of measurable flow in the system.
Reprinted with permission from Reference 42.
512
1600
1400
Volume mL
1200
1000
800
600
400
200
LIP
EELVZEEP
0
10
20
30
Pressure cmH2O
40
50
.7
.6
.5
Kf,c (o)
ml
mincmH2O100g
.4
.3
.2
r=0.72
.1
0
10
20
30
40
50
60
70
513
514
VENTILATORY MONITORING
RESUSCITATION;
CONTINUOUS
POSITIVE
VENTILATORY MONITORING
STEVEN R. KNOPER
STUART F. QUAN
University of Arizona College of
Medicine
INTRODUCTION
One of the most important aspects of the clinical care of
patients with known or suspected cardiopulmonary disease is monitoring the adequacy or status of their ventilatory function. However, in order to understand why
various parameters of lung function are monitored, a
few aspects of basic respiratory physiology require review.
Although the lungs perform important metabolic and
endocrine functions, their primary function is gas
exchange. They provide the vehicle by which oxygen
(O2) in inspired air moves into venous blood and carbon
dioxide (CO2) in venous blood is released into expired gas.
The mechanisms by which these processes occur are complex, but can be subdivided into four phases. The first
phase involves the movement of gas into and out of the
lungs themselves. This aspect of respiratory physiology is
termed lung mechanics. During spontaneous breathing,
contraction of the diaphragm and intercostal muscles
increases negative pressure within the intrapleural space,
leading to lung expansion. This results in a pressure
gradient along the airways causing gas to flow into the
lungs and to eventually reach the alveoli. With relaxation
of the inspiratory muscles, the elastic recoil of the lungs
reverses the pressure gradient resulting in gas being
expired through the mouth into the atmosphere. In the
second phase, gas exchange occurs in the alveoli. By the
process of diffusion across the alveolar capillary membrane, O2 enters and CO2 exits the vascular system.
The third phase involves the transport of O2 and CO2 in
the blood, and is intimately related to adequate cardiovascular and hematologic functioning. Oxygen is carried
in the blood primarily in a complex with hemoglobin in the
red blood cells. A small amount of O2 is also dissolved in
plasma. The total amount of O2 delivered throughout the
body is a function of the volume of O2 in the blood, and the
rate of delivery or cardiac output. Transport of CO2 in the
body is more complex, but also is related to the properties
Ventilatory monitoring usually is performed for four general clinical indications: (1) diagnostic, (2) therapeutic, (3)
prophylactic, and (4) safety considerations. With respect
to diagnostic use, the goal of monitoring is to obtain
information pertinent to making a specific etiologic diagnosis of a disease entity or process. For example, in
myasthenia gravis patients who are having an acute
deterioration in ventilatory function, vital capacity (VC)
measurements (the maximum volume excursion of which
the lungs are capable by voluntary effort) are obtained after
injection of a short-acting cholinesterase inhibitor (edrophonium, Tensilon). Documentation of an increase in VC suggests the need for an increase in anticholinesterase
medication, whereas a deterioration is evidence for excessive
effect from medication. Another frequently encountered
situation where ventilatory monitoring is used diagnostically
is the continuous monitoring of airflow and ventilatory effort
in sleep disorders laboratories to detect evidence of sleep
disordered breathing (2).
A number of ventilatory parameters are useful in monitoring the therapeutic effect of specific treatment modalities. The most frequently encountered situation is where
arterial O2 and CO2 gas tensions are sampled following
institution of supplemental O2 or mechanical ventilation.
Measurement of respiratory system compliance following
application of positive end-expiratory pressure (PEEP) in
mechanically ventilated patients with acute respiratory
failure is another example of where ventilatory monitoring
is used to determine the effects of a treatment modality (3).
In both the aforementioned examples, therapy frequently
is adjusted using results obtained from the ventilatory
parameters monitored.
Ventilatory monitoring commonly is performed prophylactically with the goal of detecting a perturbation in
normal or baseline respiratory function so that treatment
can be instituted early. For example, apnea monitors are
employed in infants suspected to be at risk for sudden
infant death syndrome. In this clinical situation, alarms
are activated if life-threatening apnea or bradycardia
occurs so that the infant can be resuscitated before a full
cardiorespiratory arrest ensues.
Finally, safety considerations require ventilatory monitoring when certain categories of biomedical life support
devices are used. In patients with pulmonary disease, a
VENTILATORY MONITORING
Table 1. Levels of Ventilatory Monitoring
Visual observation
Intermittent objective measurements
Continuous or automated measurements
Computerized analysis with treatment algorithms
515
Patients who are critically ill may require the third level
of monitoring intensity, which is continuous measurement
of various ventilatory parameters over time. In most intensive care units, devices are available to continuously track
breathing frequency. Patients receiving mechanical ventilation have continuous monitoring of their airway pressures and exhaled tidal volumes for safety considerations.
Recent technological advances now allow for continuous
monitoring of arterial and venous oxygen saturations. In
the most sophisticated intensive care units, on-line monitoring of exhaled gases from ventilated patients and complex measurements of lung mechanics, such as resistance
and compliance, can be performed.
Finally, the highest level of monitoring is the use of
computer algorithms to not only monitor various ventilatory parameters, but to also adjust therapy according to the
values obtained without human intervention. The technology required for such monitoring is undergoing continuous
development, and there is increasing use in patient care
applications. This is particularly evident on newer microprocessor ventilators where some ventilator modes allow
for automatic adjustments to the level of ventilator support
according changes in patient lung mechanics.
PARAMETERS USED IN MONITORING LUNG MECHANICS
Breathing Frequency
The most common measurement of ventilatory function is
an assessment of the patients breathing frequency.
Usually, this is performed by visually counting the breathing frequency over a 3060 s period of time, although
biomedical devices also can be used for this purpose. Normal individuals breathe at a frequency of 12 min. However, this rate is markedly altered in patients with lung
disease. Reductions in spontaneous respiratory rate are
diagnostic of ventilatory dysfunction and suggest central
depression of ventilatory control centers in the brain stem.
Examples of clinical situations in which this might occur
are narcotic overdose, incomplete recovery from a general
anesthetic, and primary central alveolar hypoventilation.
Whereas reductions in breathing frequency indicate ventilatory dysfunction, an increase in spontaneous breathing
frequency (tachypnea) is more nonspecific since individuals can voluntarily increase their breathing frequency
in response to physical or psychological stress, or an
increase in metabolic demands. However, if a nonpulmonary basis for an increase in breathing frequency can be
excluded, tachypnea generally indicates the presence of
lung disease. Common examples are pneumonia, congestive heart failure with pulmonary edema, and asthma.
Lung Volume and Airflow. An assessment of the volume
of air inspired and expired with each breath (tidal volume,
VT) is an important ventilatory parameter since adequacy of
ventilation is determined not only by the breathing frequency, but also by the VT. The spontaneous VT in normal
individuals varies according to their size, but in an average
adult is 500 mL. Ventilatory dysfunction, whether from
processes such as parenchymal pulmonary disease or a
reduction in central respiratory drive, generally results in a
516
VENTILATORY MONITORING
VENTILATORY MONITORING
Cst CL Ct
where Ct is the compliance of the thorax.
Dynamic lung compliance (Cdyn) is the change in lung
volume occurring with a change in pleural pressure
between two points of instantaneous zero flow during
breathing (9).
In the respiratory system, changes in compliance are a
function of two factors: the elasticity of the tissues and lung
volumes. In the upright position, the normal value for Cst in
adults is 100 mL/cm H2O, and the normal value for CL is
2.0 L/kPa. However, many types of lung pathology such as
pulmonary edema and pneumonia result in a reduction of
both Cst and CL. In addition, normal values decline with
decreasing lung volume. Thus, the normal Cst of a small
animal or infant is less than an adult human. Dynamic
lung compliance and CL are virtually identical in the
absence of significant parenchymal lung disease. However,
with airways disease, all alveoli do not ventilate evenly
during dynamic conditions, with some gas exchanging
areas ventilating slower than others. This phenomenon
also has been described as time constant disparity. Because
of this disparity in time constants, these slow ventilating
areas do not participate fully in gas exchange, and in effect
a smaller lung volume is ventilated with each breath. In
517
contrast, during static conditions, a disparity in time constants does not influence the distribution of ventilation.
Therefore, Cdyn is <CL in the presence of significant airways disease. Another measure of lung elasticity called the
dynamic characteristic (Cdch) (10) also has been
described. It is calculated in patients receiving mechanical
ventilation as VT divided by the difference between Pmax
and PEEP. However, Cdch is not just a reflection of lung
compliance, but also is influenced by changes in airways
resistance.
Measurements of both Cdyn and CL require an estimate
of intrapleural pressure that, in most cases, is obtained
using an esophageal balloon. Because accurate esophageal
pressures are difficult to obtain, especially in critically ill
patients, clinical measurement of these ventilatory parameters are uncommon. However, Cst only requires measurement of VT and airway pressure, and thus is easily
obtained in most patients receiving mechanical ventilation. Since, in most patients, changes in Cst are primarily a
result of changes in CL, serial measurements of Cst frequently are used to follow changes in lung elasticity. For
example, maximizing Cst during application of PEEP has
been shown to correspond to the best levels of oxygen
transport (product of the cardiac output and the arterial
oxygen content) (3). Serial measurements of both Cst and
Cdch are useful in many patients with acute respiratory
failure who are receiving mechanical ventilation. A change
in both these parameters usually signifies an alteration in
the properties of the lung parenchyma such as increasing
pulmonary edema or pneumonia. However, a change in
Cdch without a change in Cst is indicative of an increase in
airways resistance such as might occur with the onset of
bronchospasm or mucous plugging of the airways (10).
Measurements of compliance and resistance summarize
pressurevolume relationships in the lung. These can be
depicted graphically with two-dimensional (2D) plots of
volume versus pressure. A decrease in compliance will
be represented by a decrease in slope of this relationship,
whereas bowing of the volumepressure relationship is
observed when airways resistance is increased. Analysis
of the inspiratory volumepressure curve may aid in determining the optimum level of PEEP for patients with the
acute respiratory distress syndrome who require mechanical ventilation. The optimum level of PEEP is suggested by
the inspiratory airway pressure at which the slope of the
volumepressure curve appears to increase (11). In some
intensive care units, on-line plots of volume versus pressure can be obtained, but their value in the care of patients
has not been proved.
Work of Breathing. In physics, linear work is defined as
the product of force times distance. The analogous situation when applied to the movement of air into the lungs is
described by the product of pressure times volume. Therefore, the work of breathing is equivalent to the cumulative
product of the transpulmonary pressure and the volume of
air moved at each instant in time (12). Work of breathing
measurements have been proposed as a method of determining whether mechanically ventilated patients are able
to breathe spontaneously (13). Unfortunately, accurate
determinations require simultaneous measurements of
VENTILATORY MONITORING
pleural pressure (usually estimated from esophageal pressure), and airflow. Therefore, work of breathing measurements have not found great utility in the clinical
management of patients.
Other Parameters. The rapid shallow breathing index
(RSBI) is frequently used to assess the ability of a patient to
breath without ventilator support (14). It is calculated by
measuring the breathing frequency and dividing it by the
VT in liters. High values (>105) indicative of low VT and a
high breathing frequency suggest that a patient cannot be
removed from the mechanical ventilator. However, there
has been some controversy concerning the predictive value
of this parameter in all clinical situations.
Ventilatory drive is another parameter that can be
monitored. Although measurement of the minute ventilation in response to hypoxia or hypercapnia are indexes of
central drive in the absence of impairment of neuromuscular or mechanical pulmonary disease, measurement of
the airway pressure generated within the first 100 ms
after airway occlusion (p0.1) is generally recognized
as the best indicator of the central drive (15). Unfortunately, this is difficult to accomplish without specialized
equipment.
PARAMETERS USED IN THE ASSESSMENT OF GAS
EXCHANGE
100
90
Per Cent Saturation of Hemoglobin
518
80
70
60
50
40
30
20
10
0
P
O2 10 20
30
40
50
60
70
80
90
100
mmHg
Figure 1. Oxyhemoglobin dissociation curve. The graph shows
the relationship between hemoglobin saturation and oxygen
tension. Above 60 mmHg, the curve becomes progressively
flatter so that little additional saturation occurs when the PO2
is <6070 mmHg.
Oxygenation
The amount of oxygen contained in arterial blood (oxygen
content, CaO2) is determined by the arterial oxygen tension (PaO2), the percent saturation of hemoglobin (Hgb)
with oxygen (SaO2), and the Hgb concentration in arterial
blood:
CaO2 1:34 Hgb SaO2 0:003 PaO2
where CaO2 mL O2/100 mL blood, 1.34 mL O2/g Hgb,
Hgb g/100 mL blood, SaO2 % saturation, 0.003 mL O2
dissolved in blood/mmHg, PaO2 mmHg.
In most circumstances, adequacy of oxygenation is
monitored by measurement of the PaO2 or the SaO2.
Although the PaO2 and SaO2 are intimately related to
each other, their relationship is not linear (Fig. 1), but
rather is described by a sigmoid curve. At levels of
oxygen tension greater than 60 mmHg, there is little
increase in SaO2 with increasing values of PaO2. In contrast, when the PaO2 falls <60 mmHg, SaO2 declines
rapidly with decreases in PaO2. Therefore, monitoring
of SaO2 as an estimate of PaO2 is of little value when
the PaO2 is >7080 mmHg, since significant alterations in
PaO2 will not be reflected by corresponding changes in
SaO2. At sea level, the normal PaO2 is 100 mmHg and the
SaO2 is 97%. However, normal values may vary according
to alterations in barometric pressure and increasing age
(16). Occasionally, arterial oxygen content (normal
value 9.5 mL O2/100 mL blood) is monitored as an indicator of oxygenation. Because most of the oxygen in blood
is carried in combination with Hgb, this may be of value
when Hgb levels are severely abnormal or fluctuating
rapidly.
VENTILATORY MONITORING
519
Fully
oxygenated
blood (CcO2)
Mixed
venous
blood
(CvO2)
QT =
CaO2
CcO
2
CvO2
CcO
2
Arterial
blood
(CaO2)
(b)
(a)
Ventilation
Fully
oxygenated
blood
Mixed
venous
blood
Shunted blood
(CcO2)
(CvO2)
=15 vols %
=15 vols %
Ventilation
2)
(CcO
=20 vols %
Arterial
blood
(CaO2)
=17.5 vols %
Fully
oxygenated
blood
Mixed
venous
blood
(CvO2)
=10 vols %
Shunted blood
(CcO2)
=10 vols %
2)
(CcO
=20 vols %
Arterial
blood
(CaO2)
=15 vols %
520
VENTILATORY MONITORING
VENTILATORY MONITORING
index of respiratory effort in some sleep disorders laboratories. Otherwise, however, they are not frequently used
clinically for continuous monitoring. Direct measurement
of pleural pressure using a small catheter placed into the
pleural space has also been reported (21), but is not commonly performed.
Respiratory effort also can be monitored using strain
gauges (2) and magnetometers (22) placed around the chest
and abdomen. Magnetometers measure the change in
magnetic fields, produced by electrical coils placed on
opposite sides of the body. If expansion of the lungs can
be considered as a volume change with only 28 of freedom,
the rib cage being 18 of freedom, and the abdomen the
other, then lung volume changes are nearly linearly
related to changes in the anteroposterior diameters of
the chest wall and abdomen. Although the accuracy of
magnetometers is limited for the same reasons mentioned
for impedance devices, their reliability may be increased if
additional magnetometers are used to measure lateral
chest wall movement. However, for clinical purposes, both
strain gauges and magnetometers are not usually used for
quantification of tidal volume. Rather, these methods are
used primarily in sleep disorders laboratories for a qualitative estimate of respiratory effort.
Intercostal EMG measurements can be obtained by
placement of surface electrodes in the intercostal spaces
in the anterior axillary line, and can be employed as an
indicator of respiratory effort (2). However, when used in
diagnostic studies for sleep disordered breathing, intercostal EMG activity may not be representative of respiratory
effort during rapid eye movement sleep because of the
inhibition of skeletal muscle tone during this stage of sleep.
Frequency analysis of the intercostals and diaphragm
EMG has been used by some investigators to study fatigue
of the respiratory muscles (23). Although EMG evidence of
respiratory muscle fatigue can be detected before clinical
findings of acute respiratory failure, routine application of
processed respiratory muscle EMG data to patient care has
not occurred.
A more reliable method of quantifying breathing frequency and airflow is inductance pneumography. Similar
to magnetometers, this technique considers lung volume to
be a result of alterations in two compartments: the rib cage
and the abdomen. Therefore, the volume of each tidal
breath is theoretically attributable to the independent
movement of both these compartments. Hence, an inspired
volume will be equal to the sum of the volume changes from
both compartments. To measure the volume changes in
each compartment, bands of insulated wire coils are placed
around the chest and abdomen and held in place with a
mesh vest. With appropriate calibration, changes in inductance of the coils are accurate reflections of both alterations
in lung volume, and the relative contributions of the chest
and abdomen to the volume changes (24). Clinical usage of
inductance pneumography has been limited primarily to
ventilatory monitoring for polysomnography.
There are several categories of devices available that
primarily measure airflow (Table 2). With many of these
devices, flow rate can be integrated over time to derive a
measurement of Vt or VC. Thermistor flow meters are
commonly used in sleep disorders laboratories, and in
521
522
VENTILATORY MONITORING
VENTILATORY MONITORING
523
524
VENTILATORY MONITORING
production of a plethysmographic waveform. The amplitude of the waveform is a function of the wavelengths of
light used, the hemoglobin saturation, and the size of the
pulse changes. Since the wavelengths of light used are
known, beat-to-beat arterial oxygen saturation can be
calculated using the magnitude of the pulse changes and
a mathematical model based on the BeerLambert law.
Current pulse oximeters are quite compact, and can be
used for ambulatory and home monitoring. In comparison
to ear oximeters, they also provide continuous monitoring
of the arterial pulse rate. Their use in clinical medicine has
proliferated exponentially. The major disadvantage to both
ear and pulse oximeters is the inability to measure arterial
saturation in low cardiac output states when tissue perfusion is impaired.
The oxygen content of blood can be calculated from the
hemoglobin concentration, the saturation of hemoglobin
with oxygen, and the pO2 in the blood sample, as previously
described for the arterial oxygen content. In most situations, calculated oxygen contents are used when determination of oxygen contents is required. However, devices
and approaches have been developed to directly measure
oxygen content. In one approach that is used commercially,
the hemoglobin is lysed to release all of the oxygen in the
sample into solution. The amount of oxygen is then analyzed using one of a variety of techniques (see below) More
cumbersome and difficult is to measure oxygen content by
carbon monoxide displacement, or by volume extraction
and manometric measurement. The first technique
involves displacement of oxygen in the sample to be analyzed by addition of carbon monoxide, and subsequently
measuring the increase in pO2 in the resultant mixture
(38). The second technique, described by Van Slyke and
Neill (39), involves extraction of the gas from solution with
various reagents over mercury, creating a Torricellian
vacuum, and measuring pressure changes with a manometer. Both of these techniques are seldomly used today
and are primarily of historical interest.
Measurement of Oxygen in Gas
Several techniques are available to measure the concentration of oxygen in gas:
Paramagnetic analyzers
Electrical analyzers
Galvanic fuel cell
Polarographic gas analyzers
Ionized oxygen electrode
Scholander volumetric technique
Gas chromatography
Mass spectrometry
Paramagnetic analyzers use the principle that oxygen
alters a magnetic field when introduced into it (40). With
one such device, oxygen introduced into the magnetic field
causes a glass dumbbell, filled with nitrogen and suspended in the field, to rotate. The amount of rotation of
the dumbbell is proportional to the percentage of oxygen
concentration. Since the alteration in the magnetic field is
VENTILATORY MONITORING
Container
525
Voltmeter
O2
Gas-permeable
membrane
Hg/Hg2Cl2
O
O2
From
cathode
From
anode
Ag/AgCl
anode
Electrolyte
solution
Pt cathode
generated between the two platinum surfaces that is proportional to the oxygen concentration outside the tube (4).
The most cumbersome method of measuring oxygen
concentration in a gas is the Scholander volumetric technique (41). With this technique, volume changes in the
sample gas are measured as the various gaseous components are absorbed from the sample. This method is of little
clinical utility for continuous monitoring of oxygen concentrations, but is an important reference technique against
which more portable units can be compared.
Another, uncommonly used, gas analytical technique in
clinical medicine is gas chromatography. With this method,
the gas sample to be analyzed is added to the flow of a
carrier gas. The carrier gas (usually helium) transports the
sample through a column that contains material having a
differential affinity for the components of the sample. The
column impedes the passage of components with higher
affinities, and therefore separation of the components
occurs. After passage through the column, the components
of the gas sample can be measured using a nonspecific
sensor. Usually, this is done by detecting changes in thermal conductivity induced by the components of the gas
sample, but other types of sensors also can be employed
(42). Gas chromatography is an accurate method for analyzing O2, CO2, and anesthetic gas concentrations. However, the slow response time (minutes) is a major
drawback. Nevertheless, it has been used for in vivo measurements of arterial pO2 (see the section Measurement of
Oxygen in Blood).
The most expensive, but also most versatile technique to
analyze oxygen and other gases is mass spectrometry (MS)
(4,26). With MS, the sample gas is passed through an
electron gun that ionizes the gas particles. The ionized
gas particles are then drawn into a magnetic field, where
the particles are deflected toward a collection plate. The
larger the mass of the gas particle, the farther it will travel
down the collection plate. The collection plates count the
number of particles of each molecular mass impacting on
the plate over time. From this information, the relative
composition of the sample gas can be computed. Mass
spectrometers are quite accurate, but very expensive. However, one unit can be used to sample gas from multiple
sources in a similar way to the method a mainframe
computer uses to perform multiple tasks. Such arrangements are used in some operating rooms and intensive care
units.
Chloride
ion
solution
~ 6.8
pH =
Ag/AgCl
wire
KCl solution
Liquid
Blood
KCl
sample connection
Measurement
(Ag/AgCl)
electrode
Reference
(calomel)
electrode
526
VENTILATORY MONITORING
VENTILATORY MONITORING
527
BIBLIOGRAPHY
Evolving Technology in Ventilatory Monitoring. In vivo
continuous measurement of O2, CO2, pH, and other substances in the future may be clinically useful using optode
technology (46,47). An optode is a fiberoptic light bundle
coupled to a microcuvette where a chemical reaction can
occur. For example, the substance to be analyzed diffuses
through a semipermeable membrane into the cuvette
whereupon a chemical reaction would be initiated. The
chemical reaction would produce a change in the optical
properties of the reagent in the cuvette that would be
detected by light directed along the fiberoptic light bundle.
Wavelength specific absorbance can be used to quantify
paCO2 and pH, and fluorescence is useful for paO2, as well
as paCO2 and pH. Imprecision of the paO2 sensor has led to
a hybrid probe, with a miniaturized Clark pO2 electrode
combined with absorbance paCO2 and pH sensors, as well
as a thermocouple for temperature measurement (43).
Clinical challenges for continuous on line measurement,
utilizing an in vivo placement, primarily deal with inaccuracies of paO2 measurement secondary to arterial wall
contamination or limited blood flow because of thrombus
formation and vasospasm. In addition, probe longevity and
cost, as well as pulse pressure dampening over time, have
been issues. Because of these problems, an on demand ex
vivo placement in the arterial line has been tested and has
sufficient accuracy, but does not have the advantage of
continuous measurement (48).
The ion selective electrode (ISE) or the field effect
transistor-based chemical sensor (ISFET) are other new
methods of continuously monitoring pH and pCO2 that
may become feasible in the future (47,49). With both these
devices, the ion to be analyzed is isolated from the blood
using an ion selective membrane. An ISE consists of an
electrode surrounded by a buffer solution that is separated
from a biological fluid or tissue by an ion-selective membrane. The electrical potential at the measurement electrode is compared to that of a reference electrode, and the
potential difference is proportional to the concentration of
the ion being measured. The ISFET is an insulated gate
field-effect transistor without a metal electrode at the
gate. Measurement of the concentration of a specific ion
is a function of modulation of current flow within the
semiconductor induced by the ion in the surrounding
biological tissue or fluid. However, similar to optodes, both
the ISE and the ISFET are still in the early developmental
stages. Current problems include long-term stability,
ambient light and temperature sensitivity, and interference from extraneous ions. With both the ISE and ISFET,
control thrombus formation on the probe remains a problem. In addition, an adequate O2 sensor has not been
developed.
528
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
INTRODUCTION
The visual field is the total area where objects can be seen
in the peripheral vision while the eye is focused on a central
point. Visual field testing is a critical part of the eye
examination and is mandatory for the detailed evaluation
of unexplained visual loss. Of the various reasons for
conducting a visual field examination, the most common
disorder is glaucoma. In glaucoma, field testing is essential
not only to establish the diagnosis, but also to follow-up and
determine the effectiveness of treatment. There are various modalities available for visual field testing customized
to particular eye disorders. This article provides a concise
review of the various methods of visual field testing and
there applications for clinical and research purposes.
METHODS OF VISUAL FIELDS TESTING
There are various ways of testing the visual field (1). It can
be done in a simple manner in the clinic or may involve
sophisticated equipments. The commonly used modalities
are described below.
1. Confrontation visual field exam: It is a quick
evaluation of the visual field done by a physician
sitting directly in front of you. With one eye covered,
529
Blind spot
Retinal
sensitivity
in decibels
0 dB
530
VISUAL PROSTHESES
FUTURE DIRECTIONS
There have been considerable developments in visual field
testing in the past decade, and it has opened up areas for
the development of new testing and analysis programs. A
VISUAL PROSTHESES
JEAN DELBEKE
CLAUDE VERAART
Catholic University of Louvain
Brussels, Belgium
INTRODUCTION
Minute electrical stimuli delivered to the retina, the optic
nerve, or the occipital cortex can induce light perceptions
called phosphenes. The visual prosthesis aims at exploiting
these phosphenes to restore a form of vision in some cases
of blindness. Very schematically, a camera or a picture
capturing device transforms images into electrical signals
that are then adapted and passed on to some still functional
part of the visual pathways, thus bridging the defective
structures. The system has at least some parts implanted,
including electrodes and their stimulator circuits. A photosensitive array in the eye could provide the necessary
image input, but most approaches use an external miniature camera. Typically, the visual data handling requires
an external processor and the power supply as well as the
data are provided to the implant by a transcutaneous
transmission system.
Despite a first pioneering attempt by Brindley and
Lewin as early as 1968 (1) only very few experimental
visual prostheses have been implanted in humans so far.
The limited accessibility of the involved anatomical structures, the poorly understood neural encoding, and the huge
amount of information handled by the visual nervous
system have clearly hampered a development that can
not yet be compared with the far more advanced evolution
of cochlear implants (see article on Cochlear Implants in
this encyclopedia). The visual prosthesis is still at a very
VISUAL PROSTHESES
(b)
(c)
Visual field
Sclera
coroid
epithelium
Eyes
Rod
Receptor
cells
Retina
Cone
Optic chiasma
Optic nerve
Bipolar cells
Lateral
geniculate
nuclei
Retinal
ganglion cells
Towards
higher
visual
structures
Optic radiations
Light
531
Visual cortex
Figure 1. (a) Schematic representation of the visual pathways from the eye to the visual cortex
with an indication of the hemifield segregation at the level of the chiasma. (b) Retinotopy mapping
all along the visual pathways. Note also the cortical amplification, that is, disproportional cortical
representation of the central visual field. (c) Enlarged view of a cut through the retina showing the
various layers and their position in relation to light entering the eye.
532
VISUAL PROSTHESES
VISUAL PROSTHESES
533
Implanted
antenna
External
processing
Artificial
retina
or video
camera
Antenna
driver
From monitoring
equipment
Neurostimulator
External
antenna
Neural
interface
Implanted components
Figure 2. General layout of a visual prosthesis, with the external components on the left and the
implanted components (shaded) on the right.
534
VISUAL PROSTHESES
VISUAL PROSTHESES
535
536
VISUAL PROSTHESES
External
processing
unit
Digital
memory
Image
acquisition
and
processing
Rechargeable
battery pack
Driver
interface
and
modulation
Artificial
retina
or video
camera
Antenna
driver
Communication
interface
Monitoring
equipment
Voltage
regulator
+
E
T
O
DAC
470 nF
Logic &
memory
Measure
ADC
-E
Neurostimulator unit
Figure 5. Detailed representation of the implanted components of Figs. 2 and 3.
E
L
E
C
T
R
O
D
E
A
R
R
A
Y
VISUAL PROSTHESES
Table 1. Example: Main Specifications of the Optic Nerve
Prosthesis
Image processing
Pixel size
Processed visual field
Telemetry
Forward carrier frequency
Forward data rate (Frequency
Shift Keying modulation)
Data frames length (including 6 bit CRC)
Return carrier frequency
Return data rate
Maximal power transmission (class E)
Maximal antennae separation distance
Implant
Power consumption
No. of independent current sources
Current sources
Time resolution
Output voltage range
Maximum output current
Current resolution (exponential)
Electrodes
Number of contacts
Contact recess depth
Contact area (platinum)
1 18
32 648
12 MHz
3 Mbit s1
64 bit
24 MHz
1.5 Mbit s1
120 mW
5.5 mm
80 mW
8
21 ms
9 to 9 V
3.2 mA
8 bit sign
8
80 mm
0.2 mm2
537
538
VISUAL PROSTHESES
Figure 6. Picture of a number of different electrodes characterising the various approaches to the
visual prosthesis. (a) Details of a MicroPhotoDiode (MPD) chip intended to be implanted subretinally
in the space normally filled up by cones and rods. (Courtesy of Eberhart Zrenner.) (b) The Utah
Cortical Electrode Array. (Courtesy of Richard A. Normann.) (c) An overview of the epiretinal
prosthesis with wireless radio frequency transmission being built by researchers at the Boston
VA hospital, Harvard Medical School and Massachusetts Institute of Technology. Only a small
square end on the left will enter the eye. (Courtesy of Joseph Rizzo.) (d) The optic nerve spiral cuff
electrode.
VISUAL PROSTHESES
539
0.4 mA
1.6 mA
a
42 ms
Cathodic Current
2.4 kV
2.3 kV
342 ms
5.0 kV
3.2 kV
540
VISUAL PROSTHESES
VISUAL PROSTHESES
541
542
VISUAL PROSTHESES
figure orientation, object localization, object discrimination, and grasping) as well as mobility trials (obstacle
localization and avoidance, landmark localization, and
identification). Evaluation of the usefulness of the visual
prosthesis in a natural environment will be essential.
Further down the road to improvement, face recognition,
scene identification, and finally reading tests will perhaps
also be considered but much better resolutions are still
required (29).
HUMAN AND MEDICAL ASPECTS
Candidates for a Visual Prosthesis
No matter what approach is chosen, all visual prosthesis
system require a functional visual brain to ultimately
interpret their output. This means that, with todays limited performances, only people losing sight after the critical
period of development can be considered as suitable candidates.
Another selection criterion is the severity of blindness.
As long as the performances of the systems are questionable, only totally blind persons should be considered as
candidates. The risk of interfering with residual vision can
indeed only be taken if the expected results are significantly better than the remaining visual abilities. In addition, the evaluation of the rather limited performances of
an implant could be obscured by any surviving visual
functionality.
Other selection criteria are dependent on the chosen
approach. All the prechiasmatic approaches (subretinal,
epiretinal, optic nerve) require the survival of retinal ganglion cells and their axons in the optic nerve. Terminal
retinitis pigmentosa emerges as the condition most typically fulfilling all the selection criteria. Except in cases of
brain lesions, the cortical approach would be more generally applicable, including in many cases of acute blindness
where the psychological distress is usually more important. Finally, the individuals general health should also be
considered because satisfactory candidates are usually
terminal cases of RP and therefore rather old while the
implantation surgery requires a prolonged anesthesia.
A complete assessment procedure must precede implantation.
A standard ophthalmologic examination is a good starting point. Because of the chronic nature of the condition,
the diagnosis should be checked according to up-to-date
knowledge. Some candidates have not had an ophthalmologic investigation for many years and only know that they
have an incurable eye disease. The blind patient could be
unaware of some additional eye problem or other interfering condition. A proper evaluation of the total degree of
blindness is necessary and objective tests, such a absent
VEP and ERG, are very useful for comparison with the
postimplantation evaluation.
Taking into account the heterogeneous nature of retinitis pigmentosa, this diagnostic label is not enough to
warrant the survival of ganglion cells in a given patient.
Eyelid surface stimulation is the technique of choice here.
A cathode is placed on the closed eyelid while an anode is
stuck on the heterolateral mastoid (50). Small current
VISUAL PROSTHESES
543
544
VISUAL PROSTHESES
VISUAL PROSTHESES
545
image, each pixel also carries luminance and color information. Although the phosphene perceptions generated can be
colored, no approach has hitherto developed means to control it and this dimension can therefore not be exploited. The
brightness of phosphene perceptions is modulated by the
stimulus intensity, but intensity also modulates the spatial
recruitment and therefore, localization and brightness are
not independent. In the optic nerve approach, strong stimuli
will yield only large phosphenes centrally located in the
visual field. With the retinal approaches a stronger stimulus
increases the perceived luminosity but is likely to stimulate
different structures and interfere with the neural code. In
the case of stronger stimuli on the visual cortex surface,
Brindley reported the appearance of additional phosphenes
and their persistence up to 2 min after the stimulus ceased.
Until now, epiretinal or optic nerve approaches do not
explicitly take into account matters, such as the existence
of ON as well as OFF ganglion cells. Stimulating more than
a single cell or axon perhaps leads to some cancellation of
their perceptive effect. In addition, the electrical stimulation
may interfere with ongoing spontaneous firing of the
ganglion cells. The link between stimulus and light perception can thus be expected to be rather complex.
The number of phosphenes that can be generated is still
by far not large enough to come to a realistic pixelization.
On the other hand, the central visual network does not
build an internal projection of the outside world images as
implied by such principles. The photosensors in the eye
capture images as pixels, but that is also where the pixel
structure stops. All other layers of the retina analyze and
encode the image according to many characteristics other
than a mere pixel position. Beyond a rough retinotopy, edge
enhancement, movement detection, and a few other known
features, the spatiotemporal encoding appears to be very
complex. Except for the subretinal approach, recreating a
natural image perception will require to interface a prosthesis with this complex and largely unknown code. This
hurdle is likely to be even more challenging for cortical
implants than for epiretinal or optic nerve approaches.
Another difficulty is that as long as a near perfect
perception will not be achievable, bilateral implantation
will not be able to convey distance information. Other
distance clues are also linked to a relatively high quality
vision. This means that before visual prosthesis reach a
very high degree of performance, indirect systems will be
required to provide the important distance information.
Another direction for future developments is set by the
need for image stabilization. The subretinal approach uses
the eye optics with the result that eye movements are
included in the normal physiological network of vision.
In all other approaches, an external camera is used. This
camera is attached to spectacles and follows head movements instead of eye movements. For a correct localization
of the surroundings, the prosthesis user must learn to
inhibit eye movements as far as possible and only use slow
head movement to scan the environment. This is of course a
severe limitation. Eye and head movement tracking methods will at some point be necessary to stabilize images. The
most advanced solution would be to implant or integrate a
miniature camera in the eye as well. A feedback system
taking into account eye movements in the image analysis
546
VISUAL PROSTHESES
BIBLIOGRAPHY
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VISUAL PROSTHESES
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32. Dobelle WH. Artificial vision for the blind. The summit may
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36. Weiland JD, Anderson DJ, Humayun MS. In vitro electrical
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37. Mahadevappa M, et al. Perceptual thresholds and electrode
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38. Humayun MS, Prince M, de Juan Jr. E, Barron Y, Moskowitz
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549
VOCAL REHABILITATION.
DEVICES.
See LARYNGEAL
PROSTHETIC
X
X-RAY EQUIPMENT DESIGN
MARTIN TORNAI
Duke University
Durham, North Carolina
INTRODUCTION
Radiography is a form of physical diagnosis in which X rays
are used to obtain medically useful information about a
patient. X rays are generated in a controlled way, and a
beam of X rays is passed through the patient. The differential absorption of ionizing X-ray radiation by different
tissues modulates this beam. The transmitted beam is
detected, and its information content is recorded. In addition, radiological imaging methods are used to control,
guide, and monitor both diagnostic and therapeutic manipulations such as needle biopsy, percutaneous transluminal
angioplasty (see CORONARY ANGIOPLASTY), and radiation therapy.
X-ray equipment is composed of many subsystems and
components, each of which presents unique choices and
tradeoffs for the equipment designer. These components
include means for X-ray production, spatial and spectral
shaping of the X-ray beam, patient handling, as well as
means for image detection and capture, intermediate
image handling, image processing, image display, and data
storage. Auxiliary equipment and logic are customarily
included in the design and construction of X-ray apparatus
for the control, synchronization, and automation of the
examination process. The X-ray equipment designer must
balance different and often conflicting requirements to
obtain an optimum solution for each examination category
or application. For example, fine spatial detail requires
minimization of both geometric blur (implying a fine focal
spot along with low power and low magnification) and
motion blur (implying short exposure time with high power
and a large focal spot). This leads to specialization of the
equipment for different medical applications. In addition to
clinical requirements, the apparatus must also be designed
to meet a wide variety of industrial and professional standards as well as comply with governmental regulations.
The functional organization of an X-ray imaging system
is shown in Fig. 1. In one form or another, these elements
are present in all X-ray imaging systems. This article will
follow the logical flow shown in Fig. 1, with emphasis given
to the material contained in the double-sided boxes.
Other articles in this Encyclopedia discuss the remaining
topics.
Power Components
The primary purpose of the power components in the
generator is to control the X-ray tube voltage, current,
and exposure time. The contrast and signal-to-noise ratio
(SNR) of a radiographic image, as well as dose delivered to
the patient, are partially controlled by adjustments of the
550
Power Components
(Single/Three Phase)
Generator
Console
Battery
551
Room/Facilities/CustomApps
X-ray Tube
Control and
Sychronization
(including AEC)
Beam Shaping and
Collimation
Patient
Detector
(and Controller)
Acquisition
Image
Processing
Display
Storage
from 110 V supplies. Single-phase and low-power threephase equipment typically operates using a 220 V line.
Higher power equipment may require 440/480 V.
An undesirable characteristic of some X-ray generators
is ripple, defined as the percent variation of voltage during
an X-ray exposure. A high ripple factor can result in
undesirable X-ray flux and spectral variations leading to
unpredictability in image quality and patient dose. Singlephase, full-wave rectified generators suffered from very
large ripple factors, and therefore they have been virtually
replaced by the constant potential generator for the most
demanding imaging applications, medical imaging being
one of them. Although these types of generators are generally larger, more complex, and expensive, they provide
extremely low (<5%) ripple factors, and they are essentially constant in their voltage output. These generators
typically use single- or three-phase 50/60 Hz line voltages of
220 V or higher. One common type of constant potential
552
Number of Photons
2.00E+07
80 kVp
100 kVp
1.50E+07
1.00E+07
5.00E+06
97
91
85
79
when an overheat signal is received from the tube. Additional tube details are provided in the following section.
X-Ray Tubes
The normal X-ray tube is a vacuum diode. Figure 4 is a
photograph of a typical X-ray tube housing as well as a
cutaway diagram of the typical interior tube components.
Electrons are generated by thermionic emission from the
filament of the tube. The electron stream is electrostatically focused onto a small target on the anode by means of a
carefully designed, shaped, and sometimes charged, highly
polished nickel cathode focusing cup.
X rays are produced by interactions between the electrons and the target (see X RAYS, PRODUCTION OF). Most
electrons emitted by the hot filament become current carriers across the tube. One can, therefore, set tube current
Timer T
H
H.V. Transformer
Auto
Transformer
A
kV
S
Figure 3. Schematic diagram of a single-phase, fullwave rectified generator. Feedback and stabilization
elements are not shown. X-ray tube voltage is
adjusted by setting the autotransformer before
exposure. Tube current is adjusted by setting
the filament voltage and hence its temperature.
A, Autotransformer; H, high-voltage transformer;
F, filament transformer; S, exposure switch; T,
radiographic timer; V, prereading voltmeter used
for kV indication.
73
67
61
55
49
43
37
31
25
19
13
0.00E+00
1
Exposure
switch
Filament
Transformer
X-ray tube
553
554
555
556
X-ray tube
Collimator
Bowtie
filter
Scatter
Patient
Grid
Detector
Figure 6. Schematic of the radiation trajectories and various
components of interaction in the X-ray generation and detection
system. Near the source is the source collimation apparatus. Distal
to the source, the radiographic grid consists of thin lead strips,
usually aligned with the focal length of the X-ray tube. Useful
imaging photons see narrow grid strips and wide interspaces.
Scattered photons see wider lead strips; hence, they are more
likely to be absorbed by the grid.
optimal performance of different radiographic examinations. For example, a slow film speed film with finer spatial
resolution may be more useful for extremity imaging of fine
bone fractures, whereas a faster speed film with coarser
resolution is more useful for chest imaging where stopping
or minimizing the influence of cardiac motion is desired.
There are both advantages and disadvantages to the
development and use of digital X-ray detectors, but a
primary advantage is that there is a decoupling of the
image capture and image display process. In addition to
separating image capture from image display, the digital
representation of the radiographic image is key to the
successful implementation of a picture archiving and communications system (PACS) system, which has already
shown to have a beneficial impact on the delivery of health
care. With advances in large-scale miniaturization and
packaging, and production of large-area electronics structures with high yield, there are continual advances in
production and manufacture of digital detectors with
increasingly finer spatial resolution. Indeed, there is a
projected 600% growth in demand of digital radiography
and digital mammography systems by 2008, along with
declining demand for screen-film and computed radiography (CR) systems sales. Digital systems are expected to
surpass other film-screen based X-ray imaging systems in
the near future. Nevertheless, a large number of these
systems currently exist and are part of contemporary
radiography.
Photostimulable phosphor systems were introduced
several years ago and remain popular in radiographic
practice. In a CR system, an image storage plate traps
an image of the attenuated X-ray distribution with excited
state electrons. When such a plate is scanned with a penciltip-sized laser beam, the electrons are de-excited and
return to their ground state with the emission of visible,
phosphorescent radiation. This phosphorescence can be
measured, digitized, and subsequently used to produce
an image (fluorescent scintillation systems and phosphorescent systems differ in the decay time t of the scintillation
event, where fluorescence occurs in t 109 s, and phosphorescence can be considerably longer, lasting t hours
or days). Such CR systems are capable of reproducing >1;
5 line per millimeter with an acceptable DQE. The phosphors used in these systems have a linear dose-to-photoluminescence response extending over several orders of
magnitude of absorbed dose. With proper reading technique,
this intrinsic linearity permits a decoupling of dose from
film blackening. Intentional or inadvertent exposure errors
can be compensated for by the reading electronics, thus
reducing retakes. Dose may be selected with regard to the
image quality requirements of the individual examination.
The X-ray-sensitive image intensifier, using charge
coupled devices (CCDs), is currently the universal image
receptor for fluoroscopy and fluorography (see IMAGE INTENSIFIERS). This device converts the modulated X-ray beam
into a minified visible light image projected onto a small,
fine resolution (cooled) CCD. The conversion factor (image
blackening per unit of X-ray input) of modern image
intensifiers is high enough that the quantum sink in most
imaging chains is the X-ray intensity detected and photoelectrons created at the tubes input screen. The DQE of
557
558
Figure 7. Timing diagram illustrating the necessity for synchronization when implementing an automated system that involves
many different system components, including X-ray generator,
digital detector, motion control devices, and frame grabbing devices.
559
spot film tower. The spot film device, located between the
patient and the image intensifier, is a specialized cassette
holder. Radiographic spot films, obtained during fluoroscopic
examinations, are captured using the spot film device and
conventional cassettes. The radiologist usually views the
fluoroscopic image by means of closed-circuit television or
on a computer screen. Fluorographic images are recorded
using camera systems directly focused on the output of the
image intensifier. The increasing use of fluoroscopic cameras
makes the conventional spot film device obsolete.
Angiographic and other interventional or special-procedure laboratories are highly specialized rooms with film
changers and cameras adapted to the needs of rapid imaging. Special procedures require especially easy access to
the patient by the staff as well as the capability for multiple
projection angles of the X-ray beam. The patients medical
condition and any attached life support devices dictate that
these examinations be performed with as little patient
handling as possible. In addition, the equipment should
provide adequate radiation protection for the staff. The
patient table and other mechanical equipment in these
rooms are therefore highly specialized to meet the needs
of different examinations. Under many circumstances, the
apparatus permits simultaneous radiography from two
directions (i.e., biplane imaging).
Tomographic imaging is another mechanically complex
procedure found in radiographic rooms. In a historical
tomographic apparatus, the film and X-ray tube were
synchronously moved so that overlapping structures in
the patient are removed. Tomographic apparatus ranged
from attachments to simple Bucky tables to dedicated
equipment capable of producing a wide variety of motions.
Contemporary computed tomography is still mechanically
complex, although manufacturers have gone to great
lengths to enable easy patient and technologist access in
a clutter-free system (see COMPUTED TOMOGRAPHY).
In radiotherapy, very high (MeV) tube potentials are
used for radiation of tumors. These systems may include a
separate but integrated keV imaging system for scouting
the area for treatment planning before irradiation. MeV
imaging systems are also being investigated for their ability to produce their own image without the need for a
separate keV system. In the past, direct film detection
was used because the incident energy and flux was high
enough to sufficiently expose film, but newer flat panel
digital devices are rapidly being adapted for this portal
imaging, MeV application. Designers must take these into
consideration.
Several other emerging areas including tomosynthesis,
small animal imaging, computed mammotomography, and
other dedicated or application-specific imaging technologies
are developing rapidly. Thus, it behooves the designer to
keep in mind potential future applications when considering
equipment selection options. The primary changes have
been rapidly occurring in imaging (i.e., detector) technologies, in moving from analog to digital systems, and the
Internet technology associated with their image processing,
sharing, and transfer. There are several initiatives to modify
the X-ray sources for both improved focal spot characteristics (e.g., smaller, faster, switching capabilities) and target
and filtration materials (i.e., for more optimal spectra used
560
in application specific imaging paradigms). To most appropriately synchronize and use these emerging, digitally
based technologies, computer-based, centralized data control and acquisition technologies need to keep pace with
these other emerging technologies. Only through properly
using and synchronizing these various necessary X-ray
system components can the lowest ionizing radiation doses
be applied to obtain images that provide the most information content available to the clinician, whose proper interpretation will affect the patient under observation.
FURTHER READING
Curry III TS, Dowdey JE, Murry Jr RC. Christensens Introduction
to the Physics of Diagnostic Radiology. 3rd ed. Philadelphia, PA:
Lea & Febiger; 1984. A general overview of the physics and
technology of diagnostic radiology. Many U.S. radiology residents use this book as their primary textbook and technical
reference.
Hendee WR, Chaney EL, Rossi RP. Radiologic Physics, Equipment
and Quality Control. Chicago, IL: Year Book Med. Publ.; 1977.
A textbook for advanced technologists.
Johns HE, Cunningham JR. The Physics of Radiology. 4th ed.
Springfield, IL: Thomas Publ.; 1983.
Beutel J, Knudel HL, Van Metter RL. Handbook of Medical
Imaging, Volume 1: Physics and Psychophysics. Bellingham,
WA: SPIE Press; 2000.
See also X-RAYS,
MEDIUM ENERGY.
X-RAY MAMMOGRAPHY.
See MAMMOGRAPHY.
INTRODUCTION
In order to improve or maintain an optimal achievable level
of healthcare, most medical facilities usually have some
type of quality assurance program. The quality assurance
programs encompass a variety of functions, such as development of comprehensive safety rules, establishment of
infection control guidelines, provisions for the efficient
management of critically ill patients, establishment of
accurate record-keeping functions, and the development
of adequate educational training for the staff (1). In radiology, a portion of the overall quality assurance program is
devoted to a quality control program for the X-ray equipment. The American College of Radiology (ACR) defines
quality control (QC) programs as a periodic monitoring of
aspects of the precision or accuracy of the X-ray equipment
pertaining to the successful performance of the equipment,
techniques, or tests rather than to the clinical decision
making (2). In general, QC involves equipment rather than
patient care.
The optimization of the image quality in radiology procedures is one of the most important reasons for QC
programs. The QC programs establish a test procedure
by which the image quality can be measured and establish
a standard level of image quality one attempts to maintain
(6). Thereafter, the image quality can be measured on a
regular basis and corrective actions are taken as necessary.
Degraded image quality can often hamper the proper
clinical diagnosis and thereby have a severe negative
impact on patient care. One would not like to deliver
radiation doses to the patients that result in limited or
no diagnostic information. Hence, a major goal of QC
programs in diagnostic radiology departments would be
the assessment of image quality.
Quality control programs must also attempt to maintain
a consistent level of equipment performance. X-ray outputs
that are not reproducible from one exposure to the next will
result in over- and under-exposed images. Unusable radiographs result in unnecessary patient radiation dosages,
delays in diagnosis and treatment, and economic losses in
terms of technologists and physicians time and film. Similarly, the technologists should be able to expect that adjacent rooms with similar X-ray equipment will have similar
X-ray outputs and similar calibrations within reasonable
tolerances attributed to differences in the models and
manufacturers designs of the equipment. Automated film
processors should be adjusted to produce similar radiographs regardless of where the films are developed. Similarly, digital X-ray imaging like Computed Radiography
(CR) and Digital Radiography (DR) must have consistent
X-ray exposures, image processing, and display of images.
Consistency of a given X-ray room and consistency in
comparing the various X-ray equipment is essential to
maintaining a standard level of radiographic image quality
for the entire facility.
Finally, economic considerations are a major impetus
for having an effective QC program. It has been estimated
that each radiographic film that must be repeated costs the
facility $35 (1986 prices) (7). The cost of repeated films
include items such as film prices, X-ray tube usage, X-ray
equipment depreciation, chemistry usage, processor depreciation, technologists and physicians time, and facilities
cost (rent, heat, and electricity). A study performed by the
federal government indicated that repeat rates can often be
decreased by a factor of two by effective QC programs (8,9).
Without QC programs, repeat rates can be expected to be
1016%; with QC programs, repeat rates can be expected to
be 58%. These repeat rates are due to patient motion,
positioning errors, or other technologists errors. Repeat
rates can often be drastically reduced by the usage of charts
in which the technical factors to be selected are listed for a
variety of patient procedures and patient sizes. The development of these technique charts should be considered to
be part of a good QC program. Furthermore, a good QC
program often identifies and corrects equipment malfunctions before they become serious and result in excessive
downtime of the equipment. Thus, a good QC program
usually provides cost savings to a X-ray facility that can
offset the cost of the program (10,11).
In summary, there are a number of good reasons for the
establishment of a QC program for a medical X-ray facility.
561
562
X-RAY TUBE
The X-ray tubes are the source of the X rays produced
in the X-ray equipment. Figure 1 shows a sketch of the
X-ray tube. Without exposure initiation, there is usually a
standby current passing through the filament. This current is sufficient to keep that filament warm, but it should
be less than that necessary for thermionic emission. There
are two or more different filaments. The larger filament is
used when more thermionic electrons are needed for
increased X-ray production. The use of larger filaments,
however, results in a larger area on the anode where the
electrons collide with the target; this area, as seen from the
position of the image receptor, is called the effective focal
spot. Large focal spot sizes can result in the degraded
image quality due to geometric blur. An important part
of a QC program, therefore, is the measurement of effective
focal spot size.
Just prior to making an X-ray exposure, the rotor preparation switch is depressed. This switch increases the
current through the filament so that sufficient electrons
are boiled off in order to yield the correct amount of electron
flow (tube current) between the cathode (filament) and the
anode (target). Simultaneously, the anode begins to rotate,
increasing to its correct speed. The rotation is needed to
distribute the heat created by electron bombardment of the
target. Upon depression of the exposure switch, the
selected high voltage in kilovolts (kVp) is applied between
the cathode and the anode. This voltage accelerates the
thermionics electrons from the filament and causes them to
hit the anode with high speed. The collisions result in X-ray
production. The lead lining attenuates X rays in all directions except in the region of the tube port where the lead is
missing. Some of the X rays do penetrate through the lead
shielding and they are called leakage radiation. This radiation must be measured to determine if it is within legal
limits. At the end of the exposure, the high voltage is
removed. The filament current then returns to the standby
level, and electromagnetic braking is provided to slow the
anode to a stop (1921).
Figure 1. Diagram of an X-ray tube assembly that depicts the major components.
563
564
the X-ray tube anode, arcing cable connections, malfunctioning milliampere stabilizer, phase imbalance in the
power line, rectifier failure, and other generator problems.
Modern radiation detectors usually have a BNC or computer output by which the radiation waveform can be
monitored. A coaxial cable can be connected to a storage
oscilloscope to record the radiation waveform (see Fig. 3). A
three-phase, 12-pulse X-ray tube unit usually exhibits a 5
10% ripple in the wave form; high frequency units have a
variable ripple (that depends on kVp and mA used) of
320%; a three-phase, 6 pulse unit usually exhibits 20
25% ripple; single-phase units exhibit 100% ripple. The
peak values of each of the pulses in the waveform, however,
should be relatively constant; the peak values should not
change by >7%. The display of spikes or dropouts in the
waveform are indicative of problems.
pu
d
180 m 1
565
566
Mammography
>(kVp/100) 0.03 mm Al
<(kVp/100) C mm Al
Where C 0.12 Mo/Mo, 0.19
Mo/Rh, and 0.22 Rh/Rh
>[2.26 (kVp/100)] 0.48 mm Al
Radiograph and
routine fluoro
Angiography and
cardiac fluoro
567
MILLIAMPERAGE ACCURACY
Another factor that influences the selected mAs is the
milliampere calibration. Again, inaccuracies among the
milliampere stations can result in improper radiographic
densities on the film. Moreover, it is desirable that various
rooms in a large X-ray department have a similar calibration. Therefore, technique charts for procedures throughout the department can be standardized.
568
Improper peak kilovoltage calibration of the X-ray generator has major influences upon image quality and patient
dose. High peak kilovoltages reduce patient contrast,
increase scatter, and increase subject latitude; they also
result in reduction of patient dose. Low peak kilovoltages
have the opposite effect. Moreover, miscalibration results
in non-uniform X-ray quality throughout a large X-ray
department. Thus, a standard for the determination of
peak kilovoltage accuracy is important.
There are a number of methods by which peak kilovoltage calibration can be measured. These methods
include high voltage bleeder resistor networks and noninvasive kVp meters (2629). A simple method often
utilized is noninvasive kVp meters, such as one shown
in Fig. 8. These meters are placed in the X-ray beam
and display a digital number for the measured peak kilovoltage. The meters contain several solid-state radiation
detectors, each with different amounts of copper filtration.
By measuring the amount of penetration of X-ray beam
through these filters the peak kilovoltage can be computed.
These noninvasive peak kilovoltage meters are usually
accurate to within 2 kVp. Even though more accurate
peak kilovoltage instrumentation exists, the relative ease
with which is noninvasive peak kilovoltage measurements
can be made is their principal advantage. It is recommended
that peak kilovoltage calibration be accurate to within
5% or 2 kVp, whichever is larger at all milliampere
MILLIAMPERE LINEARITY
The assessment of the relationship between the various
milliampere settings and their corresponding measured
X-ray output is called milliampere linearity. If the milliampere is increased by a factor of 2 with all other settings
unchanged, the X-ray output should also increase by a
factor of 2. If the milliampere settings on the control are
miscalibrated, the actual milliamperage will not increase
linearly with the selected values.
In order to make milliampere linearity measurements,
one merely places a radiation detector in the X-ray field
along the central ray. The detector is kept at a fixed
location. One peak kilovoltage and time setting is selected
(e.g., 80 kVp and 0.1 s). A series of fixed exposures are
measured for each of two (or more) different milliampere
settings (e.g., 200 and 400 mA). The average exposure
value for each of the 2 mA stations is calculated (E1 and
E2). The average exposures are divided by the mAs values
used to produce the exposures mGy per 100 mAs (or mR
mAs1). The term (X1 E1 mAs1) should be the same for
569
570
VISUAL INSPECTION
If possible, the grid should be removed from the bucky
assembly on an annual basis. It should be visually
inspected for damage and for spills of contrast material.
The focal distance and grid ratio marked on the grid should
be checked to determine if they are appropriate for the
intended radiographic procedures. It should also be determined that the correct side of the grid faces the X-ray tube;
inverted grids result in cutoff of image density toward the
edges.
GRID UNIFORMITY
In order to ascertain that there are no defects in the grid
and that there are no irregular cutoffs, a cassette should be
placed in the bucky tray and a rapid exposure made to
result in a film density of 1.20 du (or appropriate digital
image index number). Exposure times should be <20 ms in
order to stop grid motion. The developed film should have
uniform density throughout and the grid lines should be
visible. Irregularities in the grid lines or nonuniform density may be indicative of a grid problem.
BUCKY MOTION
Sometimes, the device that causes the grid to oscillate
during the exposure malfunctions or is not properly synchronized with the X-ray exposure. To test for bucky
motion, a cassette is placed in the bucky tray and an
exposure is taken with a longer exposure time selected.
Exposure times should be >100 ms. The developed image
should have a uniform density and grid lines should not be
visible. The bucky motion should blur all the grid lines on
the image. If the grid lines still appear, there is a problem
with the bucky motion.
CENTERS ALIGNMENT
The miscentering of the X-ray field and the center of the
image receptor cassette could result in the loss of diagnostic information. For this test, the detente and collimator
light systems are used to position the X-ray tube assembly
over the filmscreen cassette that has been placed in
the bucky tray. The X-ray field size must be smaller than
the cassette. An X-ray exposure of the cassette is made and
the centers of both the X-ray field and the image are determined. The misalignment of the center of the cassette with
the center of the X-ray field must be <2% of the distance
between the X-ray tube focal spot and the cassette (SID).
FLUOROSCOPIC X-RAY EQUIPMENT
Some of the components in fluoroscopic X-ray equipment
are similar to those in radiographic equipment. The same
X-ray generators are often used to operate several X-ray
tubes in a single radiology room; often a fluoroscopic and
radiographic X-ray tube are connected to the same X-ray
generator. However, in addition to the standard radio-
571
572
573
574
PINHOLE IMAGES
The angle through which the X-ray exposure is made
influences the thickness of the imaged tomography planar
sections. Moreover, it is important that the motion be
uniform and symmetric about a central point. All these
factors can be assessed through a pinhole image.
To do this test, a lead sheet with a small hole [(18 in.
(0.32 cm)] drilled in it should be suspended several inches
above the tabletop at the height of the focal plane. A film
screen cassette should be placed on the table top beneath
the hole in the lead sheet. With the X-ray tube at zero
degree tomo angle, the pinhole should be placed along the
central ray and a short exposure taken with no tomo
motion to mark this position. Then, a routine tomographic
exposure should be made and the cassette film developed.
The track on the film should be of uniform density and
symmetrical about the zero tomo angle point. The tomographic angle can be computed from the height of the
pinhole above the cassette (h) and the width of the track
on the film (W). For linear tomography, the tomographic
angle is given by the following equation:
u 2 tan1
W
2h
SLICE THICKNESS
TRAY TRANSMISSION
Since the patients lap is often situated beneath the
cassette tray, it is important that the back surface have
sufficient lead lining to significantly attenuate or block
the X-ray beam. A radiation detector should be used
to measure the amount of radiation transmitted during
typical mammographic exposures. It is recommended that
the transmission be <0.01% of the primary beam.
BODY-SECTION TOMOGRAPHIC EQUIPMENT
The purpose of the equipment is to image thin planar
sections through the patients anatomy using filmscreen
or CR cassettes. The X-ray tube and cassette move in
opposite directions about a pivot (or focal) plane to blur
objects outside this focal plane. The motion is done such
that the anatomy at a preselected depth in the patient will
remain in focus on the image receptor cassette. All other
anatomy outside the focal plane will be blurred by the
motion.
The QC procedures of these tomographic units should
include additional tests directed toward analyzing the tube
motion and the planar radiographs (36).
575
The contrast scale for any given CT scanner can be arbitrary. If calibrated properly, however, the CT number of air
should be 1000 and the CT number of water should be
zero. Compact bone should have a large positive value near
1000 or more. In this manner, an acceptable gray scale
will be established for the various anatomical substances
shown in scans of patients.
The contrast scale is the change in the effective attenuation coefficient per CT number unit. Usually, measurements are performed with reference to plexiglass and
water. The contrast scale (CS) is represented by the following equation:
CS
mplex mwater
CT No:plex CT No:water
mx mwater
CS
A number of references list the linear attenuation coefficients for air and compact bone. For 120 kVp, mair
0.000208 cm1 and mbone 0.414 cm1. For water, mwater
is usually taken to be 0.190 cm1. Hence, based upon the
measurement of CS, the CT numbers of air, water, and
bone can be estimated. Usually the CT units set air at
1000 and compact bone at 1000 HU. (Bone actually has
a wide range of CT number values due to the various
densities it may have in the human body.) A comparison
of the measured values with the ideal values indicates
whether the CS is satisfactory.
COMPUTER TOMOGRAPHY NOISE LEVELS
When one images a uniform material in a CT scanner, the
CT numbers for a localized region should all be the same. In
576
100 s CS
mwater
577
Fx A expa x e
This equation can be rearranged in order to determine the
value of a and e. The modulation transfer function (MTF)
can be computed directly using the value a (43).
LOW CONTRAST RESOLUTION
The CT scanner must not only be able to detect small
objects with high contrast, but it must also be able to image
small objects with low subject contrast. The difference
between normal tissue and pathology is usually small
differences in subject contrast (12% differences). A good
CT scanner should be able to detect small low contrast
lesions, that is, low contrast is more important than high
contrast resolution.
In order to test low contrast resolution, CT scans are
taken through a section in the phantom composed of a
plastic with CT numbers only slightly different from water.
This section contains various size holes of a slightly different plastic than the surrounding material. The contrast
between the plastic and the water is usually 0.40.6%. The
delectability is dependent upon the radiation dose used,
but it would be desirable to have low contrast discrimination of 46 mm holes at 0.50.6% contrast.
BEAM HARDENING
X-ray beams are polychromatic. Therefore, filtration
changes the X-ray spectrum and its effective energy. When
CT scanner X-ray beams pass through a lot of bone or long
paths through tissue, the X-ray spectrum is altered. The
effective linear attenuation coefficients for these hardened
X-ray beams change because attenuation is a function of
X-ray energy. Therefore, the CT numbers of tissue behind
extensive sections of bone may decrease appreciably due to
beam hardening. These effects are highly undesirable as
some tissues appear abnormal in CT number. This beam
hardening artifacts in CT numbers are undesirable.
In order to evaluate beam-hardening effects, 1 in.
(2.5 cm) diameter plastic rods with high attenuation coefficients are taped on the opposite sides of the surface of the
water section of a CT phantom. This section is scanned, and
the CT numbers along the line between the rods are
measured. CT scanners should be designed in a manner
that the water values are not depressed more than three
times the noise standard deviation.
578
The f-factor for acrylic is 0.78 cGy R1, and the f-factor
for tissue is about 0.92 cGy R1. The f-factor for air is
0.87 cGy R1. A weighted CTDI (CTDIW) is calculated
using (1/3) of the center value and (2/3) of the peripheral
value.
For these data, the actual radiation dose values can be
scaled using clinical setting of kVp, milliamperesecond,
and pitch. Pitch is the table movement between rotation
of the X-ray tube divided by the width of the X-ray beam.
The CTDIvolume is equal to the CTDIW divided by the pitch.
It is recommended that the CTDIvolume for clinical head CT
scans of patients be <6.0 cGy (rad) and that the body value
is <3.5 cGy (rad).
FILM PROCESSORS
Because the film processing affects the end product of film
screen radiographic images, this is one of the most important aspects of the QC program for diagnostic radiology.
Film processing conditions can affect film contrast, the
speed of the film-screen system, and base plus fog levels.
Indirectly, inadequate processing usually causes the technologist to alter kilovoltage or mAs that could result in an
increased dose to the patient.
In general, a 1 8F (0.6 8C) temperature change in the
developer chemistry produces a 0.030.07 density change
in the developed radiograph. The film density decreases for
a decrease in the developer temperature. For an 818 8F
(4.410 8C) decrease in the developer temperature, a 50%
increase in the patient exposure is necessary. Similarly,
increasing the developer temperature by 5 8F (2.8 8C) can
cause a latitude film to appear to have increased contrast.
Contamination of the processing chemistry also causes
changes in the film density and contrast. The magnitude
of the effects are dependent on the type of film, the kind of
chemistry, and the processor design.
In order to maintain consistency in the film development, a routine maintenance program for the processor
should be established. The replenishment rates should be
adjusted properly for the workload. The rollers should be
cleaned and inspected on a regular basis and the chemistry
should be changed as required. Moreover, steps should be
taken to minimize inconsistencies in the chemistry. Within
reason, all processors should operate from the same batch
of fixer and developer; this can be accomplished by mixing
large batches for delivery or using electronic mixers with
modular chemistry canisters.
The QC program for processors should utilize daily
sensitometry strips that are run through each processor
(44). In conjunction with the sensitometry, the processor
replenishment rates and temperatures should be checked.
Light sensitometers are recommended for making the
sensitometry strips (45,46) (see Fig. 12). The film used
for sensitometry should be the fastest high contrast film
routinely used in the facility. Since variations can be
found in different film emissions batches of the same kind
of film, strips from both old and new emulsion batches
should be run simultaneously during transition periods.
The processed sensitometry strips should have the densities measured with a densitometer. A sensitometer step
with a density 1.0 du above the base plus fog level should
be selected as the speed point. The difference in densities
of two points in the linear portion of the characteristic
curve should be used to determine a contrast index.
The base plus fog level on the sensitometry strips should
also be measured. These three parameters should be
compared to optimal values supplied by the film manufacturer and average values should be established for the
facility. The speed point should not be allowed to change
by more than 0.15 du about the average value. The
contrast index should not change more than 0.15 units.
Since the base plus fog is not very sensitive to variations, a
small change is indicative of significant abnormalities in
the processing. With good maintenance and QC procedures, the film processors should be very stable and
consistent.
DIGITAL IMAGE RECEPTORS
Digital image receptors could be either CR Cassettes with
their electronic readers or DR image receptors (47). With
both systems, a QC program should be routinely implemented to ensure consistency, identify artifacts and evaluate physicians display monitor (48). Most CR and DR
579
Figure 13. Radiographic image of an ACR Mammography phantom showing fibrils, calcium, speck group, and simulated masses.
systems have an index number to ensure sufficient radiation is utilized to avoid excessive quantum mottle. The QC
program should assess that the AEC is properly adjusted to
maintain proper radiation exposure. For CR systems, cassette should be exposed to measure spatial linearity, spatial resolution, uniformity of density and proper size and
collimation. Both CR and DR units should be evaluated for
artifacts and dirt. The physicians review video monitor
should be checked with a video pattern such as the SMPTE
(Society of Motion Picture & Television Engineers) for low
contrast visibility, spatial linearity, spatial resolution and
a reasonable contrast scale. A light meter can then be
employed to ensure that maximum luminance and contrast
scale are adjusted similarly on all video monitors (Fig. 13).
SUMMARY
There are numerous reasons for providing a QC program in
diagnostic radiology. Quality control is mandated by several regulatory agencies; hence a radiology facility must
demonstrate that some type of QC is being performed.
Another reason for QC programs is to ensure electrical,
mechanical and radiation safety for patients and staff.
Moreover, the QC program should provide better image
quality and a consistency in the radiographs. Finally, the
QC program should result in financial savings and
improved equipment performance.
The effectiveness of the QC program will depend on the
extent of testing performed. A cursory QC program is
usually conducted to just meet minimum regulatory
requirements. A more extensive program will attempt to
establish and maintain a high standard for equipment
performance.
Because of the diversity in the diagnostic equipment,
the QC program should be directed toward evaluating the
special features of each type of equipment. Hence, there are
1. Joint Commission on Accreditation of Hospitals. Accreditation Manual for Hospitals. Chicago, IL. Available at http://
www.JCAHO.org. 2005.
2. American College of Radiology (ACR). Standards. Reston
(VA) ACR, 20012002 or http://www.acr.org.
3. U.S. Department of Health, FDA, Center for Devices &
Radiological Health (CDRH). Routine Compliance Testing
Procedures for Diagnostic X-ray Systems. Available at http://
www.fda.gov/cdrh/radhlth/xraytestproc.html 2003.
4. U.S. Department of Health, FDA, Center for (CDRN) Devices
and Radiological Health (CDRN). Mammograph facility survey, equipment evaluation and medical physical qualification
requirements under MQSA. Available at http://www.fda.gov/
cdrh/dmqrp/6409.pdf 2000.
5. U.S. Department of Health, FDA, Center for Devices and
Radiological Health (CDRH) Resource manual for compliance
test parameter of diagnostic X-ray systems. Available at
http://www.fda.gov/cdrh/comp/rad_medical.html 2005.
6. Ostinelli A, et al. Quality assurance in diagnostic radiology:
Practical outcomes. Rad. Medica Oct 2003;106(4):413419.
7. Noyes RS. The economics of quality assurance. Radiol/Nucl
Med Mag Dec 1980.
8. U.S. Department of Health, Education and Welfare. Quality
assurance programs for diagnostic radiology facilities (FDA)
80-8110, Washington (DC): U.S. Govt. Printing Office; 1980.
9. Peer S, et al. Comparative reject analysis in conventional
film-screen and digital storage phosphor radiography. Rad
Protection Dosim 2001;94(1-2):6871.
10. Nelson RE, Barnes GT, Wittten DM. Economic analysis of a
comprehensive quality assurance program. Radiol Technol
1997;49:129134.
11. Fields T, Griffith CR, Hubbard LB. What price quality? A
quality assurance program for diagnostic radiology. Appl
Radiol JanFeb 1980;5764
12. U.S. National Council on Radiation Protection and Measurements (NCRP). NCRP Report No. 99 quality assurance for
diagnostic radiology, Bethesda (MD); 1980.
13. Waggener RG, Wilson CR, editors. Quality Assurance in
Diagnostic Radiology. New York: American Institute of Physics; 1980.
14. Gray JE, Winkler NT, Stears J, Frank ED. Quality Control in
Diagnostic Imaging. Baltimore: University Park Press; 1983.
15. American College of Radiology (ACR). Accreditation Programs (Mammography, MRI, CT, Fluoroscopy and Ultrasound). Available at http://www.acr.org. 2005.
16. American Association of Physicists in Medicine (AAPM).
Quality Control in Diagnostic Radiology. Madison (WI): Medical Physics Publishing; 2002.
17. Hospital Physicists Association. Quality Assurance Measurements in Diagnostic Radiology. Rep. No. 29, London:
HPA; 1979.
18. U.S. Department of Health, Education and Welfare. Regulation for the administration and enforcement of radiation
control for health and safety act of 1968. (FDA) 758003,
Washington (DC): U.S. Govt Printing Office; 1976.
19. Seibert JA, Barnes GT, Gould RG. Specifications, Acceptance
Testing and Quality Control of Diagnostic X-ray Equipment.
New York: Springer-Verlag; 1997.
580
44. Gray JE. Photographic quality assurance in diagnostic radiology, nuclear medicine and radiation therapy. Vols. 1 and 2
(FDA) 76-8043 and (FDA) 77-8018, Washington (DC): U.S.
Govt Printing Office; 1976.
45. Blendl C, Buhr E. Comparison of light and x-ray sensitometric response of double emulsion films for different processing conditions. Med Phys Dec 2001;28(12):24202426.
46. Nickoloff EL, Leo F, Reese M. A comparison of five methods of
monitoring the precision of automated X-ray film processors.
Radiology 1978;129:509514.
47. Rowlands JA. The physics of computed radiography. Phys
Med Biol Dec 2002;47(23):R123R166.
48. Samei E, et al. Performance evaluation of computed radiography systems. Med Phys March 2001;28(3):36137l.
See also CODES
INTRODUCTION
X-rays were used to treat cancer patients within a year of
their discovery by Wilhelm Roentgen in November 1895
(1). However, it was not until the invention of the hot
cathode tube by Coolidge in 1913 that X-ray beams could
be delivered in a stable manner and, hence, the output
controlled and measured with any precision. Further
improvements in the accuracy of X-ray beam dosimetry
occurred with the publication of the first central-axis depth
dose tables in 1922 (2) and with the definition of the
Roentgen and its use as a standard unit for X-ray dosage
in 1928 as recommended by the Second International
Congress of Radiology in Stockholm, Sweden.
In those early years, the energy of X-ray beams was
limited to 140 kV, and therefore only relatively superficial
lesions could be successfully treated. The situation was
improved in the early 1920s as higher energy (up to 400 kV)
X-ray units became available to permit the treatment of
deep-seated lesions (3). Since cobalt-60 treatment units
(average g-ray energy 1.25 MeV) came into use in the
late 1950s and electron linear accelerators capable of producing high energy (4 MeV), X rays in the early 1960s, the
use of kilovoltage X-rays in radiation therapy has drastically declined for deep-seated tumors.
The use of low energy X rays for the treatment of
superficial lesions is still popular, even though the use
of electrons has replaced them for treating such lesions in
581
582
to pass through with little attenuation. This type of shielding design for therapeutic tubes is called a hooded anode.
The X-ray tube is enclosed in an oil shield that serves two
purposes: (a) to cool the tube and (b) to attenuate stray X rays.
Many major manufacturers have ceased manufacturing
kilovoltage X-ray therapy units (5). The three currently
available orthovoltage treatment units are Therapax
DXT300 manufactured by Pantak, Inc. (East Haven,
CN) and Gulmay D3300 and Gulmay D3225 manufactured
by Gulmay Medical Ltd. (Mississauga, ON). The same two
vendors also produce two superficial therapy units, Therapax HF 150 and Gulmay D2000. Some kilovoltage units
are no longer available, but are still in wide use, such as the
Philips RT-250 and RT-305 units and the Siemens Stabilipan. The most popular contact unit still in clinical use is
the Philips RT-50, formerly manufactured by Philips Medical Systems (Shelton, CN). A new, and novel, contact
therapy device available is the Photon Radiosurgery System, Model PRS400, manufactured by Photoelectron Corp.
(Lexington, MA).
Orthovoltage Units
Most orthovoltage units operate at 200300 kV with a tube
current of 1020 mA and have various filters to provide
beams with half value layers (HVL) between 1 and 4 mm
Cu. The X-ray generators used in these units may be single
phase, that is, self-rectified or half-wave rectified, or may
employ a Villard-type voltage-doubling circuit or a constant potential circuit (6). The constant potential circuit
maintains the accelerating potential at a nearly constant
value so that X rays can be produced continuously rather
than in pulses. This type of circuit allows for treatments at a
shorter treatment time with a higher average X-ray energy.
The energy absorbed by the anode of an X-ray tube is
proportional to the product of tube current, accelerating
potential, and operating time. For orthovoltage units, which
may be operated continuously at high tube voltages, the
anode must be cooled efficiently. The copper anodes of orthovoltage units are usually massive to serve as heat conductors. Oil circulated cooling is used instead of water circulated
cooling, as shown in Fig. 2 (7), where a hollowed-out anode
Oil circulation
X rays
Figure 2. The anode of an orthovoltage X-ray tube. The back of
the anode is hollowed out to permit oil circulation.
Contact Units
Expansion bellows
583
Oil shield
X-ray tube
Figure 4. The cooling system for superficial X-ray tubes. Water
circulates through the pipe NN0 to remove the heat from
the oil.
584
are mainly used for treating tumors close to the skin. The
primary point of interest is the dose near the surface rather
than at greater depths. Another reason is that it is more
convenient to perform routine beam calibration free in air
than in a water phantom.
The American Association of Physicists in Medicine
(AAPM) recommended that both methods be used for
absorbed dose determination for orthovoltage X-ray beams
depending on the measurement point of interest (9). To
improve measurement accuracy, the in-air method should
be used if the primary point of interest is at the phantom
surface. On the other hand, if one is more interested in the
dose at large depths than at the surface, the in-phantom
method should be used. Better agreement in measured
PDD curves at depth 1 cm and greater can be achieved
when they are normalized to the values at the 2 cm
reference depth than normalized to the surface values.
The AAPM recommended that only the in-air method be
used for superficial X-ray beam dosimetry (9).
Measurement Equipment
Phantoms. Water is the recommended phantom material when the in-phantom method is used in orthovoltage
X-ray beam dosimetry (9). Conversion factors are used to
convert from the air kerma in the sensitive chamber cavity
to the dose to water. Plastic phantoms are not recommended for in-phantom reference dosimetry for orthovoltage X rays as the chamber correction factors and
conversion factors to derive dose at a depth in water for
these phantoms are poorly known. Some water equivalent
plastics are commercially available for orthovoltage X-ray
measurements. However, their properties must be investigated before they can be used as water substitutes.
Dosimeters. Air-filled ionization chambers are recommended for kilovoltage X-ray beam reference dosimetry (9).
Measurements for orthovoltage X rays are performed
either free in air (in cases where the surface dose is the
primary concern) or at a 2 cm depth in water (dose at
greater depths is the primary concern). Cylindrical chambers that have a calibration factor varying with the beam
quality by <3% in this energy range are recommended for
the beam output measurement. For superficial X rays, only
the in-air method is used. Cylindrical chambers that have a
calibration factor varying with the beam quality by <5%
between 50 and 150 kV are recommended. Extensive studies have been carried out on the correction factors for the
commonly used Farmer-type chambers for the in-phantom
measurement (1621). Other cylindrical chambers may
also be used. However, correction factors must then be
determined by comparing these chambers with a chamber
with known correction factors. If measurements are performed in water, a thin waterproofing sleeve should be
used and appropriate correction factors should be applied
depending on the material and thickness used. If measurements are made in air, the thimbles of cylindrical chambers
are thick enough, so no build-up cap is required. For X-ray
energies <70 kV, calibrated parallel-plate chambers with a
thin entrance window are recommended. Thin plastic
build-up foils should be added to the entrance window, if
585
50
60
70
80
90
100
1.5
3.0
4.7
6.6
8.7
10.9
Kair
M
(1)
X
M
(2)
586
mm Cu
men =rw
air (free-in-air)
0.1
0.3
0.5
0.8
1.0
3.0
5.0
1.047
1.046
1.044
1.044
1.035
1.028
1.022
1.020
1.021
1.029
1.045
1.020
1.035
1.050
1.068
1.076
1.100
1.109
0.03
0.05
0.08
0.10
0.3
0.5
0.8
1.0
3.0
5.0
8.0
(5)
587
Table 3a. Water Kerma-Based Backscatter Factors, Bw, for Different Field Diameters (d) and SSD for Superficial X Rays
HVL, mm Al
SSD (cm)
d (cm)
0.03
0.05
0.08
0.1
0.3
0.5
0.8
1.0
3.0
5.0
8.0
20
1
3
5
10
15
20
1.005
1.005
1.005
1.005
1.006
1.006
1.007
1.008
1.008
1.008
1.008
1.008
1.011
1.014
1.014
1.014
1.014
1.014
1.014
1.019
1.019
1.019
1.019
1.019
1.028
1.049
1.054
1.057
1.058
1.058
1.036
1.069
1.080
1.088
1.090
1.091
1.043
1.092
1.112
1.129
1.133
1.136
1.046
1.105
1.131
1.155
1.162
1.165
1.061
1.158
1.215
1.291
1.321
1.334
1.058
1.165
1.234
1.334
1.380
1.402
1.053
1.158
1.236
1.354
1.414
1.444
30
1
3
5
10
15
20
1.005
1.005
1.005
1.006
1.006
1.006
1.007
1.008
1.008
1.008
1.008
1.008
1.011
1.014
1.014
1.014
1.014
1.014
1.015
1.019
1.019
1.019
1.019
1.019
1.027
1.048
1.053
1.057
1.058
1.058
1.035
1.069
1.079
1.088
1.091
1.091
1.043
1.093
1.111
1.130
1.136
1.138
1.047
1.107
1.130
1.157
1.165
1.169
1.063
1.164
1.221
1.298
1.332
1.350
1.059
1.168
1.242
1.350
1.403
1.428
1.053
1.158
1.237
1.367
1.434
1.472
50
1
3
5
10
15
20
1.005
1.005
1.005
1.006
1.006
1.006
1.007
1.007
1.007
1.007
1.007
1.007
1.011
1.013
1.013
1.013
1.013
1.013
1.014
1.018
1.018
1.018
1.018
1.018
1.027
1.049
1.054
1.057
1.058
1.058
1.035
1.070
1.081
1.091
1.093
1.094
1.042
1.093
1.113
1.134
1.140
1.142
1.045
1.106
1.132
1.159
1.169
1.173
1.065
1.163
1.226
1.309
1.346
1.363
1.059
1.169
1.241
1.352
1.411
1.443
1.052
1.160
1.242
1.375
1.448
1.493
100
1
3
5
10
15
20
1.005
1.005
1.006
1.006
1.006
1.006
1.007
1.008
1.008
1.008
1.008
1.008
1.011
1.014
1.014
1.014
1.014
1.014
1.014
1.019
1.019
1.019
1.019
1.019
1.028
1.050
1.055
1.058
1.059
1.059
1.036
1.070
1.082
1.091
1.094
1.095
1.042
1.092
1.113
1.134
1.140
1.143
1.044
1.104
1.131
1.158
1.169
1.172
1.062
1.163
1.225
1.311
1.354
1.375
1.059
1.169
1.240
1.351
1.417
1.451
1.053
1.162
1.243
1.381
1.460
1.508
dependence or large experimental uncertainties. Welldesigned cylindrical chambers have nearly constant
energy response in this beam quality range and are suitable for in-phantom measurements. However, the mea-
Table 3b. Water Kerma-Based Backscatter Factors, Bw, for Different Field Diameters (d) and SSD for Orthovoltage X rays
HVL, mmCu
SSD (cm)
d (cm)
0.1
0.3
0.5
0.8
1.0
3.0
5.0
20
1
3
5
10
15
20
1
3
5
10
15
20
1
3
5
10
15
20
1
3
5
10
15
20
1.061
1.158
1.214
1.290
1.320
1.333
1.063
1.164
1.220
1.297
1.330
1.348
1.065
1.163
1.225
1.308
1.345
1.361
1.062
1.163
1.224
1.310
1.353
1.373
1.055
1.168
1.242
1.352
1.407
1.434
1.056
1.169
1.242
1.363
1.417
1.446
1.054
1.170
1.247
1.367
1.433
1.471
1.055
1.170
1.245
1.370
1.447
1.490
1.053
1.155
1.233
1.353
1.415
1.447
1.052
1.155
1.235
1.367
1.438
1.478
1.052
1.157
1.240
1.376
1.452
1.499
1.052
1.160
1.241
1.383
1.463
1.513
1.048
1.147
1.219
1.339
1.403
1.436
1.047
1.146
1.221
1.347
1.422
1.464
1.047
1.148
1.226
1.360
1.446
1.495
1.047
1.150
1.227
1.369
1.458
1.516
1.045
1.140
1.209
1.326
1.389
1.421
1.044
1.139
1.211
1.332
1.405
1.446
1.045
1.140
1.214
1.344
1.428
1.478
1.045
1.142
1.217
1.353
1.441
1.499
1.024
1.082
1.127
1.204
1.251
1.278
1.024
1.084
1.130
1.214
1.270
1.302
1.025
1.084
1.131
1.222
1.285
1.325
1.025
1.085
1.132
1.226
1.291
1.334
1.018
1.057
1.088
1.141
1.174
1.194
1.018
1.055
1.087
1.147
1.189
1.213
1.018
1.057
1.089
1.152
1.195
1.226
1.018
1.057
1.090
1.155
1.204
1.237
30
50
100
588
mm Al
men =rw
air
0.1
0.3
0.5
0.8
1.0
2.0
3.0
4.0
5.0
2.9
6.3
8.5
10.8
12.0
15.8
17.9
19.3
20.3
1.026
1.037
1.046
1.055
1.060
1.081
1.094
1.101
1.105
Table 5. Overall Chamber Correction Factors PQ,cham for Commonly used Cylindrical
Chambers in Orthovoltage X-Ray Beamsa
Chamber Type
HVL, mm Cu
NE2571
Capintec PR06C
PTW N300 01
NE2611 or NE2561
0.10
0.30
0.50
0.80
1.0
2.0
3.0
4.0
5.0
1.008
1.023
1.025
1.024
1.023
1.016
1.009
1.004
1.002
0.992
1.008
1.010
1.010
1.010
1.007
1.005
1.003
1.001
1.004
1.021
1.023
1.022
1.021
1.015
1.010
1.006
1.002
0.995
1.017
1.019
1.018
1.017
1.011
1.006
1.003
1.001
The data applies to the in-phantom method for a chamber at 2 cm depth in water and a 100 cm2 field.
Table 6. Correction Factors for PMMA Sheaths When Using Cylindrical Chambers for
In-Water Measurements in Orthovoltage X-Ray Beamsa
HVL
PMMA (Lucite)
(mm Cu)
(mm Al)
t 0.5 mm
t 1 mm
t 2 mm
t 3 mm
0.1
0.3
0.5
0.8
1.0
2.0
3.0
4.0
5.0
3.0
6.1
8.5
11.0
12.1
15.2
17.6
19.4
20.9
0.998
0.998
0.999
0.999
1.000
1.000
1.000
1.000
1.000
0.995
0.997
0.998
0.998
0.999
1.000
1.000
1.000
1.000
0.991
0.994
0.996
0.997
0.998
1.000
1.000
1.000
1.000
0.986
0.991
0.994
0.996
0.997
0.999
1.000
1.000
1.000
589
limits are established during the initial machine commissioning period before the system is first used for treating
a patient and thereafter annually, or after any change
which may significantly alter the dosimetry data and
the mechanical limits. Once the baseline is established,
maintaining the baseline data becomes the mission of
the dosimetry QA program. Documentation for each full
yearly calibration is maintained for 5 years after the
completion of calibration. Documentation of weekly and
monthly spot check measurements is maintained for
2 years.
The test frequency of each mechanical component and
dosimetry data for a treatment machine is determined by
the significance of the tests that indicate beam dosimetry
changes and mechanical tolerance changes within the
limited amount of time. Unlike clinical linear accelerators,
the number of combinations of energy and filter for a
kilovoltage X-ray machine are high, but only a few combinations are used on a routine basis. The number of patients
that are treated using kilovoltage X-ray beams are much
less than for megavoltage radiotherapy. Therefore, the
check of the beam dosimetry should depend on the frequency of the beam usage. The dosimetry QA items and
their frequencies are summarized below:
Daily Checks.
Beam output constancy for energy and filter combinations in use.
Functionality of the audiovisual monitor.
Door and energy interlock circuits and emergency
stops.
Monthly Checks.
Annual Checks.
BIBLIOGRAPHY
1. Glasser O, editor. The Science of Radiology. London: Bailliere; 1933.
590
25. Ma C-M, Li XA, Seuntjens J. Consistency study on kilovoltage x-ray beam dosimetry for radiotherapy. Med Phys
1998;25: 23762384.
26. Central axis depth dose data for use in radiotherapy. Br J
Radiol (Suppl) 1996; 25.
27. Podgorsak EB, Gosselin M, Evans MDC. Superficial and
orthovotage
x-ray
beam
dosimetry.
Med
Phys
1998;25:12061211.
28. Gerig L, Soubra M, Salhani D. Beam Characteristics of the
Therapax DXT-300 orthovoltage therapy unit. Phys Med Biol
1994;39:13771392.
29. Butson MJ, Mathur J, Metcalfe P. Dose characteristics of a
new 300 kVp orthovoltage machine. Aust Phys Eng Sci Med
1995;18:133138.
30. Aukett RJ, Thomas DW, Seaby AW, Gittins JT. Performance
characteristics of the Pantak DXT-300 kilovoltage X ray
treatment machine. Br J Radiol 1996;69:726734.
31. Kurup RG, Glasgow GP. Dosimetry of a kilovoltage radiotherapy x-ray machine. Med Dosimetry 1993;18:17986.
See also COBALT 60 UNITS FOR RADIOTHERAPY; RADIATION DOSIMETRY FOR
ONCOLOGY; RADIOTHERAPY, INTRAOPERATIVE.
INTRODUCTION
X-ray interaction with matter forms the backbone of medical physics. The basic interaction and its applications can
be found in many subfields of medical physics. Some of the
more common examples are applications in diagnosis and
treatment of cancer, shielding design of accelerators,
radiation detectors, biological response to radiation, and
radiation protection. A thorough understanding of the
interaction process is therefore mandatory to appreciate
many exciting phenomena encountered in medical physics.
Although the title of this article refers to X-ray interaction
with a medium, the physics of the process applies equally
well to gamma (g) rays. Furthermore, in this article, all
electromagnetic radiation is referred to as photons regardless of whether their origin is atomic (X rays) or nuclear
(g rays). How a given photon will interact with matter
depends on the energy of the photon and not on its birthplace.
When a beam of X rays passes through the medium, it
undergoes attenuation or loss of intensity. In other words,
some photons are removed from the beam. This attenuation may be due to either absorption or scattering of
photons by the medium. In absorption, the energy of the
photon is completely transferred to the atoms, whereas in
scattering, the X-ray beam undergoes a change in direction
that may be accompanied by a change in its energy. In both
absorption and scattering, the net result is the transfer of
energy to the medium. The amount of energy deposited per
unit mass of the medium is called dose (measured in the SI
unit, gray, 1 Gy 100 cGy), which is an important quantity in radiotherapy applications. How much energy will be
transferred to the medium depends on the medium composition and the energy of X rays.
X-ray energy transfer to the medium is a two-step
process. First, incident photons interact with the medium
and release electrons. Next, in traveling through the medium, these electrons lose their energy via excitation or
ionization of atoms. Therefore, photons are labeled as
indirectly ionizing radiation, in contrast to charged
particles, such as, electrons that are directly ionizing.
It is the latter that act as a vehicle for photon energy
transfer to the medium. If the electrons have sufficient
energy, they may also eject secondary electrons from atoms
that form their own tracks known as d rays.
591
N
A
N
At
EN dE
dN
hn
A
dA
dA
EN dC
At
dt
Photon Attenuation
Linear Attenuation Coefficient (m). Suppose that a
monoenergetic beam consisting of N0 photons is incident
on an attenuator of thickness x (Fig. 1). The number of
photons N that will pass through the attenuator and get
registered by the detector may be written as
N N0 emx
(1)
Detector
N0
N
592
interact in the absorber medium. The attenuation coefficient is a function of both the absorber material and the
incident photon energy. As the incident beam is assumed
to be monoenergetic, m is a constant. Because mx must be a
dimensionless number, when x is expressed in centimeters,
the linear attenuation coefficient m has units of 1/cm.
Equation 1 may also be written in terms of the beam
intensity:
I I0 emx
(2)
HVL is a measure of the penetrability of the beam: a highenergy X-ray beam (with low m) will have a large HVL.
Tenth Value Layer. The tenth value layer (the thickness
of the absorber required to reduce the transmitted intensity to one tenth of the original intensity) or TVL can be
written as
TVL
ln 10 2:302
3:323HVL
m
m
(4)
(3)
The beam generated from an X-ray tube or a linear accelerator is not mono-energetic, but it is composed of a spectrum of energies. The average energy of such a beam of
photons is approximately one third of the maximum photon
energy. When this poly-energetic beam passes through the
absorber, it is the low-energy X rays that are absorbed or
filtered out first. After the low-energy photons have been
removed, the filtered beam becomes more energetic or
harder. As the filter thickness increases, the average
energy of the beam increases. Therefore, for an X-ray
beam, the plot of beam intensity versus absorber thickness
is not quite a straight line (Fig. 3). Instead, we see that the
first HVL in the absorber is smaller than the second HVL;
the second HVL is smaller than the third HVL, and so on.
ln 2 0:693
m
m
1
m
(5)
(6)
wi
(7)
r
r i
i
where wi is the fractional weight of the ith element in the
mixture.
As photon beam attenuation depends on the number of
electrons and atoms in the path of the beam, the corresponding attenuation coefficients can be defined as follows.
Electronic Attenuation Coefficient. When the absorber
thickness is expressed as electrons/squared centimeter,
the corresponding attenuation coefficient is the electronic
attenuation coefficient. If Ne is the number of electrons/
gram, then
m 1
m
A
(8)
me
r Ne
r NA Z
where A is the atomic mass number, Z is the atomic
number, and NA is the Avogadros number 6.02
1023 atoms per atomic weight in grams. The electronic
attenuation coefficient, me (expressed in squared centimeter/electron) represents the probability that an incident
photon will have an interaction with an electron in the
absorber. As Z/A 0.5 for all materials (except hydrogen),
the number of electrons/gram is a constant for all materials: Ne (NAZ/A) 3 1023 (Table 1). As we will see
593
Density (g/cm3)
Hydrogen
Carbon
Oxygen
Aluminum
Copper
Lead
0.0000899
2.25
0.001429
2.7
8.9
11.3
Atomic
Number (Z)
Number of
Electrons/Gram
1
6
8
13
29
82
6.00
3.01
3.01
2.90
2.75
2.38
1023
1023
1023
1023
1023
1023
Effective Z
Fat
Muscle
Water
Air
Bone
0.916
1
1
0.001293
1.85
5.92
7.42
7.42
7.64
13.8
3.48 1023
3.36 1023
3.34 1023
3.01 1023
3.00 10 23
(9)
r Ne
r NA
The atomic attenuation coefficient ma is expressed in
squared centimeter/atom, when the absorber thickness is
in the units of atoms/squared centimeter.
We now look at each interaction in more detail.
COHERENT OR RAYLEIGH SCATTERING
Coherent scattering refers to the elastic scattering of a
photon beam with atomic electrons, in which no energy
transfer to medium takes place. The incident photon interacts with bound electrons as a whole (hence called coherent
scattering). The electrons are temporarily set in motion
(or oscillation) by the photons electromagnetic field, and
they return back to their original state by emitting a
photon with the same energy as the incident photon
(Fig. 4). The incident photon energy is too small to break
free any electron from its shell. The scattered photon is
emitted at a small angle relative to the incident photon.
When a single electron from an atom participates in the
process, the reaction is called Thomson scattering.
594
(10)
The probability that a photon will undergo photoelectric effect depends strongly on its incident energy E hn
and the atomic number Z of the absorbing material. In
fact, the photoelectric mass attenuation coefficient t/r
varies directly as the cube of atomic number and inversely
as the cube of photon energy (Z3/E3). Figure 6 shows a plot
of t/r versus energy for water (Z 7.5) and lead (Z 82).
Due to the Z3 dependence, a photon is 1000 times more
likely to undergo photoelectric interaction in lead than in
a water-like medium (e.g., tissue). Also, if it has sufficient
energy to knock out an electron, a low-energy photon is
more likely than a high-energy photon to participate in
the photoelectric effect. It can be observed from the figure
that as the photon energy increases, the probability of
photoelectric interaction decreases rapidly (as 1/E3). The
curve for lead also shows sharp discontinuities for incident photon energies of 15 keV and 88 keV. These peaks
correspond to the binding energies of L- and K-shells,
respectively, for lead and are called absorption edges. A
photon having energy less than the electrons binding
energy cannot undergo a photoelectric effect with electrons in that shell. However, as soon as the photon energy
exceeds the binding energy of the electron, the probability
of the photoelectric effect increases dramatically (like a
resonance) and a sudden jump (or discontinuity) is
observed in the plot of photoelectric attenuation coefficient versus energy. The discontinuity is greatest for the
K-shell and becomes weaker for higher shells (L, M, N,
etc.). Therefore, it is noticed that the most tightly bound
electrons have the greatest chance of undergoing photoelectric interaction. For water, the plot of t/r again shows
the same steady decline with energy, although the curve
is much smoother. As the K-shell binding energy for a low
Z medium is only about 0.5 keV, no discontinuities are
observed.
The above behavior of the photoelectric effect has many
important applications in medical physics:
3
595
can be obtained:
a1 cos u
1 a1 cos u
1
hv0
1 a1 cos u
cot f 1 atan u=2
E hv0
(11)
(12)
596
PAIR PRODUCTION
A photon with energy more than 1.02 MeV may interact
with the medium through pair production. In this reaction,
the photon interacts with the field of the nucleus and
disappears with the creation of a positive and negative
electron (e/e) pair (Fig. 9). This reaction is an example of
energy converting into mass. As the rest mass energy for
electron or positron is m0c2 0.511 MeV, the threshold for
pair production is 1.022 MeV. The total kinetic energy of
the electronpositron pair is
hn 1:022 E E
(13)
597
PHOTODISINTEGRATION
A photon with still higher energy may penetrate the
nucleus and knock out one of its constituents: a proton,
neutron, or alpha particle along with more gamma rays.
The incident photon is absorbed, and the nucleus is transformed into an unstable reaction product. The latter next
returns back to a stable state via radioactive decay of a
nuclear particle, for example, as in (g, p) and (g, n) reactions.
The threshold for the photodisintegration reaction is
essentially the binding energy of nucleons in the nucleus.
For low Z nuclei, this is above 10 MeV (except for Be: 2 MeV
and 2H: 1.5 MeV). For heavy nuclei, the nuclear binding
energy is about 7 MeV. Due to Coulomb repulsion, the
threshold for (g, p) is lower than that for the (g, n) reaction.
Beyond the threshold energy, the probability for photodisintegration increases rapidly with increasing incident
photon energy, reaches a maximum value, and then drops
with further increase in energy. This peak is referred to as
the nuclear giant resonance and is due to the electric dipole
absorption of the incident photon.
Compared with the other reactions described above, the
probability for photodisintegration is small and hence
does not contribute significantly to photon attenuation.
However, the interaction has great importance in shielding
considerations for radiotherapy room design.
(14)
r
r
r
r
r
Let us consider the plot of total mass attenuation coefficient as a function of photon energy for water and lead,
which, respectively, represent a low Z and high Z material
(Fig. 11). At low energies (10 keV), the photoelectric effect
is dominant. The attenuation coefficient displays Z3/E3
behavior in this region. Therefore, m is much higher for
lead (103 times) compared with water and decreases
rapidly with increasing photon energy.
As the photon energy exceeds electron binding energy
(100 keV and higher), the Compton effect takes over. As
the Compton interaction is independent of Z of medium,
lead and water have practically the same attenuation. As
the photon energy is further increased, the attenuation
coefficient decreases until the pair production becomes the
dominant mode of interaction (for photon energies higher
than 1 MeV).
In the pair production range, the attenuation coefficient
increases with energy as log E. Also, the likelihood of
interaction is higher in lead than in water because of
the Z dependence of pair production interaction. The above
behavior of various modes of interactions is summarized in
Table 2 for tissue-like material.
Another way to discuss the relative importance of various interactions is to look for them as regions of dominance
in the plot of hv versus Z (Fig. 12). The curves display
points in the hv and Z space for which the Compton effect
equals the photoelectric effect and pair production. The
Compton effect is most dominant between 1 and 5 MeV
(15)
Photoelectric
Compton
Pair Production
10 keV
25 keV
150 keV
4 MeV
24 MeV
100 MeV
95
50
0
0
0
0
5
50
100
95
50
16
0
0
0
5
50
84
598
Z of absorber
hv E tr E scat
16
E tr
m
hv
17
18
120
100
Photoelectric effect
dominant
mab
Pair production
dominant
E ab
m
hv
19
80
Table 3. Depth of Maximum Dose and Percent Depth Dose
at 10 cm Depth for Megavoltage Photon Beams
60
40
Compton effect
dominant
Photon Beam Energy
20
0
0.01
0.05 0.1
0.5 1
hv in MeV
10
50 100
1.25 MV (60Co)
4 MV
6 MV
10 MV
18 MV
25 MV
Depth of
Maximum Dose (cm)
0.4
1
1.6
2.5
3.5
5
Percent Depth
Dose at 10
cm depth (%)
58.7
63
66.7
73.2
79.2
84.5
X-RAYS, PRODUCTION OF
599
X-RAYS, PRODUCTION OF
BRUCE HORN
Kaiser Permanente
Los Angeles, California
INTRODUCTION
Soon after Wilhelm Roentgen discovered X rays in 1895,
scientists recognized their usefulness to visualize the
internal anatomy of humans. For a number of years, X-ray
tubes that radiologists used for this purpose were unreliable and produced low X-ray output. In 1913, William
Coolidge invented the forerunner of the modern X-ray
tube. Unlike earlier designs, this tube featured a heated
tungsten filament as the source of electrons and utilized a
high quality vacuum instead of the low gas pressure previously employed. The result was a reliable X-ray tube
whose X-ray output could be reproducibly controlled over a
wide range. Todays wide range of X-ray imaging techniques, from a simple chest radiograph to a multislice
computed tomogram, still depend on an X-ray tube to
produce X rays. Recent developments in X-ray tube design
include improved heat handling capability, increased
X-ray output, and reduced focal spot size.
PRODUCTION OF X RAYS
X rays, like radio waves, light, g rays, and other types of
electromagnetic radiation, are defined by their energy and
source. X rays are produced by two methods involving the
interaction of electrons with matter. In the first method, a
stream of electrons directed at a target is decelerated by
forces between the incident electrons and the atomic nuclei
of the target material. Since a deceleration implies that
kinetic energy is lost, one of the ways in which electrons
lose energy is by creating photons of electromagnetic
energy equal in energy to the kinetic loss. This process
is call bremsstrahlung, or braking radiation. The photons
produced by this interaction are commonly called X rays. If
a large number of electrons, all having the same initial
kinetic energy, interact with a target material, the resulting bremsstrahlung consists of photons, or X rays, with a
continuum of energies from zero to a maximum equal to the
initial electron kinetic energy. This range of energies is
called the X-ray spectrum. The shape of the spectrum
remains the same regardless of the kinetic energy of the
electrons. Although X rays are produced by this mechanism even if the target consists of a gas, the efficiency of
X-ray production by bremsstrahlung is directly proportional to the product of the atomic number (Z) of the target
600
X-RAYS, PRODUCTION OF
X-RAYS, PRODUCTION OF
601
602
X-RAYS, PRODUCTION OF
X-RAYS, PRODUCTION OF
603
604
X-RAYS, PRODUCTION OF
R 180M=puD
where R is the focal spot resolution in line pairs
per millimeter, u is the angle in degrees of a single wedge
of absorbing material, D is the diameter of the blur on the
film in millimeters, and M is the magnification factor of
the phantom image. For the typical star pattern phantom
with 28 wedges, this formula reduces to
R 28:65M=D
The diameter corresponding to the resolution of the
focal spot parallel with the anodecathode axis of the
X-ray tube (length) is the blur diameter that is perpendicular to this axis. Likewise, the diameter corresponding
to the focal spot resolution perpendicular to the anode
cathode axis (width) is the blur diameter that is parallel
with the anodecathode axis. The principal advantage of
the star pattern method of characterizing focal spots is its
X-RAYS, PRODUCTION OF
605
606
X-RAYS, PRODUCTION OF
taneous heat load during the short period of X-ray generation, there are limitations as to the total amount of
heat that the anode and tube housing can each store.
Basically, there are five parameters that describe the
heat dissipation characteristics of an X-ray tube: (1) focal
spot loading, (2) anode heat capacity, (3) anode cooling
rate, (4) housing heat capacity, and (5) housing cooling
rate.
These heat characteristics are described in terms of one
of two units, heat units or watt seconds. In the United
States, heat parameters are specified in heat units (HU).
The number of heat units generated by an X-ray exposure
is given by the following formula:
HU CVAt
where HU is the number of heat units, C is a waveform
factor, V is the tube potential in peak kilovolts, A is the
tube current in milliamperes, and t is the exposure
duration in seconds. The waveform factor corrects for
the differences in heating effect resulting from differences
in average power of different high voltage waveforms. For a
full-wave-rectified, single-phase waveform, the waveform
factor is 1.0. For a 12-pulse, three-phase waveform, the
waveform factor is 1.35. For example, an X-ray exposure of
100 kVp, 500 mA, 0.2 s using a single-phase generator
would result in 10,000 HU. The same technique using a
three-phase generator would result in 13,500 HU.
In Europe, heat parameters are expressed in
watt seconds (W s) or joules (J). The heat generated by
an X-ray exposure is given by the following formula:
E KVAt
where E is the heat in watt seconds or joules, K is a
waveform factor, V is the tube potential in peak kilovolts,
A is the tube current in milliamperes, and t is the exposure
duration in seconds. In this case, the waveform factor for a
full-wave-rectified, single-phase waveform is 0.74 and for a
12-pulse, three-phase waveform is 1.0. Therefore, the
quantity of heat represented by one heat unit is 26% less
than the quantity represented by 1 W s or joule. Using the
technique factors of the previous example (100 kVp, 500
mA, 0.2 s) results in 10,000 J of heat generated.
Focal Spot Loading
The heat handling characteristic of the X-ray tube focal
spot is expressed in terms of kilowatts for an exposure
duration of 0.1 s. The kilowatt loading of the focal spot
is equal to the product of the tube potential in peak kilovolts and the tube current in milliamperes divided by 1000.
It is the amount of power, or energy per second, deposited
as heat in the anode. Typical X-ray tube inserts used in
diagnostic radiology for high power procedures have focal
spot loading capabilities of 3040 kW for a small focus of
0.6 mm, and 100 kW for a large focus of 1.2 mm. The small
focus of such a tube could not be used for the example
technique of 100 kVp, 500 mA, because the focal spot
loading would be exceeded. This demonstrates the tradeoff between focal spot size and heat loading capability. A
focal spot of 0.3 mm may have a maximum heat loading of
as little as 9 kW. A tube insert with this rating could not be
X-RAYS, PRODUCTION OF
607
608
X-RAYS, PRODUCTION OF
Further Reading
X-RAYS, PRODUCTION OF
Coulam CM, Erickson JJ, Rollo FD, James AE Jr. The Physical
Basis of Medical Imaging. New York: Appleton-Century-Crofts;
1981.
Hendee W. Medical Radiation PhysicsRoentgenology, Nuclear
Medicine and Ultrasound, 2nd ed. Chicago (IL): Year Book
Medical Publishers; 1979.
International Electrotechnical Commission. X-Ray Tube Assemblies for Medical DiagnosisCharacteristics of Focal Spots.
Publ. No. 60336, Geneva: IEC, 2005.
National Electrical Manufacturers Association. Measurement of
Dimensions and Properties of Focal Spots of Diagnostic X-Ray
Tubes. Stand. Publ. No. XR 5-1992 (R1999), Washington (DC):
NEMA; 1999.
Ter-Pogossian MM. The Physical Aspects of Diagnostic Radiology.
New York: Harper & Row; 1969.
See also CODES
X-RAY EQUIPMENT
609
17. Purdy JA, Grant III W, Palta JR, Butler EB, Perez CA eds.
3-D Conformal and Intensity Modulated Radiation Therapy:
Physics & Clinical Applications: Advanced Medical Publishing, Inc., 2001.
18. Webb S, The Physics of Three-Dimensional Radiation Therapy: Conformal Radiotherapy, Radiosurgery and Treatment
Planning: Institute of Physics Publishing; 1993.
19. Hongstrom Kr, Paciotti MA, Smith AR, Coller M, Comparison
of static and dynamic treatment modes for the pion therapy
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20. Sisterson J ed. Particle Therapy Co-operative Group (PTCOG)
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1999.
23. Podgorsak FB, Podgorsak MB, Stereotactic Irradiation:
Chapter 16. In: Van Dyk J, ed., The Modern Technology of
Radiation Oncology, Medical Physics Publishing; 1999.
24. Washington CM, Leaver D, Principles and Practice of Radiation Therapy, Second Edition: Mosby; 2004.
25. Wang CC, ed. Clinical Radiation Oncology: Indications, Techniques, and Results Second Edition: Wiley-Liss; 2000.
26. Hall EJ, Radiobiology for the Radiologist, 4th Edition: J.B.
Lippincott; 1994.
27. Rossi HH, Zaider M, Microdosimetry and Its Applications:
Springer; 1996.
28. Greene D, Williams PC, Linear Acceleraators for Radiation
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29. Nias AHW, An Introduction to Radiobiology: John Wiley &
Sons, 1990.
30. Prasad KN, Handbook of Radiobiology, 2nd ed.: CRC Press;
1995.
31. Tsipenyuk YM, The Microtron: Development and Applications: Taylor & Francis; 2002.
32. Dobelbower RR, Abe M, Intraoperative Radiation Therapy:
CRC Press; 1989.
33. Chiu C, Fomytskyi M, Grigsby F, Raischel F, Downer MC,
Tajima T, Laser electron accelerators for radiation medicine:
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35. Shih CC, High energy electron radiotherapy in a magnetic
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36. Whitmire DP, D.L. Bernard DL, Peterson MD, Magnetic
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38. Litzenberg DW, Fraass BA, McShan DL, ODonnell TW,
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2002;29:24352437.
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FD, Magnetic confinement of electron and photon radio-
610
41.
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X-RAYS, PRODUCTION OF
therapy dose a Monte Carlo simulation with a non-uniform
longitudinal magnetic field. Med Phys 2005;32:3810
3818.
Maughan RL, Yudelev M, Neutron Therapy: Chapter 21. In:
Van Dyk J ed., The Modern Technology of Radiation Oncology. Medical Physics Publishing, 1999.
Forman JD, Yudelev M, Bolton S, Tekyi-Mensah S, Maughan
R, Fast neutron irradiation for prostate cancer, Cancer and
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51.
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55.
INDEX
Italic numbers preceding page references indicate the volume numbers. Page numbers followed by f denote figures; page numbers followed
by t denote tables.
612
INDEX
regenerative, 1:290
Allotropes, of carbon, 1:296298, 300301
Alloy refining, of nickeltitanium shape
memory alloys, 1:5
Alloys
as prosthetic restorative materials,
1:325326
shape memory, 1:112
Alpha Eta Mu Beta, 4:316317
Alpha waves, EEG, 3:66
Alternate image plane display, in
computed tomography, 2:239
Alternating current (AC), in
cardiopulmonary resuscitation,
2:3637. See also AC entries
Alternating vision contact lenses, 2:327
Alumina. See also Aluminum oxide
in dental implants, 1:328329
in orthopedic prostheses, 1:317318
reticulated, 1:355356, 357, 358, 359,
360
Aluminum oxide, as biomaterial, 1:108, 272
Aluminumtitanium catalysts, 1:106
Alveolar air/ventilation, CPR and, 2:40
Alveolar minute ventilation, 6:104105
Alveolar ventilation, 2:42
Alza Macroflux technology, 2:503
Alzheimers disease (AD)
cognitive training for persons with,
6:7374
multidimensional study of, 1:396397
Amalgam, dental, 1:322323
Ambient light, pulse oximetry and, 5:212
Ambient vibration, power generation with,
4:431433
Ambulatory blood glucose monitoring,
1:1617
Ambulatory blood pressure monitoring,
1:1316, 489
basic techniques of, 1:14
clinical concepts related to, 1:1415
indications of, 1:15
limitations of, 1:16
Ambulatory blood pressure profile,
interpretation of, 1:15
Ambulatory event monitoring, 1:134
Ambulatory glucose monitoring,
significance of, 1:17. See also
Ambulatory blood glucose monitoring
Ambulatory monitoring, 1:1218
with a Holter device, 1:1213
Ambulatory pump, drug infusion systems,
2:501502
Ambulatory tonometer, 6:407
American Academy of Environmental
Engineers, 4:317
American Academy of Orthopaedic
Surgeons, 4:317
American Academy of Orthotists and
Prosthetists, 4:317
American Academy of Sleep Medicine
guidelines, 6:212
American Association of Engineering
Societies, 4:317
American Association of Physicists in
Medicine, 4:317
American Chemical Society, 4:317
INDEX
American College of Nuclear Physicians,
4:317
American College of Physicians, 4:317
American College of Radiology (ACR),
4:317378; 6:560
American College of Surgeons, 4:318
American Congress of Rehabilitation
Medicine, 4:318
American Heart Association (AHA), 2:48,
49, 52
American Institute for Medical and
Biological Engineering (AIMBE),
4:314316, 317
American Institute of Biological Sciences,
4:318
American Institute of Chemical Engineers,
4:318
American Institute of Physics, 4:318
American Institute of Ultrasound in
Medicine, 4:318
American Medical Informatics Association,
4:318
American National Standards Institute
(ANSI), 1:158
anesthesia machine standards of, 1:31
audiometry standards by, 1:92, 99
American Physical Therapy Association
(APTA), 1:168
American Society for Artificial Internal
Organs, 4:318
American Society for Engineering
Education, 4:318
American Society for Healthcare
Engineering of the American Hospital
Association, 4:318
American Society for Laser Medicine and
Surgery, 4:319
American Society for Testing and
Materials (ASTM) designations, 1:104,
105
American Society of Agricultural and
Biological Engineers, 4:319
American Society of Civil Engineers, 4:319
American Society of Clinical Pathologists
(ASCP), 1:455
American Society of Heating,
Refrigerating, and Air-Conditioning
Engineers, Inc., 4:319
American Society of Mechanical
Engineers, 4:319
American Society of Neuroradiology, 4:319
American Society of Safety Engineers,
4:319
American Thoracic Society (ATS)
standards, 5:369
Amino acids, boron-containing, 1:573574
Amnesia, electroconvulsive therapy and,
3:56
Amnioexchange, 4:176178
Amniopatch, 4:178
Amplification, in linear variable
differential transformers, 4:253
Amplifier characteristics, EMG, 3:106107
Amplifierrecorder, in anorectal
manometry, 1:63
Amplifiers
ECG, 1:175
EEG, 1:172
electrodermal biofeedback, 1:173
EMG, 1:169
heart rate, 1:175
respiration, 1:174175
temperature, 1:170
for use with strain gages, 6:286
Amplitude and frequency analysis, in
arrhythmia analysis, 1:76
Amplitude distribution, in EEG analysis,
3:69
Amplitude-integrated EEG (aEEG)
monitor, 5:36
Amplitude variability analysis (AVA), for
automatic external defibrillators,
1:80
Amsler grid, 6:529
Amundson porous electrode, 1:153154
Anal pressure, resting, 1:6364
Anal sensation, assessment of, 1:65
Analgesia, 3:25. See also Electroanalgesia
Analog display feedback schedule, 1:176
Analog-to-digital conversion (ADC), 5:112
Analogue data, 1:396
Analogue recorders, 6:4951, 5559
Analysis of variance (ANOVA), 1:224
Analyte 2000TM fiber-optic
fluoroimmunoassay system, 4:378
Analytical cytometry, of whole blood, 1:460
Analytical methods, automated, 1:1828
Analytical reconstruction techniques,
2:247
Analytic X-ray units, regulations related
to, 2:175
Analyzers. See also Oxygen analyzers
automated, 1:19
chemistry, 1:1923
critical care, 1:2122
general chemistry, 1:2021
immunoassay, 1:21
Anaphylotoxins, 1:281
Anatomical joint models, 4:216
Anatomy, articular, 4:199201
Ancient DNA, 5:384385
Anderson loop circuit, 6:285286
Anemometry, thermal, 3:329330
Anesthesia
automatic feedback control for, 1:49
brain monitoring in, 4:558560
computer information technology in,
1:4447
computers in, 1:4251
diagnosis and decision assistance for,
1:50
electrical, 3:2730
electroconvulsive therapy and, 3:57
electropharmaceutical, 3:32
future of computer technology in,
1:5051
as a procedure, 4:556
as a process, 4:556557
system identification and adaptive
control for, 1:4950
telemedicine in, 1:47
typical process of delivering, 1:29
Anesthesia control, computer-aided,
1:4750
613
614
INDEX
INDEX
misinterpreted, 6:577
Artificial blood, 1:511523
hemoglobin solutions, 1:516
perfluorochemical emulsions, 1:513515
Artificial eye, 1:453
Artificial heart, 3:449459
clinical need for, 3:449
design considerations for, 3:450451
electric, 3:457458
future directions of research on,
3:458
pneumatic, 3:457
Artificial hip joint bearing surfaces,
tribology of, 3:517518
Artificial hip joints, 3:514525
applications of, 3:518521
bearing surfaces of, 3:515516
future developments in, 3:521522
historical development of, 3:514515
nomenclature related to, 3:522523
tribological and biological methodology
for, 3:516518
Artificial intelligence, in exercise training,
1:393
Artificial intervertebral disk, 3:587588
Artificial larynx, 4:230231
Artificial neural networks (ANN), 1:497
Artificial pancreas, 5:224234
clinical studies of, 5:230, 231t
components of, 5:226
cost of, 5:230
historical background of, 5:225
indications for, 5:230
outlook for, 5:230
physiological considerations related to,
5:225226
prototypes of, 5:227230
types of, 5:221
Artisan lenses, optical quality of,
4:237238
Aseptic loosening, 1:314
As low as reasonably achievable (ALARA)
principle, 6:472, 573
Aspiration, through micropipettes, 1:507
Assessment, of communication disorders,
2:214217
Assisted circulation, 3:459461
Assisted reproductive technologies,
microfluidic systems as, 4:394
Assistive devices
benefits and limitations of, 2:223224
for communication disorders, 2:221224
hearing, 2:222223
language, 2:221222
new directions in, 2:225
Assistive technologies. See also Mandated
web accessibility
for the blind and visually impaired,
1:443455
future possibilities for, 1:453454
GPS navigational aids, 1:451453
independent living aids, 1:447448
indoor navigational aids, 1:453
intelligent electronic travel aids,
1:450451
low vision reading aids, 1:444445
mobility aids, 1:448, 449t
615
616
INDEX
INDEX
Binary display feedback schedule,
1:176
Binary leaf collimator, 6:397
Binding energy, X-ray photon spectroscopy
and, 1:349
Binomial distribution, 6:244245
Binomial variables, binomial test for,
6:249250
Bioactive ceramic materials, 1:272
use in medical devices, 1:314
Bioactive fixation, 1:285, 289
Bioactive glass foams, solgel derived,
1:292293
Bioactive glasses, 1:284, 285
bioactivity mechanism of, 1:285286
melt-derived, 1:287
porous melt-derived, 1:291292
solgel-derived, 1:287289
Bioactive materials, 1:104, 284
Class A and B, 1:289
genetic control by, 1:290
Bioactive photoresist, 1:411
Bioactive skin substitutes, role of, 6:172.
See also Skin substitutes
Bioactivity, of glasses, 1:286287
Bioactivity test, of biomaterials, 1:360362
Bioartificial livers, 4:393
Bio-barcode technology, nanoparticlebased, 4:379380
Biobrane, as a skin substitute, 6:175
Bioburden, 6:274
Bioceramics, 1:283296, 355
challenge for, 1:284285
as medical devices, 1:284
nearly inert, 1:284
in regenerative medicine, 1:290
resorbable, 1:285
Bioceramic scaffolds, 1:374375
types of, 1:291
Biochemical measurement, neonatal,
4:590591
Biochemical precursors, 1:574575
Biochemical probes, with DNA specificity,
2:391t
Biocompatibility, 1:8, 130
of biomaterials, 1:281282
of carbon biomaterials, 1:301
of engineered tissue, 3:201
of implants, 1:256
of materials, 1:104120
of nanoporous membranes, 2:451
in orthopedic devices, 5:191192
surface modification of scaffolds for,
1:379
Biocompatibility assessment, of polymeric
biomaterials, 1:341
Biocomposites, 1:289
Biodegradable polymeric drug delivery
systems, 2:504
Biodegradable polyurethane, in tissue
engineering, 1:373374
Biodegradable synthetic polymers,
1:339340
Bioeffects, ultrasound-related, 6:471473
Bioelectric potential (BEP), 1:559560
Bioelectrodes, 1:120166
designing, 1:120121, 137158
617
618
INDEX
Biomaterials (Continued)
chemical bonding of bone to, 1:109110
classification of, 1:269
common uses for, 1:269t
composite, 1:108
corrosion and wear of, 1:308322
covalent modification of, 6:388389
defined, 1:267
for dentistry, 1:322329
factors in failure of, 1:278281
future directions for, 1:282
government regulation of, 1:268270
healthcare treatments requiring, 1:270t
history of, 1:267268
journals related to, 1:269t
market size and applications related to,
1:268
normal local tissue response to,
1:108110
polymeric, 1:329342
in restorative dentistry, 1:313
standards for, 1:281282
structural properties of, 1:362364
for tissue engineering, 1:367375;
6:383387
types of, 1:270278
in vascular graft prostheses, 6:498
Biomaterials Access Assurance Act, 4:315
Biomaterial scaffolds, for engineering
articular cartilage and meniscus, 2:74.
See also Biologic scaffold materials
Biomaterials testing, 1:354365
materials and methods related to,
1:355357
Biomaterial surfaces, 1:341, 342354
adsorption of proteins at, 1:344345
ambient techniques for characterizing,
1:351352
analysis of, 1:348351
cell behavior at, 1:345
modification of, 1:345348
properties of, 1:343345
Biomaterialtissue interface, degeneration
of, 1:110111
Biomechanical models, of mastication,
6:417424
Biomechanical research, strain gages in,
6:287
Biomechanics
of diabetic skin ulceration, 6:206207
of engineered tissue, 3:200201
of exercise fitness, 1:384403
as a hospital problem, 6:114
occipitalatlantoaxial complex,
3:554555
of scoliosis, 6:122137
of scoliosis progression during growth,
6:129
skin, 6:202208
of spine stabilization procedures,
3:568591
Biomedical applications
capacitive microsensors for, 2:112
of fluorescence measurements,
3:345346
of microfluidics, 4:426427
of polymers, 1:333341
Bioreactors
in bone tissue engineering, 6:391
in cardiovascular tissue engineering,
6:393, 394
design of, 6:388
in tissue engineering, 6:387388
Bioreactor technology, engineered tissue
and, 3:200
Bioresist, 1:411
Bioresorbable ceramics, 1:272
Biosensors, 4:376
Biosensor techniques, impedimetric, 4:143
Biosignal monitoring electrodes
external, 1:137139
implanted and external, 1:130
standards for, 1:158160
Biostator artificial pancreas, 5:227
Biosurface engineering, 1:409417
patterning methods in, 1:409414
Biosusceptometers, 1:238
Biosusceptometry, 1:231
biomagnetic measurements and, 1:247
Biotelemetry, 1:417429
Biotelemetry systems, 1:418423
diagnostic applications of, 1:423
interface electronics in, 1:418
packaging and encapsulation of,
1:422423
power sources for, 1:422
rehabilitative, 1:424427
therapeutic applications for, 1:424
transducers in, 1:418
wireless communication in, 1:418422
Bioterrorism, monoclonal antibodies and,
4:607
Biotribology, 1:314
Biphasic theory, 2:69
Biphasic waveforms, 1:128
Bipolar electrodes, 1:151
configuration of, 1:198199; 3:106
Bipolar forceps electrode field, in
electrosurgery, 3:175176
Bipolar lead systems, in exercise stress
testing, 3:248
Bipolar recording configuration, 3:114115
Bipolar recordings, with EEG biofeedback
instrumentation, 1:171
Bipolar umbilical cord occlusion, 4:179
Birdcage electrode design, 1:154
Bispectral index (BIS), 2:506
neurological monitor, 5:3839
Bispectral Index Score (BIS), 4:560
Bispectrum analysis, EEG, 3:71
Bisphenol A polycarbonate, 1:338
Bisping transvenous screw-in electrode,
1:152
Bite block, 5:590
Black body, 6:361
Bladder, overactive, 1:441
Bladder applications, for porous
biomaterials, 5:403
Bladder dysfunction, neurostimulation of,
1:429443
Bladder dysfunction hardware, future of,
1:441442
Bladder function, visceral neural signals in
control of, 3:128129
INDEX
Bladder stimulation, 1:430
Bleeding. See also Blood
lower GI, 3:391392
upper GI, 3:385390
Blindness, 6:532533
defined, 1:443444
prevalence of, 1:444t
Blind persons
assistive technology for, 1:443455
readings aids for, 1:445447
Blind source separation, 1:242
Blogs, in office automation systems, 5:156
Blood. See also Artificial blood; Bleeding;
Hemo-entries
banked, 1:512513
mass and thermal transport via, 1:188
measurement of oxygen in, 6:522524
measurement of pH and carbon dioxide
in, 6:525526
thermal properties of, 2:28
Blood-cell cancers, 4:606
Blood cell counters, 2:8190. See also
Complete blood cell count
automated, 2:8889
electronic, 2:8485
history and principles for, 2:8286
rationale for cell count, 2:82
types of, 2:8286
Blood cell counting, impedance
plethysmography and, 4:130
Blood cells. See also Red blood cell entries;
White blood cell entries
characteristics of, 2:81t
measuring rheological properties of,
1:506507
nature of, 2:8182
biomaterial failure and, 1:280
Blood collection, tube guide for, 1:457t
Blood collection/processing, 1:455465
safety in, 1:456
specimen storage in, 1:460t
standard changes in, 1:455456
Blood collection system/equipment,
1:457458
Blood compatible glassy carbons, 1:301
Blood component home health care devices,
3:531532
Blood contact, biomaterial failure related
to, 1:280
Blood flow. See also Blood rheology;
Cutaneous blood flow
character of, 3:2122
cooling and, 3:466
effective, 2:1617
heat transfer and, 1:191
maldistribution of, 6:164
pulmonary, 2:1618
smooth muscles and, 1:190
systemic, 2:1618
thermotherapy and, 3:464465
Blood flow conductivity, based on
erythrocyte orientation, 1:208
Blood gas analysis
considerations in, 6:526527
impact of, 2:113
Blood gas analysis apparatus, 2:112
three-function, 2:113
619
620
INDEX
INDEX
Bucky balls, 1:298, 305
Bucky tray, 6:569
Bulk micromachining technologies, 2:3, 4f
Bulletins, Nuclear Regulatory
Commission, 2:171
Burger, Rudolph, 1:138
Burn injury, 6:170172
Burns, 1:192
bioactive skin substitutes for, 6:169179
deep second degree (deep partial
thickness), 6:170171
etiology and prognosis relative to depth
of, 6:171t
laser Doppler flowmetry for, 2:382
mean survival rate after, 6:171t
scars and pain in, 6:171172
size and depth of, 6:170
superficial second degree, 6:170
third degree (full thickness), 6:171
Bursae, 4:199201
Bursitis, tissue regeneration and, 1:109
Burst and analyzing methods. See EEG
burst and analyzing methods
Burst detection
reasons for, 3:7374
methods of, 3:7980
Burst-episodes, analyzing, 3:74
Bursting, signal-power changes during,
3:7479
Bursts, mechanisms of, 3:7273
ButlerVolmer equation, 1:124, 129
Cabling, in electroneurography, 3:116
Cadaver models, osteoligamentous, 3:573
Cadaver skin, as a skin substitute,
6:173174
CADe schemes, 2:298
Cadmium telluridide (CdTe) detectors,
5:518
CAD schemes. See also Computer-assisted
detection/diagnosis (CAD)
evaluation of, 2:298302
scoring criteria for, 2:299300
CAD server, 2:303
CADx schemes, 2:297298
Cages, in spine stabilization, 3:571572
Calcineurin inhibitors, 4:275
Calcium alginate scaffolds, 1:367
Calcium ceramics, resorbable, 1:260262
Calcium concentration, in bioactivity
testing, 1:360361, 364365
Calcium-containing materials, bone
bonding to, 1:109110
Calcium ions, bioactive glasses and, 1:286
Calcium oxides, as biomaterials, 1:273
Calcium phosphate materials, 1:261262
Calcium phosphates, as biomaterials,
1:108
Calcium scoring, computed tomography
and, 2:243
Calcium sulfate materials, 1:260261
Calendars, in office automation systems,
5:154
Calibration
audiometric, 1:93
in effective thermal property
measurements, 1:196
621
622
INDEX
guiding, 2:349
with heating elements, 2:27, 28
intravascular optical blood gas,
5:168169
in microsurgery, 4:532
mixed-venous fiber optic, 5:165166
proximal, 4:910
pulmonary artery, 2:2930; 4:572573
SwanGanz, 2:26, 30
for thermal dilution measurement, 2:24f
umbilical artery, 4:594595
umbilical artery/vein, 4:590
umbilical venous, 4:595
volume conductance, 1:206207
water-perfused, 1:62
Catheter-tip transducer systems, 4:579
Cathode, 1:465466
CEDIA enzyme immunoassay, 1:21
Cell adhesion, protein-mediated,
5:396397
Cell-based drug screening, impedance
spectroscopy as a tranducer in,
4:140142
Cell behavior
growth factors necessary for modulating,
2:74
at surfaces, 1:345
Cell counters, blood, 2:8190
Cell culture, in medical microbiology, 4:375
Cell Culture Analogs (CCAs), micro, 4:393
Cell elasticity measurements, 4:512
Cell imaging, impedance plethysmography
and, 4:130131
Cell manipulation, nanoparticles in, 5:67
Cell-mediated immune response, 1:113
Cell metabolism
cooling and, 3:466
temperature and, 3:464
Cell patterning, potential applications for,
1:413414
Cell Preparation Tube (CPT), separation of
peripheral blood mononuclear cells
using, 1:462464
Cells
in automated cytology, 2:389390
in biosurface engineering, 1:409
controlling attachment, morphology, and
differentiation of, 1:414
instrumentation for defining,
enumerating, and isolating, 4:603604
monitoring attachment and spreading
in, 4:139140
in tissue engineering, 1:366
tissue regeneration and, 1:108109
Cell seeding, in tissue engineering, 6:387
Cell separation, in microbioreactors,
4:390391
Cell separation/purification, nanoparticles
in, 5:5
Cell sorting, 2:397399
Cell sources
in bone tissue engineering, 6:390
in cardiovascular tissue engineering,
6:392, 393, 394
Cell-to-cell interactions, in engineered
tissue, 3:200
Cell types, in engineered tissue, 3:192193
INDEX
Cellular cardiomyoplasty (CCM), 6:393
Cellular imaging, 2:90101
fluorescence and, 2:91
Raman and CARS microscopy, 2:9899
Cellular parameter measurement
in automated cytology, 2:392400
devices used in, 2:397400
Cellular patterning techniques, 1:409414
Cellular processes, in engineered tissue,
3:190194
Cellular solid porous biomaterial
fabrication, 5:400
Cellular thermal damage, 4:48
Celsius temperature scale, 6:312
Cemented prosthesis fixation, 5:194
Cementless prosthesis fixation, 5:194195
Cements
calcium phosphate, 1:262
dental, 1:324325
Censoring, 6:262263
Centigrade temperature scale, 6:312
Central auditory processing disorder, 2:211
Central auditory system, 1:95
Central limit theorem, 5:534
Central nervous system applications, for
porous biomaterials, 5:404
Centrifugal flow ventricular assist device,
3:454455
Centrifuges, separation of peripheral blood
mononuclear cells using, 1:462
Cerabone, 1:287
Ceramic materials, use in medical devices,
1:313314
Ceramic-on-ceramic hip joints, 3:521
Ceramic-on-metal hip joint bearing,
3:521522
Ceramics
as biomaterials, 1:107108, 272273
as prosthetic restorative materials,
1:326327
resorbable calcium, 1:260262
Cerebral autoregulation, in whole-body
models, 5:306307
Cerebral cortex, organization of, 3:63
Cerebral function monitor, 5:3536
Cerebral injury, EEG and, 3:67
Cerebral metabolism, EEG and, 3:67
Cerebral State Monitor (CSM), 4:562
Cerebral systems modeling, 5:313316
Cerebral topography, EEG and, 3:67
Cerebrospinal fluid (CSF), 4:576578
circulation of, 4:12
pulsations of, 4:2
resistance to reabsorption of,
4:35
Cerebrospinal fluid drainage valves,
4:1012
Cerebrovascular disease, 2:5153
vascular graft prostheses and, 6:493
Cervical cap, 2:340341
Cervical dilatation, continuous monitoring
of, 3:300
Cervical region, surgical procedures and,
3:566568
Cervical spine, anatomy of, 3:547551
Cervical spine region, degeneration
trauma in, 3:562564
623
624
INDEX
INDEX
Combined gas law, 2:14
Combined magnetic field (CMF), 1:567
Committed effective dose, 5:505
Committed equivalent dose, 5:505
Committees, in a total hospital safety
program, 6:115
Common peroneal nerve stimulation,
1:430
Communication devices, 2:202210. See
also Augmentative and alternative
communication (AAC) systems
Communication disorders
assessment of, 2:214217
assistive devices for, 2:221224
computer administrationinformation
processing and, 2:211213
computer applications for, 2:210229
future directions of, 2:224225
intervention in, 2:217221
normal function analysis and, 2:213214
Communication, in a total hospital safety
program, 6:115
Communication networks, in
teleradiology, 6:305306
Communicative competence, training for,
2:208209
Community CPR, mechanisms for,
2:4850
Compact bone
as a composite material, 1:532533
electrical properties of, 1:536
mechanical properties of, 1:523534
Comparative genomics, 1:222223
Comparative protein modeling techniques,
1:221
Compartment modeling, 6:431434
three or more compartments in, 6:433
Compartment syndrome, hyperbaric
medicine and, 4:2526
Compensating filter, 5:597
Complement system, implants and, 1:112
Complete blood count (CBC), 1:459, 460;
2:8688
Complex formation
in colorimetry, 2:192
methods used to detect, 2:454
Complex impedance plot, 1:124
Complexity-based neurological monitor,
5:39
Complexity measurements, in separating
ventricular fibrillation from
tachycardia, 1:79
Complex systems, niosomes in, 2:475
Compliance, in anorectal manometry, 1:67
Compliance issues, in continuous positive
airway pressure, 2:335336
Composite biomaterials, 1:108. See also
Composites
Composite resins. See Resin-based
composites
Composites. See also Composite
biomaterials
bioactive, 1:289
resin-based, 6:9399
resorbable, 1:262264
Compound biological effectiveness (CBE),
1:572
625
626
INDEX
INDEX
Contamination, of polymerase chain
reaction, 5:381382
Content-Addressed Storage (CAS), 5:350
Content-based image retrieval (CBIR),
4:359
Contingent negative variation (CNV),
3:237
Continuous BP monitoring, 5:235237.
See also Blood pressure entries
Continuous flow ventricular assist devices,
3:454
Continuous intraarterial pO2
measurement, 5:212213
Continuous intravascular blood gas
monitoring (CIBM), 1:474476
clinical uses for, 1:475
limitations and complications of, 1:475
Continuous intravascular neonatal blood
gas/biochemical sensors, 4:591592
Continuous phase composite (CPC), 1:263
Continuous positive airway pressure
(CPAP), 1:38; 2:329336; 6:508,
511512
advantages of, 2:336
comfort/compliance issues in, 2:335336
definitions related to, 2:330t
indications for use of, 2:334335
leak circuit modification in, 2:329330
monitoring/titration issues related to,
2:332334
in obstructive sleep apnea/hypopnea
syndrome (OSAHS), 2:329332
variations in, 2:330332
Continuous variables
parametrical hypothesis testing on,
6:251
probability density function for, 6:244
Continuous wave Doppler (CW), 3:1
Continuous wave Doppler ultrasound (US),
in peripheral vascular noninvasive
measurements, 5:241242
Contraception, research and development
related to, 2:347348
Contraceptive devices, 2:336349
bilateral tubal sterilization, 2:346347
cervical cap, 2:340341
efficacy of, 2:337338
female condom, 2:339340
informed consent concerning, 2:338
intrauterine devices, 2:345346
Leas shield, 2:341
male condom, 2:338339
transdermal contraceptive patch,
2:343344
vaginal spermicides, 2:340
Contraceptive diaphragm, 2:342343
Contraceptive implants, 2:344345
Contraceptive patch, transdermal,
2:343344
Contraceptive sponge, 2:341342
Contraceptive vaginal ring, 2:344
Contractility, of the heart, 4:567
Contraction, of muscles, 1:391392
Contrast, in computed tomography,
2:252253
Contrast bath hydrotherapy, 3:464
Contrast dye echocardiography, 2:38
627
628
INDEX
Cross-linking (Continued)
in UHMWPE, 1:334335
of ultrahigh molecular weight
polyethylene, 1:316317
Cross-spectral analysis, EEG, 3:7071
Crosstalk minimization, in ocular motor
recording, 5:146147
Crowns, dental, 1:325329
Crush injury, hyperbaric medicine and,
4:2526
Cryoablation (cryotherapy, cryosurgery),
6:366367, 371, 374, 376
Cryobiology, 1:188189, 192
Cryogenics, 1:236
Cryopreservation, 1:192
of engineered tissue, 3:201202
Cryoprotective agents (CPAs), 1:192
Cryosurgery, 2:360378
apparatus associated with, 2:363366
clinical uses for, 2:372376
comparison with other treatment
methods, 2:376
effect on tissue, 2:362363
future directions in, 2:376377
historical developments in, 2:361362
monitoring technique for, 2:368372
techniques for, 2:366368
Cryosurgical device, 2:365f
Cryotherapy, 3:474475
history of, 3:463464
Crystalline carbons, 1:296297, 298f
Crystalline polymers, 1:314
Crystallinity, polymer degradation via,
1:257258
Crystal structures, of nickeltitanium
shape memory alloys, 1:34
CsCl-type structure, for NiTi shape
memory alloy, 1:34
CT image slice thickness, 6:577
CT imaging system, Hi-ART II, 6:399401
CT perfusion imaging, 2:242243
CT reconstruction techniques, 2:246250
CT scan. See also Computed tomography
(CT)
axial, 2:237238
dynamic, 2:238
helical, 2:238
CT scanners
components of, 2:234237
primary technical parameters of, 2:269t
CT simulators, 5:527, 586587
Cuff electrodes, 1:157
Cuff oscillometry, 1:14
Cultured epithelial autograft, 6:190191
Curable prosthetic intervertebral nucleus
(PIN), in situ, 3:586
Current. See also Currents
at electrode-electrolyte interface,
1:126127
endogenic ionic, 1:199
high frequency, 3:157
Currentclamp technique, 3:142143
Current density, distribution under an
electrode, 1:144146, 148
Current density hotspots, 1:121
Currents. See also Current
brain, 1:238239
extracellular, 3:110111
Currents of linearity, 1:128129
Current sources, in temperature
measurement electronics, 6:327
Cushion form hip joint bearings, 3:522
Cutaneous afferent feedback
for correction of dropfoot, 3:126127
for restoration of hand grasp, 3:127
Cutaneous blood flow, Doppler
measurement of, 2:378384. See also
Laser Doppler flowmetry
Cutting processes, electrosurgical,
3:169170
CW Doppler assessment, 5:243
Cyanide poisoning, hyperbaric medicine
and, 4:27
Cyanine dyes, 4:468
CyberKnife robotic radiosurgery unit,
5:578
Cycle length (CL) values, in rate-based
arrhythmia detection, 1:71
Cyclodextrins (CDs), 2:452454
as drug delivery systems, 2:454460
elimination of, 2:454
toxicological profile of, 2:454
Cyclotron radionuclide production, 5:92
Cyclotrons, regulations related to, 2:175
Cylindrical model, of a vessel segment,
1:199200
Cylindrical tubes, blood rheology studies
in, 1:504505
CYPHER stent, 1:278
Cystic fibrosis sweat test, 2:384388. See
also Quantitative GibsonCooke
Pilocarpine Iontophoresis Sweat Test
(GCST/QPIT)
history of, 2:385
state of the art of, 2:386387
Cystoscopy, 3:183
Cytochemical probes, 2:390392
Cytochemistry, 2:411
Cytokine-release system, for tissue
engineering, 1:375377
Cytokines, in whole blood, 1:460
Cytology. See Automated cytology; Cell
entries
Cytoplasmic granularity, 2:411
Dacron, 1:338
in cardiovascular applications, 1:276
vascular graft prostheses, 6:494
Daily activity and sleep home health care
devices, 3:534
Daltons law, 1:465; 2:14; 4:19
Danazol, 6:154
Danmeter AEP Monitor/2, 4:561562
Data, in the biomedical laboratory,
2:308310
Data acquisition
in automated cytology, 2:400403
in single photon emission computed
tomography, 2:278280
Data acquisition system
in CT scanners, 2:235237
in neurological monitors, 5:34
Data analysis
for DNA microarrays, 4:366
INDEX
automatic external, 1:7980; 2:5657
external, 2:406407
implantable, 2:407409
implantable cardioverter, 1:6970,
7179
publicly available, 2:49
standards for, 1:160161
Deformity, orthotics and, 6:80
Degenerate polymerase chain reaction,
5:384
Degenerationtrauma, spinal motion
changes due to, 3:562566
Degenerative bone disease, implants for,
6:234
Degenerative disk disease, 6:232233
implants for, 6:234237
Degradable polymeric biomaterials, 1:279
Degradation
biomaterial failure from, 1:279
of biomaterials, 1:308309
of polymers, 1:314
Degradation byproducts, of porous
biomaterials, 5:398399
Degree of polymerization (DP), 1:331
Degrees of freedom (DOF), 6:246, 255256
of joints, 4:205207
Dehydration rehydration vesicles (DRVs),
2:469
Delivery catheter
for Guidant Galileo IVB system,
1:606607
in IVB devices, 1:603
for Novoste BetaCath, 1:604
Delrin, 1:338
Delta waves, EEG, 3:66
Dementia, 2:211
cognitive training for persons w1th,
6:7374
Demineralized bone particles, in tissue
engineering, 1:374375
Demodulation, in linear variable
differential transformers, 4:253254
Density, of bone, 1:529530
Dental amalgam, 1:322323
Dental arches, 6:412f
Dental bridges, 6:425
Dental ceramic materials, classification of,
1:326t
Dental electrosurgery, 3:160
Dental fillings, 1:322325
Dental implants, 1:327329; 6:426427
Dental research, strain gages in, 6:287288
Dental restorative filling materials, resinbased composite, 6:9399
Dentin, 1:324
Dentistry
adhesives, cements, and liners in,
1:324325
biomaterials for, 1:322329
prosthetic restorative materials in,
1:325329
Dentition, 6:411414
Denture base materials, 1:327
Denture materials, 1:325329
Dentures
fixed partial, 6:425
removable, 6:425426
Deoxyhemoglobin, 2:40
Department of Defense (DOD), 2:155
Department of Energy (DOE), 2:155
Department of Transportation (DOT),
2:155
Departments, in a total hospital safety
program, 6:116
Depolarization width, in feature-based
arrhtyhmia algorithms, 1:76
Depth monitors, in anesthesia, 1:44
Derivative area method (DAM), 1:7475
Derivatization, 2:193
Derjaguin approximation, 1:351
Dermal drug delivery, cyclodextrins in,
2:455456
Dermal regeneration template (DRT),
6:193196
Dermal replacement, living, 6:191
Dermis, 1:131
morphology and function of, 6:188189
properties of, 6:169170
Dermis components, involved in healing
and skin substitutes, 6:172t
Descriptive statistics, 6:241243
Desflurane vaporizers, anesthesia
machine, 1:36
Desktop publishing, in office automation
systems, 5:154
Desorption, of polymers, 1:314
Detection system, polymerase chain
reaction as, 5:384. See also Computerassisted detection/diagnosis (CAD)
Detective quantum efficiency (DQE), 5:338;
6:556
Detector arrays, 5:482
Detector calibration, in X-ray therapy
equipment, 6:585586
Detectors, for three-dimensional
dosimetry, 5:482484
Detrusor stimulation, 1:431, 432
Developmental bone deformities, spinal,
6:231232
Developmental language disorders, 2:211
Developmental spine deformities, implants
for, 6:234
Deviant sexual arousal, 6:159161
assessment of, 6:159161
Device calibration, in microdialysis
sampling, 4:405409
Devicedevice interaction, as a hospital
problem, 6:113
Device operators, as a hospital problem,
6:112
Dewars, 1:236, 237
Diabetes, acute coronary events and, 2:50.
See also Glucose sensors
Diabetes mellitus, laser Doppler flowmetry
for, 2:382
Diabetic skin ulceration, biomechanics of,
6:206207
Diagnosis. See also Computer-assisted
detection/ diagnosis (CAD); Diagnostic
entries
fluorescence techniques in, 6:480481
of implant-related infection, 1:116
uses of ultraviolet radiation in,
6:480482
629
630
INDEX
INDEX
in three-dimensional conformal
radiotherapy, 6:34
Dose calculation functions, relationships
between, 2:130131
Dose conversion, between materials,
5:471
Dose display, in radiation dose planning,
5:462463
Dose equivalent, 5:467
Dose fractionation, effect of, 2:260
Dose functions, cobalt-60 unit, 2:130131
Dose gradient, 5:582
Dose homogeneity, 5:583
Dose modifying devices, 5:594599
Dose optimization, in high-dosage-rate
brachytherapy, 1:598
Dose prescription, in three-dimensional
conformal radiotherapy, 6:33
Dosevolume histogram analysis, 5:547
Dosevolume histograms (DVHs), 5:462
463, 580581
Dosimeter characteristics, required for
quality assurance, 5:482
Dosimeters
calibration of, 5:474476
chemical, 5:474
Fricke, 5:473
personnel, 5:517t
reference or secondary, 5:471474
thermoluminescent, 5:473474
X-ray, 6:585
Dosimetric formalism, 5:421, 423
Dosimetry. See also Radiation dosimetry
BetaCath IVB system, 1:605
in boron neutron capture therapy,
1:572573
Checkmate IVB system, 1:604
experimental, 1:614615
gel, 5:484488
in the Guidant Galileo IVB system,
1:608609
of 131I-MIBG therapy, 5:569570
internal, 5:493
in intraoperative radiotherapy, 6:23
in new drug development, 5:571572
in prostate seed implants, 5:420424
in radioimmunotherapy, 5:570571
for radionuclide therapy, 5:567571
radiopharmaceutical, 5:565574
theoretical, 1:613614
Dosimetry calibration, in X-ray therapy
equipment, 6:584586
Dosimetry systems, quality assurance
procedures requiring, 5:481482
Double blind clinical trials, 6:262
Double-layer capacitance, 1:123
Drive mechanism, ventilator, 6:506
Dropfoot, correction of, 3:126127
Drug carriers
ethosomal, 2:477
liposomal, 2:466473
niosomal, 2:473477
particle, 2:480486
ultradeformable vesicular, 2:479480
vesicular, 2:466480
Drugcyclodextrins complex, preparation
of, 2:453454
Drug delivery
biomaterials in, 1:277278
controlled, 2:437440
intravenous, 2:448
oral, 2:446447
polymers for, 5:390391
smart polymers for, 1:340
stimuli-responsive hydrogels for, 5:391
supramolecular aggregates for,
2:460464
transdermal, 2:442446
use of nanoparticles in, 5:5
Drug delivery devices
colloidal, 2:464486
economics of, 2:440
implantable, 2:439440, 440442
nanoengineered, 2:504
Drug delivery microchip, 1:424, 425f
Drug delivery systems, 2:437495. See also
Drug delivery devices
biodegradable polymeric, 2:504
development of, 2:438
future prespectives on, 2:486
implantable microfabricated, 2:504
microelectro-mechanical, 2:440452
microemulsions as, 2:461462
microflow regulator for, 2:504
molecular, 2:452460
principles of controlled drug delivery,
2:437440
Drug discovery, optical biosensors in, 5:173
Drug effect control, 1:4849
Drug effectiveness, disease progression
and, 5:273
Drug infusion pump, disposable, 2:502
Drug infusion systems, 2:495508
advancements in controller des1gn for,
2:504507
common, 2:496502
new developments in, 2:502504
tiny, 2:502503
Drug/lead discovery, use of microarrays in,
4:370
Drug-resistant hypertension, 1:15
Drugs
exposure-effect link in, 5:272273
implant failure and, 1:112
monitoring in anesthesia, 1:44, 48
Drug screening, cell-based, 4:140142
Drug testing, microbioreactors for, 4:393
Drug toxicity, as a complication of
parenteral nutrition, 5:128
Dry electrodes, 1:134
Dry heat sterilization, 6:275
Drying, of foam scaffolds, 1:293
DTA profile, 1:359
d-T (deuteron-tritium) reaction, in neutron
production, 5:6061
Dual-chamber arrhythmia detection, 1:7779
Dual-chamber pacemakers, 1:77
Dual-energy scanning, 2:244
Dual-energy X-ray absorptiometry,
1:552553
Dual-parameter histograms, 2:401
Dual-photon absorptiometry, 1:551552
Dual Purkinje image measurement,
3:277278
631
632
INDEX
INDEX
Electrocutaneous electrical stimulation,
6:296
Electrode arrays, high density, 2:138
Electrode assembly, in visual prostheses,
6:539
Electrodecell interface model, 4:138139
Electrode contact impedance standards,
1:162
Electrode-electrolyte impedance,
1:123124
Electrode-electrolyte interface, 1:122131;
3:106
simple equivalent circuit model of,
1:124125
Electrode-electrolyte potential,
1:122123
Electrode gels, 1:141
effects of, 1:134136
Electrode impedance, in
electroneurography, 3:117119
Electrode metals, 1:129131
Electrode placement, in transcutaneous
electrical nerve stimulation,
6:446448
Electrodermal activity (EDA), 1:173, 174
Electrodermal biofeedback amplifier, 1:173
Electrodermal biofeedback
instrumentation, 1:173174
Electrodermal electrodes, 1:173
Electrodes. See also CO2 electrodes;
Microelectrodes
basic types of, 6:446t
biomedical, 1:120166
bipolar and tetrapolar, 1:198199
blood gas, 1:465467
circumferential cuff, 3:123124
in conductance catheter systems,
1:206207
conductive, 1:145146, 146148
current density distribution under,
1:144146, 148
designing biomedical, 1:120121,
137158
dry, 1:134
EEG, 1:171172
EGG, 3:88
in electrical anesthesia, 3:29
for electrical stimulation, 3:351352,
354t
electrodermal, 1:173
EMG, 1:169; 3:102105
external electrostimulation,
1:142146
extraneural, 3:123125
flat interface nerve, 3:124
flexible, 2:12
garment, 1:149
gel-less, 1:134
hook, 3:125
implanted, 1:120121, 149158;
3:353357
for intraspinal stimulation, 3:357
intraneural, 3:120121
longitudinal intrafascicular, 3:111,
121122
modern designs for, 1:146149, 152154
modern disposable, 1:139141
633
634
INDEX
INDEX
End-tidal CO2, 2:(ETCO2), 20, 21
Energetic electron beam, 6:3
Energy, Anger camera, 1:58. See also
Surface energy
Energy absorption coefficients, 6:598
Energy-dispersive spectrometer (EDS),
1:356
Energy-dispersive X-ray analysis (EDX),
4:435
Energy fluence, photon, 6:591
Energy parameters, X-ray beam, 6:599
Energy resolution, Anger camera, 1:60
Energy storage, in human body, 1:191
Energy Storage and Return (ESAR)
prosthetic feet, 4:553
Energy transfer coefficients, 6:598
ENG recording configurations, 3:112117.
See also Electroneurography (ENG)
Engine, microheat, 4:433
Engineered tissue, 3:189210
biocompatibility of, 3:201
bioreactor technology and, 3:200
cryopreservation of, 3:201202
examples of, 3:202205
future prospects for, 3:205206
growth of, 3:191
history of, 3:189190
immune concerns related to, 3:192
properties of, 3:200201
scaffolds in, 3:194200
signals in, 3:198200
spatial organization in, 3:199
theory behind, 3:190202
Engineering, biosurface, 1:409417
Engineering Accreditation Commission,
1:404
Engineering evaluation form, 3:219t
Engineering in Medicine and Biology
Society (EMBS), 4:316
Enhanced resolution techniques, in
electrophoresis, 3:134138
Enterococci, 1:114
Enterprise level PACS, 6:309
Entropy-based neurological monitor, 5:39
Environmental control, 3:210215
feature control in EADL systems,
3:212213
power switching and, 3:210212
subsumed devices in EADL systems,
3:213214
Environmental noise, reducing, 1:234235,
236f
Environmental pathogens, classification
of, 1:113114
Environmental probes, fluorescent,
4:468469
Environmental Protection Agency (EPA),
2:155
Environmental rounds, conducting, 3:228
Environmental temperature, for infant
incubators, 4:148
Environment-induced cracking (EIC),
1:311
Enzymatic conversion, 2:193194
Enzyme activity, in white blood cells, 2:411
Enzyme electrode glucose sensors
based on conductive polymers, 3:399400
635
636
INDEX
Excitation
in functional electrical stimulation,
3:348350
in linear variable differential
transformers, 4:253
Excitation frequency, in linear variable
differential transformers, 4:255
Excitation microscopy, multiphoton,
2:9394
Excitation wavelengths, 3:346
Executive Information System (EIS), 5:131
Exercise(s)
feedback control of, 1:398400
principles for, 1:391393
for rehabilitation, 1:398
for scoliosis, 6:130
thermoregulation and, 1:191
Exercise (stress) electrocardiography,
3:4748
Exercise equipment
feedback control of, 1:398400
hydraulic, 1:397398, 398399
weight-based, 1:397
Exercise fitness biomechanics, 1:384403
exercise and training principles,
1:391393
feedback control of exercise, 1:398400
future developments in, 1:400401
high technology tools and, 1:393398
quantifying motion, 1:384391
Exercise physiology, basic principles of,
3:251t
Exercise protocols, in exercise stress
testing, 3:251
Exercise stress testing, 3:246263
angiographic disease prediction and,
3:256257
biomarkers in, 3:255256
blood pressure measurement in,
3:247248
computerization in, 3:249
ECG recording in, 3:248, 249, 250
echocardiography in, 3:255
equipment for, 3:247256
evaluation in, 3:256262
lead systems in, 3:248249
modalities in, 3:250251
noise in, 3:249250
nuclear techniques in, 3:254255
postexercise period in, 3:252253
prediction of restenosis with, 3:258259
protocols in, 3:251252
Exercise test, ACC/AHA guidelines for
prognostic use of, 3:259262
Exercise test modalities, in exercise stress
testing, 3:250251
Exopolymer production, in biofilms, 1:115
Expected oxygen tension, 6:105
Experimental dosimetry, 1:614615
Experimental neural prosthetic systems,
3:128129
Expert systems, machine-based, 2:317
Expiration, forced, 5:432
Expiratory reserve volume (ERV), 6:100
Exposure limits, electrical and magnetic
field, 2:183t
External anal sphincter (EAS), 1:62, 65
INDEX
Fatigue, due to corrosion, 1:311
Fatigue issues, public awareness of, 3:543
Fatigue strength, of bone, 1:531
Fatigue wear, 1:315
Fauchard, Pierre, 1:326
FDA Modernization Act (FDAMA), 4:315.
See also Food and Drug
Administration (FDA)
FDA quality system regulations, 2:150152
FDA-regulated entities, 2:142
F (Fisher) distribution, 6:255t
Feature-based algorithms, in arrhythmia
analysis, 1:7677
Feature extraction
alternatives to, 2:296
in automated cytology, 2:403
in computer-assisted detection/
diagnosis, 2:295296
EEG, 3:7475
Feature extraction/classification, using IR
imaging, 6:352
Feature recognition systems, 3:269270
Fecal incontinence
biofeedback clinical outcome literature
related to, 1:180, 182
manometric features of, 1:65
Feedback control
of exercise, 1:398400
in incubators, 4:153
of movement, 1:385386
in thermoregulation, 1:191
Feedback controlled drug delivery, 2:439
Feedback operation, in the atomic force
microscope, 4:506508
Feet, prosthetic, 4:552553
Fegler, G., 2:25
Feldspar, in porcelain, 1:326
Feldspathic porcelain, 1:326
Female condoms, 2:339340
Female human sexual behavior
instruments and measurement of,
6:149150
treatment of, 6:153155
Female sexual behavior assessment,
6:150153
external measurement devices for, 6:153
internal devices for, 6:150152
Female sexual dysfunction, treatment
articles on, 6:154155
Fenn, Wallace O., 5:430
FES devices/systems, 3:350358. See also
Functional electrical stimulation
(FES)
Fetal activity monitoring, 3:299
Fetal blood gas monitoring, 3:298299
Fetal cardiotocography, 3:296298
clinical applications of, 3:297298
Fetal electrocardiogram (FECG), 3:288
Fetal electroencephalography, 3:299300
Fetal heart, acoustic pickup of, 3:291
Fetal heart monitoring, signal processing
in, 3:288290
Fetal heart rate (FHR), 1:475
direct determination of, 3:288
indirect sensors of, 3:290293
monitoring of, 3:287293
Fetal hemoglobin, 2:40
637
638
INDEX
INDEX
Frequency dependence, of impedance,
3:117119
Frequency domain analysis, 3:108
Fresh gas decoupling, in anesthesia
machines, 1:40
Fretting-corrosion, 1:311
Freund phalloplethysmograph, 6:154f
Fricke dosimeter, 5:473
Fricke gels, 5:484485
Friction, 1:314
Friction coefficients, of diamond-like
carbon coatings, 1:318
Friedman test, for matched samples, 6:259
Fringe effects, with metal electrodes,
1:146148
Frontal electrode placement, for
biofeedback, 1:177
Frontalis electromyogram (FEMG), in
anesthesia monitoring, 1:44
Frontal plane, scoliosis and, 6:122
Fuel cell, in solid electrolyte cell oxygen
analyzers, 5:204205
Full field digital mammography, 4:303304
Full field digital mammography (FFDM)
systems, 4:302, 304305
imaging characteristics of, 4:305t
Full-body CT screening, 2:264
Fuller, Buckminster, 1:298
Fullerenes, 1:297298, 305306
Fullerite, 1:298
Full-field optokinetic response, 5:140
Full film lubrication, 1:315
Full-thickness injuries, 2:72
Functional angiological thermatomes,
6:349
Functional ankylosis, 1:328
Functional deficit scale, injury-related,
6:179180
Functional electrical stimulation (FES),
3:347366. See also FES devices/
systems
controllers and control strategies in,
3:357358
electrode designs for, 3:351357
theory and application of, 3:348350
therapeutic effects of, 3:358359
Functional magnetic resonance imaging
(fMRI), 4:289290
Functional mapping, presurgical,
1:244245
Functional residual capacity (FRC), 5:437
by plethysmography, 5:438
Functional stereotaxis, 6:268
Fundus camera, 5:291
Fundus photos
clinical evaluation of age-related
macular degeneration in,
5:293294
stereo, 5:293
Fundus reflectometry, 5:135136
clinical applications of, 5:136
Fungi, electron microscopic diagnostic
criteria for, 4:485
Fusion bonding, 2:3, 4f
Fusion cage stabilization, interbody,
3:578579
Fuzzy logic systems, 2:317319
639
640
INDEX
ambulatory, 1:1617
home, 3:395396
Glucose-sensitive microtransponder,
1:424, 425f
Glucose sensors, 1:1617; 3:393406
blood glucose prediction and, 3:402
challenges for development of, 3:402
ideal, 3:395
new, 3:393395
noninvasive, 1:17
optical, 5:164165
sensing methodologies and, 3:395402
Glucose system, 5:126127
Glycosaminoglycan (GAG) side chains,
2:64
Gold, in dentistry, 1:322
Goldmann perimetry, 6:529
Gold thin-film electrodes, 1:156157
Goodness of fit test, 6:248249
Good Samaritan legislation, 2:49
Gorlin formula, 2:19
Gott, Vincent, 1:302
Government regulation. See Regulation
GPS navigational aids, for the visually
impaired, 1:451453
Gradient recalled echo (GRE) imaging,
4:288289
Gradient separation, of peripheral blood
mononuclear cells, 1:461464
Gradiometers, 1:233234, 235236
Graft dysfunction, after liver
transplantation, 4:271
Grafted polymer layers, 1:347
Grafts
hyperbaric medicine and, 4:25
vein, 6:494
Gram-negative bacteria, 1:319320, 371
Gram-positive bacteria, 1:320
Granuloma pouch, 1:111
Graphene structure, 1:297
Graphic audiograms, 1:9596
Graphic recorders, 6:4862
analogue, 6:5559
analogue and digital, 6:4951
chart abscissa generation in, 6:51
digital, 6:5960
evaluation of, 6:6062
galvanometric, 6:5558
graphic quality of, 6:5355
manufacturers of, 6:61t
recording accuracy in, 6:5153
translational servorecorders, 6:5859
Graphic recording, fundamental aspects of,
6:4955
Graphics display, in neurolog1cal
monitors, 5:34
Graphite(s), 1:296, 297
synthetic, 1:299
Graphite-loaded polyesters, in electrodes,
1:131
Gravity drip drug infusion systems,
2:497498
Green Cross Corporation, 1:514
Green strain tensor, 1:88
Grid computing, 6:309
Gross tumor volume (GTV), 5:545, 546;
6:32
Grounding, in electroneurography,
3:116117
Ground substance, in skin, 6:204
Group change, versus individual change,
5:451
Groupware systems, in office automation
systems, 5:156158
Growth factors
for modulating cell behavior, 2:74
in tissue engineering, 1:366
Guardian real time system
(Guardian1 RT), 1:16
Guidances, Nuclear Regulatory
Commission, 2:171
Guidant Galileo delivery device, 1:607608
Guidant Galileo IVB system, 1:605609
Guidant ICD algorithm, 1:75
Guidant Ventak AV III DR algorithm, 1:78
GuideCane, 1:450451
Guidewire diagnostics
in coronary angioplasty, 2:349360
issues in, 2:353354
Guide wire perturbation, 1:609610
Guidewires
in coronary angioplasty, 2:349350
increased pressure drop and reduced
hyperemic flow due to, 2:355357
in microsurgery, 4:532
nickeltitanium shape memory alloy, 1:8
Guiding catheter, in coronary angioplasty,
2:349
Guluronate junction zone, 1:370f
Guyton model, 5:302303
Gynecological diseases, cryosurgical
treatment of, 2:374
Gynecologic electrosurgery, 3:160161
Gynecology, high intensity focus
ultrasound for, 4:78
Haar (square) wavelet, 1:75
Hagen, Gotthilf Heinrich Ludwig, 1:504
Hagen-Poiseuille law, 1:504
Hair follicles, 1:133
Haldane effect, 1:469
Half-cell potential, 1:122123
Half-value layer (HVL), 6:592, 599
determination in X-ray equipment, 6:566
Hamilton, W. F., 2:25
Hand-cycling, 4:549
Hand grasp, restoration of, 3:127
Handheld electrodes, 1:143
Hand surface temperature biofeedback,
with tension and headache, 1:176
HAPEX composite, 1:289
Haptic feedback, in microsurgery,
4:528529
Haptic icons, 6:299
Hard copy output device, in neurological
monitors, 5:34
Hard wall contact, 1:351
Hardware
computer networking, 5:350351
medical image display, 5:353355
phonocardiography, 5:289
visual prosthesis, 6:536539
Harmonic excitation, coded, 6:469471
Harmonic imaging, 3:45; 6:468469
INDEX
Haversian bone, 1:528
remodeling of, 1:534535
Haversian canals, 1:524
Hazard assessment, ultraviolet radiation,
6:487488
HBOC-201 (Hemopure), clinical trial of,
1:518519
Headache. See also Migraine headache
biofeedback clinical outcome literature
related to, 1:178179
biofeedback training and, 1:167168
Head and neck cancer, treatment planning
for, 5:538
Headgear, in continuous positive airway
pressure, 2:335
Head holder, 5:588589
Head Injury Management Guidelines,
4:578
Head motion, measuring point-of-gaze in
the presence of, 3:273275
Head-mounted video-based eye tracking
systems, 3:279280
Head stereotactic localizer, 5:594
Healing
regeneration versus repair in, 6:180
response to biomaterials, 1:108109
Health, in older people, 1:390
Healthcare, problems with, 6:109114
Healthcare information systems, 4:310
Healthcare process, increased patient
participation in, 3:542543
Health Insurance Portability and
Accountability Act (HIPAA), 1:456
Health issues, nanoparticle-related,
5:710
Health On the Net Code of Conduct
(HONcode), 4:309
Health Physics Society, 4:320
Health status measures, clinical
significance of, 5:444445
Healthy organs
composed of separately critical voxels,
6:46
integral response for, 6:4546
Healthy subjects, EGG in, 3:9192
Healthy tissue integral dose, 6:43
Hearing. See also Audiometry; Ear entries
assessment of, 2:215
assistive devices related to, 2:222
Hearing aids, 2:224
Hearing analysis software, 2:214
Hearing disorders, new directions in, 2:224
Hearing impairment, categories of, 2:211
Hearing intervention, 2:218219
Heart. See also Artificial heart; Cardiac
entries; Cardio- entries; Myocardial
entries; Pacemaker entries
anatomy and function of, 3:450
conducting system of, 2:43
electropuncture of, 1:150
hemodynamic monitoring of, 4:566567
pressures and flows in, 3:450t
as a pump, 3:477483
sounds and murmurs from, 5:279282
Heart-arterial coupling, 3:492494
Heart beat detection, computer-based,
3:5051
641
Heat loss
by human body, 1:191
predictable, 2:28
Heat-related hyperemic response, 2:379
Heat sterilization, 6:275276
dry, 6:275
moist, 6:275276
Heat transfer
effects of blood perfusion on, 1:189190
in human body, 1:191
Heat transfer components, in
microbioreactors, 4:389
Heavy ion radiotherapy, 6:113
in cancer therapy, 6:1011
electron-beam, 6:46
fast and slow neutron radiotherapy,
6:68
future developments in, 6:1113
Heimlich maneuver, 2:5556
Helical computed tomography, 2:233
Helical CT scan, 2:238
Helical tomotherapy, 6:398399
Helicobacter pylori urease analyzer
(HPUA), 4:105
Helium dilution, 5:438
Hematocrit (HCT), 2:87
effect on blood viscosity, 1:501f
impedance plethysmography and, 4:130
Hematocrit measurement, 1:208
optical sensors in, 5:170171
Hematogenous infection, 1:117118
Hematological malignancies, treatment of,
4:606
Hematology, automated cytology in, 2:404
Hematology analyzers, 2:89t
automated, 2:410
Hematology systems, WBC differential
analysis on, 2:414419
Hematopoietic stem cells (HSCs), 6:382
Hemiarthroplasty, 3:514
Hemiarthroplasty hip replacements, 3:522
Hemisurface hip replacements, 3:522
Hemobilia, 3:391
Hemocytometer, 2:8283
Hemodynamic evaluation, of prosthetic
heart valves, 3:439441
Hemodynamic monitoring, 4:565576. See
also Blood pressure monitoring
bedside, 4:567568
cardiac output determination in,
4:573574
checking dynamic response in, 4:570572
computerized decision support in, 4:575
heart, 4:566567
measurements in, 4:568569
neonatal, 4:593594
signal amplification, processing, and
display in, 4:572573
theory behind, 4:566
Hemodynamic monitoring system,
technical management of, 4:593594
Hemodynamic parameters, alarming based
on, 4:574
Hemodynamics, 3:477497. See also Blood
entries; Heart
arterial system and, 3:483492
heartarterial coupling and, 3:492494
642
INDEX
Hemodynamics (Continued)
heart valve, 3:427428
peripheral, 4:127128
Hemoglobin (Hb), 1:500; 2:14
in blood oximetry, 1:470471
in blood oxygen transport, 1:467468,
469
cardiopulmonary resuscitation and,
2:4041
encapsulated, 1:520
oxygen saturation of, 6:523
PFCs and, 1:514
Hemoglobin concentration (HGB), 2:87
Hemoglobin solutions, 1:516520
in clinical trials, 1:517t, 518520
duration of action of, 1:518
formulation of, 1:516517
hematopoietic effect of, 1:518
hemodynamic effects of, 1:517518
Hemolink, clinical trial of, 1:519520
Hemolysis, 1:461
Hemopure, clinical trial of, 1:518519
Hemorrhage, gastrointestinal, 3:384393
Hemostasis, biomaterial failure and, 1:280
HendersonHasselbalch method, 2:110
Henrys law, 1:465; 4:19
Hepatic artery thrombosis, 4:271. See also
Liver entries
Hepatic failure, diseases associated with,
4:268t
Hepatic vein thrombosis, after liver
transplantation, 4:271272
Hepatitis, from banked blood, 1:512513
Heterografts, 1:283
Heuristic sequence alignment methods,
1:219
Hewlett-Packard ear oximeter, 1:471
Hi-ART II CT imaging system,
6:399401
Hi-ART II tomotherapy unit, 6:398399
Hidden Markov Model (HMM), 1:222
Hierarchical storage management/
compression, 5:349
HIFU apparatus, 4:80f. See also High
intensity focus ultrasound (HIFU)
HIFU devices, 4:7576
High angle annular dark field (HAADF)
mode, 4:478
High blood pressure. See Hypertension
entries
High contrast spatial resolution, in CT
scanners, 6:576577
High Density Avalanche Chamber
(HIDAC) PET system, 5:411
High density electrode arrays, 2:138
High density polyethylene (HDPE), 1:333
High dose rate (HDR) brachytherapy,
1:590601; 6:2627. See also Highdose-rate remote afterloaders
advantages and disadvantages of, 1:600
costs associated with, 1:599600
quality assurance in, 1:599
shielding in, 1:598599
treatment planning system for,
1:597598
High-dose-rate remote afterloaders
components of, 1:590594
INDEX
Hospital information system (HIS),
interfacing with radiology information
system, 5:335
Hospital safety program, 6:109122. See
also Total hospital safety program
medical devices and instrumentation
related to, 6:117119
patient safety in, 6:119120
tools for, 6:119
Host-related risk factors, for implantrelated infections, 1:114115
Hot packs, 1:190
Hotspots, current density, 1:121
Human allograft (cadaver skin), as a skin
substitute, 6:173174
Human amnion, as a skin substitute, 6:174
Human anatomy, 1:384f
Human body, oxygen transport in,
5:209210
Human body temperature profile,
simulated, 6:348f
Human clinical models, of spine
stabilization procedures, 3:582585
Human factors
alarms and, 3:540541
automation and, 3:541
case studies of, 3:538539
cognitive task analysis and, 3:540
labeling and, 3:541
legal influences that affect, 3:539
in medical devices, 3:536547
methods to improve design of, 3:539540
new issues involving, 3:542544
reporting and, 3:541542
user testing and, 3:540
work domain analysis and, 3:540
Human Factors and Ergonomics Society,
4:320
Human factors engineering perspective,
3:537538
Human immunodeficiency virus (HIV)
patients, medical procedures for,
3:543544. See also HIV entries
Humanitarian use devices, 2:146
Human joints. See also Joints
characteristics of, 4:206t
finite element analysis of,
4:218219
Humanoid phantom, 5:265266
Human organ weights, 5:572t
Human patient simulators (HPS), 1:4546
Human performance, analyzing, 1:394
Human spine, 6:230
Human spine biomechanics. See Spine
biomechanics
Human thermal models, 6:347348
Humidity, in continuous positive airway
pressure, 2:335336
Humoral immune response, 1:113
HunterRoth intramyocardial electrode,
1:151
Hurter and Driffield curve (H&D curve),
6:142143
Hutchinson, 5:John, 430
Hyaff, 1:340
Hyaline cartilage, composition and
structure of, 2:6365, 66
643
Hylan, 1:340
Hyperalgesia, 6:439440
Hyperbaric chamber, 4:21
Hyperbaric chamber facility design, 4:27
Hyperbaric medicine, 4:1829
acute exceptional blood loss anemia and,
4:26
acute thermal burns and, 4:26
acute traumatic ischemias and, 4:2326
air embolism in, 4:22
approved indications for, 4:2021
carbon monoxide poisoning and, 4:26
contraindications for, 4:2122
cyanide poisoning and, 4:27
decompression illness and, 4:23
flaps and, 4:2425
frontiers and investigational uses of,
4:2728
historical background of, 4:18
physics of, 4:1819
physiology of, 4:1920
radiation tissue damage and
osteoradionecrosis in, 4:26
refractory osteomyelitis and, 4:26
skin grafts and, 4:25
wounds and, 4:2324
Hyperbaric oxygenation (HBO), 4:2933
Hyperbaric oxygen therapy, approved uses
for, 4:18t
Hyperemic flow, during guidewire
diagnostics, 2:355357
Hyperemic response
heat-related, 2:379
nerve-axon-related, 2:379380
Hyperglycemia, 1:17
Hyperlipidemia, parenteral nutrition and,
5:132133
Hyperpolarized contrast agents, in
magnetic resonance imaging, 4:294
Hypertension. See also Ambulatory blood
pressure monitoring
arterial mechanics in, 1:8990
biofeedback clinical outcome literature
related to, 1:180
borderline, 1:15
defined, 1:491
drug-resistant, 1:15
with end-organ damage, 1:15
episodic, 1:15
labile, 1:15
in pregnancy, 1:16
white-coat, 1:15
Hypertension monitoring, transthoracic
bioimpedance and, 1:202
Hyperthermia, 1:188189. See also
Systemic hyperthermia; Ultrasonic
hyperthermia
application modes for, 4:6875
chemotherapy in conjunction with,
4:68
devices, 4:7576
effect on tumors, 4:49
endocrine function and, 4:48
externally applied, 4:6873
future perspectives in use of, 4:8183
immune system and, 4:5051
interstitial, 4:3442
644
INDEX
Hyperthermia (Continued)
medical applications of, 4:67
nanoparticle therapy and, 4:49t
radiation coupled with, 4:6768
step-down sensitization in, 4:49
Hyperthermia and chemotherapy clinical
trials, 4:70t
Hyperthermia and radiation clinical trials,
4:69t
Hyperthermia devices, commercially
available, 4:47t
Hyperthermia systems, commercially
available, 4:4546
Hypertrophy, developing, 1:391
Hypoglycemia, 1:17
Hypoperfusion, 6:164
Hypopnea, 6:220. See also Obstructive
sleep apnea/hypopnea syndrome
(OSAHS)
Hypotension, orthostatic, 1:16
Hypothalamus, thermoregulation and,
1:190, 191
Hypothermia, 1:188189, 191
Hypothesis testing, parametrical, 6:251
Hypothetical distribution
comparing sample distribution to,
6:257258
one-sample t-test to compare one data
sample to, 6:251253
Hypovolemia, 2:48
Hypovolemic shock, 6:164
management of, 6:168
Hysteresis, in surface analysis, 1:348349
125
ultrasonic, 6:453473
vascular, 2:426; 4:291292
Imaging artifacts, 5:494
Imaging atomic force microscope (AFM),
4:504505, 506510
Imaging atomic force microscopy,
evaluation of, 4:513514
Imaging books/reports, 4:343344
Imaging devices/equipment/instruments,
4:8997
animal, 5:104106
electronic portal imaging detectors,
4:8990; 5:484
hybrid, 5:103104
liquid ionization chambers, 4:9092
near-field, 4:436439
physical aspects of, 4:90
Imaging fiber bundles
flexible, 3:307308
rigid, 3:308309
Imaging modalities, based on fluorescent
microscopy, 4:498502
Imaging modes, 6:468471
Imaging sequences, in magnetic resonance
imaging, 4:288
Imaging system, in the transmission
electron microscope, 4:481
Imaging techniques, for exercise stress
testing, 3:253
Imaging units, regulations related to, 2:174
131
I-MIBG therapy, dosimetry of,
5:569570. See also 125I (iodine-125)
Immature cells, in tissue engineering,
6:382
Immitance measurement, acoustic,
1:99101
Immune adjuvant, use with T cell
administration, 4:113
Immune reactions. See also Immune
response
from banked blood, 1:513
to implants, 1:112
Immune response, 1:113. See also Immune
reactions
biomaterial failure related to, 1:280281
cells participating in, 4:597
Immune system
antibodies and, 4:597599
effect of UV exposure on, 6:476
whole-body hyperthermia and, 4:5051
Immunization, 4:597
Immunoassay analyzers, 1:21, 22t
Immunoassays
development of, 4:375
in microbial detection, 4:376
Immunoblotting, 4:603
Immunocytochemistry, 2:411
Immunoelectron microscopy, 4:602
Immunoelectrophoresis, 4:603
Immunofluorescence, 3:345346;
4:601602
Immunohistochemistry, 4:602
Immunologically sensitive field-effect
transistors (IMFETs), 4:98110
direct-acting (label-free), 4:100102,
103104
future directions for, 4:108109
INDEX
indirect-sensing, 4:102103, 104107
practical limitations of, 4:107108
theory behind, 4:99103
Immunology, automated cytology in, 2:405
Immunomodulation, transfusion-related,
1:513
Immunosensors, 5:172173
piezoelectric sensors as, 5:363365
Immunosuppressive agents, 4:274t
alternative, 4:275
Immunosuppressive medications, 4:273
Immunotherapy, 4:111120
activation and polarization of effector T
cells, 4:112113
adoptive T cell immunotherapy of cancer
in lymphopenic host, 4:115116
antitumor reactivity of T cell subsets,
4:114115
cancer, 4:605
combined, 4:117118
effector T cell trafficking and
proliferation, 4:113114
induction of tumor-reactive pre-effector
T cells, 4:111112
redirecting effector T cells to tumor,
4:116117
use of immune adjuvant with T cell
administration, 4:113
Impedance, 1:99. See also Tissue
impedance
acoustic, 4:66t; 6:454455
electrode-electrolyte, 1:123124
at electrode-skin interface, 1:121
frequency dependence of, 3:117119
interface, 1:124
limit current of linearity and, 1:128129
skin, 1:131137
Impedance analysis, 3:483485
of tissue and suspended cells, 4:135137
Impedance cardiography waveforms,
1:201f
Impedance mapping, 6:372
Impedance plethysmography, 4:120132;
5:238239
bioimpedance measurement
fundamentals, 4:122124
characteristics of bioimpedance,
4:124126
instrumentation and applications for,
4:127131
laboratory applications of, 4:130
methodology of, 4:120122
model-based relations for volume
determination, 4:126127
Impedance plot, complex, 1:124
Impedanceresistance measurements, in
cryosurgery, 2:370372
Impedance spectroscopy, 4:132144
in adherent cell monitoring, 4:137138
data presentation and analysis related
to, 4:134135
electrodecell interface model and,
4:138139
instrumentation for, 4:133134, 138
for monitoring cell attachment/
spreading, 4:139140
theory behind, 4:133
645
preventing, 1:117118
risk factors for, 1:114115
treating, 1:116117
Implants. See also Cochlear prostheses
bioactive glasses in, 1:286
biocompatibility of, 1:256
bone cement, 1:540
carcinogenicity and, 1:112113
ceramic, 1:260262
cochlear, 2:133, 139
composite, 1:262264
contraceptive, 2:344345
dental, 1:327329; 6:426427
for degenerative bone disease, 6:234
for degenerative disk disease,
6:234237
for developmental spine deformities,
6:234
epiretinal, 6:534535
history of, 1:255
immune reactions to, 1:112
interfacial stability of, 1:284
long-term problems with, 1:255
materials for, 1:255
prostate seed, 5:418429
resorbable, 1:255256
spinal, 6:229240
subretinal, 6:534
tissue response to, 1:109110
transplants versus, 1:283284
Implant sites, characteristics of, 1:108
Implant surfaces, 1:130
Impressed currents, 1:238
Impulse response, in compartment
modeling, 6:433
Incandescent ultraviolet radiation, 6:476
Incidentaccident investigation/reporting,
6:118119
methodology for, 6:119
Inclusion complexes, formation of, 2:453
Inconsistent data, in computed
tomography, 2:255
Incontinence, biofeedback clinical outcome
literature related to, 1:182
Incubator dynamics, 4:153155. See also
Infant incubators
Incubator studies, 4:150152
Independent Component Analysis (ICA),
1:241242
Independent living aids, for the sight
impaired, 1:447448
Indexers, in remote afterloaders,
1:591592
Indication for use statement, 2:146
Indicator dilution, principle of, 2:26
Indicator dilution approach, in peripheral
vascular noninvasive measurements,
5:246
Indicator dilution cardiac output
measurement, fundamental equations
for, 2:22
Indicator dilution curve, fundamental
equations for, 2:2223
Indicator dilution equations, application of,
2:23
Indicator-mediated transducers, in optical
sensors, 5:163
646
INDEX
INDEX
Integrated circuits, in temperature
measurement electronics, 6:331332
Integrated-circuit temperature sensor,
4:157162
applications for, 4:160161
circuits and devices in, 4:159160
future of, 4:161162
theory behind, 4:158159
Integrated gas analyzers, anesthesia
machine, 1:40
Integrated humanmachineenvironment
systems, in anesthesia monitoring,
1:44
Integrated monitors, anesthesia machine,
1:3940
Integrated optic oxygen sensor chip, 5:206
Integrating the Healthcare Enterprise
(IHE), 5:334
Integration
in electromyography, 3:107
in microbioreactors, 4:392
Integratorinverter circuit, 1:194
Integrity, in teleradiology, 6:307308
Intelligent electronic travel aids, 1:450
451
Intelligent humanmachine interface, in
anesthesia monitoring, 1:44
Intelligent navigational aids, for the
visually impaired, 1:453
Intensifying screen
absorption efficiency and conversion
efficiency of, 6:139140
physical properties of, 6:139
in screen-film systems, 6:138140
Intensity-modulated arc therapy (IMAT),
5:492, 523
Intensity-modulated radiation therapy
(IMRT), 5:520525, 460461
computed tomography simulation for,
2:273274
gel dosimeters in, 5:491492
Interaction coefficients, in radiation
measurement, 5:465466
Interaction types, in radiation therapy
dose calculation, 5:535
Interactive localization device (ILD), 6:270
Interbody cages, 6:235
lumbar, 3:580581
Interbody fusion cage stabilization,
3:578579
Intercalated disks, 2:43
Intercapillary space, 2:199200
Intercompartmental fluid shifts,
impedance plethysmography and,
4:129
Intercostal EMG measurements, 6:521
Interface electronics, in biotelemetry
systems, 1:418
Interface impedance, 1:124
Interfaces, in continuous positive airway
pressure, 2:335
Interfacial bonding, of bioactive glasses,
1:286
Interference, in biomedical electrodes,
1:121
Intergranular corrosion, 1:311
Interictal spikes, 1:245
647
648
INDEX
INDEX
IORT units
conventional versus mobile, 6:21
dedicated, 6:1718
mobile, 6:1820
IP telephony, in office automation systems,
5:159
IR absorption technique, 6:526. See also
Infrared entries
IR-based breast screening, concept
validation in, 6:352353
IR cameras, 6:361
IR fibers, 3:304
IR image processing, smart, 6:351
IR imaging
in early breast cancer detection,
6:349
for feature extraction/classification,
6:352
IR imaging activities, international,
6:353354
Irradiance, weighted, 6:478479
Irradiation
e-beam, 6:278
in neutron activation analysis, 5:44
Irritable bowel syndrome, biofeedback
clinical outcome literature related to,
1:180
Irritative zone, 1:245
Isaacs, James, 2:37
Ischemia detection, 1:210211
Ischemias, hyperbaric medicine and,
4:2526
Ischemic atherosclerotic disease, 2:5051
Ischemic colitis, 3:392
Ischemic injury, after liver
transplantation, 4:272
Ischemic stroke, 2:5253
ISFET circuits, 4:191193. See also Ionsensitive field-effect transistors
(ISFETs)
ISFET field-effect transistor-based
chemical sensor, 6:527
Isocyanates, for polyurethanes, 1:337
Isodose charts, 2:131132
Isodose curves, 6:589
Isoelectric focusing (IEF), 2:106
Isokinetic training, 1:392, 393
Isometric exercises, 1:391392
Isometric muscle tests, 6:63
Isosbestic point, 1:470
Isotactic polypropylene, 1:335
Isotonic resistive training, 1:392, 393
Isotope selection, for prostate seed
implants, 5:419
Isotropic fluidized-bed pyrolytic carbons,
1:300, 302303
Italy, infrared imaging in, 6:354
Iterative reconstruction techniques,
2:246247
Itrel I neurostimulator, 1:432
IUD, with danazol, 6:154. See also
Intrauterine devices
Japan, infrared imaging in,
6:353
Japanese clinical trials, of BNCT for brain
tumors, 1:579
649
650
INDEX
INDEX
Liquid-solid chromatography, 2:104
Liquid ventilation, with
perfluorochemicals, 1:516
Lister, Joseph, 1:267
Literature, intracranial pressure
monitoring, 4:580582
Lithographie, Galvanik, Abformung
(LIGA), 4:527
Lithotripsy, 4:258266. See also
Lithotripters
acute and chronic injury with, 4:263t
advances in, 4:263264
clinical results of, 4:261
history and evolution of, 4:258
principles of, 4:258260
safety and efficacy advances in, 4:264
stone fragmentation in, 4:260261
tissue injury with, 4:261263
treatment strategy modifications in,
4:263264
Lithotripters
advances in, 4:263
literature comparison of, 4:262t
Liver(s). See also Hepat- entries
bioartificial, 4:393
effects of parenteral nutrition on, 5:131
Liver cancer, high intensity focus
ultrasound for, 4:7677
Liver susceptometer, 1:238f
Liver tissue, engineered, 3:202203
Liver transplantation, 4:266277
acute cellular rejection after, 4:272
alternative immunosuppressive agents
and, 4:275
antiproliferative agents and, 4:275
biliary compl1cations following, 4:272
calcineurin inhibitors and, 4:275
chronic rejection following, 4:272275
contraindications to, 4:269
corticosteroids and, 4:273274
early complications of, 4:271
etiology of diseases requiring, 4:268269
history of, 4:266267
IL-2 receptor blockers and, 4:274275
immunosuppressive medications and,
4:273
indications for, 4:267268
initial results of, 4:267
ischemic and preservation injury
following, 4:272
portal and hepatic vein thrombosis after,
4:271272
posttransplantation management
associated with, 4:271
recipient characteristics and
prioritization for, 4:269270
recurrence of primary disease following,
4:273
source of organs for, 4:270271
T-cell depleting agents and, 4:274
Living dermal replacement (LDR),
6:191
Living skin equivalent (LSE), 6:191192,
381
Loading, effect on joints, 4:204
Local heating, of organs, 1:190
Localized drug delivery, 2:438
651
652
INDEX
INDEX
Materials technology, for prosthetic heart
valves, 3:441442
Mathematical cardiac torso (MCAT), 5:121
Mathematical models
of cardiac cells, 3:144145
of joints, 4:212220
Mathematics books/reports, 4:349
MATLAB, 6:263
Matrix-assisted laser desorption/ionization
(MALDI), 2:106107
Matrix phase, of resin-based composites,
6:9495
Matter, X-ray interaction with, 6:590599
Matthes, Karl, 1:469, 471
Mature cells, in tissue engineering, 6:382
Maxillofacial resin materials, 1:327
Maximal Expiratory FlowVolume
(MEFV), 6:102
Maximal heart rate studies, 3:257t
Maximal voluntary ventilation, 5:439
Maximizing performance, 1:387
Maximum dose to peripheral dose ratio
(MDPD), 5:583
Maximum intensity projection, in
computed tomography, 2:239
Maximum safe temperature rise
standards, for electrodes, 1:161162
Maxwell, James C., 1:197
Mean arterial pressure (MAP), 1:486, 487,
491499
Mean corpuscular hemoglobin (MCH), 2:87
Mean corpuscular hemoglobin
concentration (MCHC), 2:87
Mean free path (MFP), 6:593
Mean platelet volume (MPV), 2:87
Measurements, in electrophoresis,
3:138139
Mechanical environment, implant-induced
alterations of, 1:110
Mechanical events, in the cardiac cycle,
4:163
Mechanical heart valves, 3:411413,
445446
flow dynamics past, 3:417421
versus bioprosthetic heart valves,
3:446447
Mechanical models, of joints, 4:212220
Mechanical modulation, in engineered
tissue, 3:199
Mechanical properties
of acrylic bone cement, 1:546547
of surfaces, 1:343344
Mechanical signaling, in tissue
engineering, 6:388
Mechanical stimulation components, in
microbioreactors, 4:390
Mechanical strain gages, 6:283
Mechanical tactile stimulators, 6:293295
Mechanical vaporizers, in anesthesia
machines, 1:41
Mechanical ventilation, 6:107
Mechanical ventilatory support
adverse reactions to, 6:512513
goals of, 6:509510
indications for, 6:509
Mechanical work, thermoregulation and,
1:191
653
654
INDEX
electrode, 1:129131
as prosthetic restorative materials,
1:325326
Methyl methacrylate (MMA), 1:541542
Michigan Probe, 1:155, 156
Microarray analysis, 1:223224, 225f
fluorophores used for, 4:369t
Microarray experiment, washing step of,
4:364
Microarray images, quantification of, 4:365
Microarrays, 4:361371
basic principles of, 4:361366
data analysis for, 4:366
DNA, 2:433
equipment related to, 4:367370
fabrication of, 4:366367
as medical devices 370, 4:371
scanning, 4:365
Microarray scanners, 4:369370
Microbatteries, 4:429430
Microbial detection, piezoelectric sensors
for, 5:364
Microbial detection systems, 4:372383
development of, 4:375376
electronic nose, 4:381
fiber-optic fluoroimmunoassay systems,
4:378
future trends in, 4:381382
microchip technology, 4:380381
nanoparticle-based bio-barcode
technology, 4:379380
nucleic acid-based optical technologies,
4:376378
Microbioreactors, 4:383400
components of, 4:389392
design principles of, 4:385389
examples of, 4:393395
mechanical and material considerations
for, 4:387388
operation principles of, 4:386389
for optimizing production conditions,
4:393
for therapeutical applications, 4:394
for toxicological and drug testing, 4:393
for understanding biological responses,
4:394395
Microbolometer technology, 6:350
Micro capillary systems, 2:434
Microcapsules, implantable, 4:394
Microcard project, 1:156
Micro Cell Culture Analogs (CCAs), 4:393
MicroCHIP drug delivery chip, 1:425f
Microchips, drug delivery, 1:424, 425f
Microchip technology, 4:380381
Microcirculation, 1:515516
Microcirculation systems modeling,
5:313
Microcolony formation, in biofilms, 1:115
Microcomputer, in neurological monitors,
5:34
Microcontact printing (stamping), 1:409,
411, 412f
Microcontrollers, in temperature
measurement electronics, 6:330331
Microdialysis, 3:397
Microdialysis membrane dimensions,
4:403t
INDEX
Microdialysis probes, sensor attachment
to, 4:411
Microdialysis sample quantitation,
separations- based methods for,
4:409410
Microdialysis samples
analysis of, 4:409412
peptide and protein analysis of,
4:411412
Microdialysis sampling, 4:400420. See
also Microdialysis samples
applications of, 4:412413
clinical applications of, 4:413
detection types related to, 4:410411
device calibration in, 4:405409
evaluation and future use of, 4:413414
instrumentation components in, 4:402
principles of operation in, 4:402405
probe insertion trauma in, 4:408409
recovery, delivery, and localized infusion
in, 4:404405
sample volume limitations in, 4:409
simplified view of, 4:400401
uses for, 4:401t
Microdosimetric measurements, in
neutron beam therapy, 5:55
Microdosimetry, in the MIRD schema,
5:567
Microdrug delivery system, waterpowered, 2:504
Microelectrode arrays, 1:156
Microelectrodes, 1:154158
Microelectro discharge machining (microEDM), 4:527528
Microelectromechanical (MEMS) based
technology, 1:417418, 422, 423, 424,
427
Microelectro-mechanical drug delivery
systems, 2:440452
Microelectromechanical systems (MEMS),
1:509510; 2:1; 4:333, 527. See also
MEMS sensors
fabrication of, 4:527528
Microemulsions, 2:460461
as drug delivery systems, 2:461462
ophthalmic application of, 2:463
transdermal application of, 2:462463
Microfabricated drug delivery system,
implantable, 2:504
Microfabrication, 4:392
of electrodes, 1:155, 157
photolithography in, 4:425
Microflow regulator, for drug delivery
systems, 2:504
Microfluidic channels
fabricating, 4:425
studies of vascular diseases in, 4:395
Microfluidic modeling, 4:422423
Microfluidic networks (mFNs), patterning
via, 1:412413
Microfluidics, 4:333, 420427
biomedical applications of, 4:426427
fabrication in, 4:425426
pumping fluids, 4:423425
theory of, 4:420423
Microfluidic systems, as assisted
reproductive technologies, 4:394
655
656
INDEX
INDEX
Multiple EM for Motif Elicitation (MEME),
1:222
Multiple-head gamma cameras,
5:99100
Multiple laminar streams
in microbioreactors, 4:390
to study subcellular biology and
chemotaxis, 4:394395
Multiple medical devices, potential
interaction of, 3:543
Multiple model adaptive control (MMAC),
1:495496
Multiple row and area detectors, 2:236237
Multiple sequence alignments, 1:219220
MUltiple SIgnal Classification (MUSIC),
1:241
Multiplexing, in biotelemetry systems,
1:420
Multiplier transformation, 1:395
Multipoint stainless-plate electrode, 1:138
Multipoint video conferencing, 5:159
Multipotent adult progenitor cells
(MAPCs), 6:382383
Multiscale image contrast amplification
(MUSICA), 5:342
Multislice CT, 5:529
Multivariate methods, 6:261262
Multiview radiography, for scoliosis,
6:126127
Multi voxel MRS, 5:79
Multiwindow spatial registration, Anger
camera, 1:60
Mu rhythm, 1:243
Murine cardiac ventricular cells, research
in, 3:145146
Murine ventricular action potentials,
computational modeling of, 3:146147
Muscle(s). See also Myo- entries
cardiac, 2:43
contraction of, 1:385, 391392
electrodes in or on, 3:353355
Muscle assessment methods, advanced,
6:6566
Muscle cells, in arterial walls, 1:85
Muscle dynamics, measuring, 6:6566
Muscle force assessment, stimulated,
6:6670
Muscle force assessment system, 6:68f
Muscle overload, 1:392, 393
Muscle performance, components of, 6:63
Muscle tension, biofeedback training and,
1:167168
Muscle testing, 6:6270
isometric, 6:63
manual, 6:6465
Muscle tissue, aging and, 1:389
Muscle tone
cooling and, 3:466
therapeutic heat and, 3:465
Muscular electrodes, 1:149
Muscular endurance, 1:391
Muscular strength, 1:391
Muscular system, integration of, 1:391
Musculoskeletal disease, magnetic
resonance imaging of, 4:296297
Musculoskeletal function, evaluation of,
6:8592
657
658
INDEX
Neoplasms
electron microscopic diagnosis of, 4:484
esophageal, 3:390
lower GI, 3:392
Nernst equation, 1:122123
Nerve-axon-related hyperemic response,
2:379380
Nerve electrodes, implanted, 3:355357.
See also Neural electrodes
Nerve growth factor (NGF), 1:375377
Nerve recordings, 3:110111
Nerve tissue, engineered, 3:205
Nervous system, 1:385386. See also
Neural entries; Neuro- entries
Net magnetization, creating, 4:283
Net Present Value (NPV) calculations, for
Mount Sinai total laboratory
automation, 1:2426
Net Present Value profile, for Mount Sinai
total laboratory automation, 1:27
Networked-Attached Storage (NAS),
5:530
Networking hardware, 5:350351
Networking software, 5:352353
Network security, 5:353
Neural electrodes, 1:149. See also Nerve
electrodes
encircling, 1:157
Neural net (NN) systems, 2:319320
Neural network approaches, to arrhythmia
analysis, 1:7677
Neural-network based blood pressure
controller, 1:497
Neural prosthetic systems, experimental,
3:128129
Neural signals, 3:111112
Neurodermatomal thermatomes, 6:349
Neuro-electronic interface, 3:110119
Neuroendoscopy, 3:185
Neurofeedback, biofeedback clinical outcome
literature related to, 1:181182
Neurological effects
of cooling, 3:466
of therapeutic heat, 3:465
Neurological monitors, 5:3241
classification of, 5:3233
common specifications of, 5:39
electrodes in, 5:3334
main components of, 5:3334
types of, 5:3539
Neurologic procedures, electrosurgery in,
3:159160
Neurology, high intensity focus ultrasound
in, 4:79
Neuromagnetic fields, neural origin of,
1:238239
Neuromagnetism, 1:242
Neuromuscular blocking drug, 1:29
Neuromuscular control, orthotics and, 6:80
Neuromuscular reeducation applications,
biofeedback and, 1:170
Neurons
axon guidance in, 1:414
pyramidal, 3:6364
Neuropeptides, quantitation of, 4:412
Neuroprosthetic applications, use of
peripheral nerve signals in, 3:125129
INDEX
Nickeltitanium (NiTi) shape memory
alloys, 1:2, 35. See also Nitinol
entries
medical devices using, 1:810
thermomechanical properties of,
1:45
Niosomal drug carriers, 2:473477
Niosome preparation
components used in, 2:474
methods of, 2:474475
Niosomes
in complex systems, 2:475
therapeutic applications of,
2:475477
toxicological aspects of, 2:475
55-Nitinol, physical and mechanical
properties of, 1:3t
Nitinol (NickelTitanium Naval Ordnance
Laboratory) alloy, 1:2, 313
Nitinol stents, 1:272
Nitric oxide therapy, 3:508
Nitrogen meter, 5:436
Nitrogen washout, 5:438
Nitroglycerine, 2:51
NM imaging, 5:108114. See also Nuclear
medicine (NM)
Noble metal electrodes, 1:126,
129131
Nociceptors, 6:437438
sensitization of, 6:439440
Noise
cancellation of, 1:234236
at electrode interface, 1:130
in exercise stress testing, 3:249250
in the scanning electron microscope,
4:483484
Noise levels, computer tomography,
6:575576
Noise reduction, using higher order
gradients, 1:235236
NOMOS Peacock System, 6:397398
Nonbonded pairs, in protein structure
prediction, 1:220221
Nonbyproduct radiation, materials codes
and regulations for, 2:171177
Nonbyproduct radionuclides, regulations
related to, 2:175177
Non-catheter/noninvasive angiography,
2:425426
Nonclinical laboratory studies, codes and
regulations related to, 2:143
Nonclinical studies, codes and regulations
for, 2:147
Noncontacting motion sensors, in neonatal
respiratory monitoring, 5:16
Nondispersible infrared gas analyzers,
5:436
Nonelectrophoretic-based DNA sequencing
methods, 2:433
Non-endoscopic procedures, 4:537538
Nonfluid-resistance pneumotachometers,
5:370371
Nonfocused radiation fields, 4:6364
Nonfusion treatment, for spine
stabilization, 3:585588
Nonhomogeneous obstructive lung disease,
3:507
659
660
INDEX
INDEX
Organizational information systems,
5:151152
Organizations, medical engineering,
4:311321
Organ motion, EPID use and, 4:96
Organs
elemental compositions of, 5:254t
local heating of, 1:190
tissue layers in, 6:180181
Organs at risk (OAR), 6:33
Organ synthesis, induced, 6:183
Organ weights, Wistar rat and human,
5:572t
Orthodontic arch wires, nickeltitanium
shape memory alloy, 1:8
Orthokeratology, contact lenses for, 2:327
Orthopaedic polymers, common properties
found in, 1:257t
Orthopedic applications
of nickeltitanium shape memory alloys,
1:910
of porous biomaterials, 5:402
Orthopedic braces, 6:231
Orthopedic devices, 5:187192. See also
Orthopedics
biocompatibility issues in, 5:191192
biomaterial surfaces of, 1:342343
design issues in, 5:190191
factors influencing, 5:188
materials issues in, 5:188190
Orthopedic implants, 1:255256
history of, 1:255
resorbable, 1:255256
Orthopedic materials, material properties
of, 1:304t
Orthopedic prostheses
materials in, 1:317320
titanium alloys in, 1:312
wear of, 1:315, 316
Orthopedics
cemented fixation in, 5:194
osseointegration in, 5:19419S
prosthesis fixation for, 5:192198
resorbable implants in, 1:255256
revolution in, 1:289290
Orthostatic hypotension, 1:16
Orthotic devices, 6:8085. See also
Orthotics
conventional, 6:8485
fabrication techniques for, 6:82f
lower limb, 6:88t
materials used in, 6:84
outcomes for, 6:92
performance criteria for, 6:8084
prefabricated and custom-fabricated
components in, 6:83f
spinal, 6:89t
upper limb, 6:89t
Orthotics, 6:8093
future of, 6:92
musculoskeletal evaluation and, 6:8592
uses of, 6:80
Orthovoltage units, for radiation therapy,
6:582
Orthovoltage X-ray units, requirements
for, 2:175t
Osborne pneumotachometer, 5:370
661
662
INDEX
INDEX
Peak velocity, in eye movements, 5:138
Pediatric cardiopulmonary resuscitation
(CPR), 2:5758
Pediatric emergency simulator (PediaSimECS), 1:46
Pediatric patients, EGG in, 3:94
Pedicle screws, 6:235
PEG Hemoglobin, clinical trial of, 1:520
Pelvic floor applications, biofeedback and,
1:170
Pelvic floor stimulation, 1:430
Pelvic nerve stimulation, 1:431
Penile plethysmograph, 6:159160
Penile prosthetics, for erectile dysfunction,
6:158159
Penile tumescence measurement,
6:156157
Pennes model, of bioheat transfer, 1:189
Penumbra, geometric, 2:131
Penumbra effect, pulse oximetry and, 5:212
People, as a hospital problem, 6:113114
Peptic ulcer disease, 3:388390
Peptide and protein immunoassay, for
microdialysis samples, 4:411412
Percentage depth dose (PDD), 2:130;
6:586589
Percutaneous coronary interventions,
evaluation of, 3:258
Percutaneous electrical nerve stimulation
(PENS), 3:27
Percutaneous extension hardware, 1:434
Percutaneous implants, 1:436438
Percutaneous neurostimulation testing
(PNE), 1:433434
Percutaneous transluminal angioplasty
(PTA), 1:615
Percutaneous transluminal coronary
angioplasty (PTCA), 1:601; 2:349
with stent placement, 4:542
Perflubron, 1:515
Perfluorochemical emulsions, as blood
substitutes, 1:513
Perfluorochemicals (PFCs)
clinical studies with, 1:515516
liquid ventilation with, 1:516
oxygen content of, 1:513514
Performance criteria
for gas systems, 3:380381
for vacuum systems, 3:383
Performance improvement, in a total
hospital safety program, 6:117
Performance maximization, 1:387
Performance optimization, 1:387388
Perfusion measures, in shock assessment,
6:167
Perfusion MR, 5:246
Perfusion ports, in anorectal manometry,
1:62
Pericellular matrix (PCM), 2:65
Perimeter effects, with metal electrodes,
1:146148
Perimetry, 6:529530
Periodontal ligament (PDL), 6:410,
413414
Periodontum, 6:413414
Periontogenic illness, as a hospital
problem, 6:114
663
664
INDEX
INDEX
Plating, in medical microbiology,
4:372375
Platinum electrodes, 1:129130
Platinum-iridium coil electrode, 1:151
Plethysmograph, penile, 6:159160
Plethysmographic blood pressure
measurement, 1:489
Plethysmography, 5:237241. See
Impedance plethysmography
air, 5:239
functional residual capacity by, 5:438
impedance, 5:238239
inductive, 4:131
magnetic susceptibility, 4:131
respiratory inductive, 5:378
strain gauge, 5:237238
Pleural pressure measurements,
6:520521
PLGA scaffolds, 1:379
PMT array, 1:5455, 56, 58. See also
Photomultiplier tubes (PMTs)
Pneumatic artificial heart, 3:457
Pneumatic ventilators, 6:506
Pneumatic ventricular assist devices,
3:451452
Pneumohydraulic pump, in anorectal
manometry, 1:62
Pneumolarynges, 4:231
Pneumotachography, in neonatal
monitoring, 5:14
Pneumotachometers, 5:367379. See also
Spirometers
calibration of, 5:372374
correction of, 5:376377
design specifications for, 5:377378
dynamic characteristics of, 5:374376
Fleish, 5:369
fluid-resistance, 5:369370
nonfluid-resistance, 5:370371
Osborne, 5:370
ultrasoundacoustic, 5:370
Pneumothoraces, upper airway, 3:507
pO2 electrode, 1:466
pO2 measurement, continuous
intraarterial, 5:212213. See also
Transcutaneous PO2 entries
pO2 sensors, optical, 5:169
POCO AXF 5Q synthetic graphite, 1:299
Point dose verification, 5:601
Point doses, optimal, 6:4344
Point of care devices, 1:23t
Point of care testing (POCT), 1:18, 2223
Point-of-gaze, measuring in the presence of
head motion, 3:273275
Point REsolved SpectroScopy (PRESS),
5:8081
Point-to-point video conferencing, 5:159
Poiseuille, Jean Louis Marie, 1:504
Poiseuilles law, 1:504
Poisoning, activated charcoal as antidote
for, 1:302
Poisson distribution, 6:245
Poissons ratio, of bone, 1:529
Poland, infrared imaging in, 6:353354
Polarization
electrode-electrolyte interface and,
1:125126
665
degenerate, 5:384
as a detection system, 5:384
DNA, 5:380381
length limitations in, 5:382383
mutations and, 5:382
nucleic acid amplification procedures
and, 5:385
real-time, 4:376377
sensitivity and contamination of,
5:381382
Polymer gels, 5:485486
MR imaging of, 5:486487
optical scanning of, 5:487488
ultrasound imaging of, 5:488
vibrational spectroscopic imaging of,
5:488
X-ray CT scanning of, 5:488
Polymer grafting, 1:347
Polymer/hydrogel molding, 1:413
Polymeric biomaterials, 1:329342
ASTM standards for, 1:334t
composition, structure, and properties
of, 1:331333
degradable, 1:279
evaluation of, 1:341
properties of, 1:334t
structures and trade names of, 1:333t
Polymeric drug delivery implants, 2:441
Polymeric drug delivery systems,
biodegradable, 2:504
Polymeric materials, 5:387392
as biomaterials, 1:105107
in biomedical engineering applications,
5:388391
chemical and physical properties of,
5:388
for drug delivery, 5:390391
used in tissue engineering, 5:388390
Polymeric particles, as drug carriers, 2:480
Polymeric scaffold fabrication techniques,
5:390
Polymerization, 1:330331
of dental resin composites, 1:323
Polymerization heat, of acrylic bone
cement, 1:543544
Polymer microfluidic devices, 4:425426
Polymer photolithography, 1:410411
Polymer powder-based tissue substitute
manufacture, 5:257
Polymers, 1:330
absorbable, 1:107
biodegradable synthetic, 1:339340
as biomaterials, 1:274278
biomedical applications of, 1:333341
in cardiovascular applications, 1:276
chemical structures of, 1:368369f
condensation, 1:330t
crystallinity of, 1:257258
in engineered tissue, 3:194196
medical uses of, 1:314
molecular weight of, 1:331
morphology of, 1:257
natural, 5:389390
resorbable, 1:257260
structure of, 1:257, 274, 275f
synthetic, 5:388389
for tissue engineering, 1:276
666
INDEX
INDEX
Pressurevolume relations, for arterial
elasticity, 1:89
Pressurized gas systems, 3:377381
Presurgical functional mapping,
1:244245
Preventive maintenance (PM), 3:223
Preventive maintenance interval,
selecting, 3:224225
Preventive maintenance procedures, 3:225
sample, 3:226f
Preventive maintenance program
effective, 3:224
evaluating, 3:225227
Preventive maintenance stickers, 3:228
Preview digital radiograph, 2:237
Primary disease, recurrence following liver
transplantation, 4:273
Primary graft nonfunction (PNF), after
liver transplantation, 4:271
Primary medical physics journals,
4:335336
Primary pathogens, 1:113114
Primary radiation barrier, 6:570
Principal Component Analysis (PCA),
1:241; 6:261
Privacy issues, related to augmentative
and alternative communication
systems, 2:210
Probability, 6:243244
relative frequency and, 6:243244
Probability density function (PDF), 1:71
for continuous variables, 6:244
Probability distributions, 6:244
characteristics of, 6:246
Probability mass function, 6:244
Probe configurations, in optical sensors,
5:162163
Probe cryosurgery technique, 2:366367
Probe geometry, in microdialysis sampling,
4:402403
Probe insertion trauma, in microdialysis
sampling, 4:408409
Probe/junction materials, in
thermocouples, 6:344
Probe materials, in microdialysis
sampling, 4:403404
Probe placement, in anorectal manometry,
1:63
Probes. See also Microdialysis probes
cytochemical, 2:390392
extrinsic, 4:497498
fiber-optic, 6:358359
fluorescent, 4:494498
genetic expressible, 4:498
intrinsic, 4:497
in nuclear medicine detectors, 5:95
organelle, 4:469470
solid-state, 1:63
thermistor, 6:333
Proctalgia, 1:68
Proctological diseases, cryosurgical
treatment of, 2:374375
Product development protocol, 2:146
Production condition optimization,
microbioreactors for, 4:393
Productivity, with Mount Sinai total
laboratory automation, 1:2627
667
668
INDEX
INDEX
Radiation barrier, primary, 6:570
Radiation beam, characteristics of,
2:127128
Radiation biology, 4:181
books/reports, 4:348349
Radiation byproduct material, medical use
of, 2:162166
Radiation codes/regulations, 2:153186
acronyms and definitions related to,
2:184185
for byproduct material, 2:158171
for nonbyproduct and machine-produced
radiation, 2:171177
for nonionizing radiation, 2:157158,
177184
organizations involved in, 2:153158
Radiation delivery, in three-dimensional
conformal radiotherapy, 6:3435
Radiation detectors, 5:506, 507, 518
solid-state, 5:514518
Radiation dose(s). See also Radiation
dosimetry
absorbed, 5:466467
in computed tomography, 2:244246
effects on cancer risk, 2:260
from screening CT, 2:260261
Radiation dose planning, computer-aided,
5:455463
Radiation dosimetry. See also Dosimetry;
Gel dosimetry; Radiation dose(s)
determining absorbed dose and air
kerma, 5:467471
measurement and quantities in,
5:465467
Monte Carlo techniques for, 5:471
for oncology, 5:465481
phantom materials in, 5:262
relative dosimetry and quality/
verification in, 5:476479
secondary dosimeter calibration,
5:474476
three-dimensional, 5:481500
Radiation exposure, effect of age at, 2:260
Radiation exposure limits, microwave and
radiofrequency, 2:183t
Radiation fields
focused, 4:65
nonfocused, 4:6364
Radiation heating, 3:468470
Radiation leakage, 6:564565
Radiation levels, scattered, 6:572573
Radiation measurements, books/reports
on, 4:348
Radiation oncology, imaging for,
6:3032
Radiation oncology physics books/reports,
4:338341
Radiation physics books/reports,
4:350351
Radiation-producing equipment,
nonmedical, 2:174175
Radiation protection, books/reports on,
4:346348
Radiation protection instrumentation,
5:500520
availability of, 5:501
choice of, 5:501503
669
670
INDEX
INDEX
orthotics in, 6:8093
virtual reality as a computer-generated
technology for, 6:74
Rehabilitation Engineering & Assistive
Technology Society of North America
(RESNA), 4:321
Rehabilitation exercises, 1:398
Rehabilitative biotelemetry microsystems,
1:424427
Rehau system, 4:579580
Reinforcement, of behavior,
1:166167
Relative biological effectiveness (RBE),
1:572; 6:3
Relative dosimetry measurements,
5:476479
Relative frequency, probability and,
6:243244
Relative power change, EGG, 3:90
Relaxation, biofeedback and, 1:178
Reliability, of electrophoresis, 3:140141
Remote afterloaders (RALs), 1:590. See
also High-dose-rate remote
afterloaders
high-dose-rate, 1:590594
Remote-control defibrillators, standards
for, 1:160161
Remote video-based eye tracking systems,
3:280283
Renal systems modeling, 5:318319
Repassivation, 1:310311
Repeat-fixation stereotactic radiotherapy,
5:491
Repetitions, exercise, 1:392, 399
Reporting
codes and regulations related to,
2:149150
human factors and, 3:541542
Resampling methods, 6:259261
Research, in murine cardiac ventricular
cells, 3:145146
Research and development, contraceptionrelated, 2:347348
Research-based software, for
communication disorders, 2:212
Reservoir bag, 1:33
in anesthesia delivery, 1:3031, 32
Reshaping cuff electrodes, 3:124125
Residual stress, of acrylic bone cement,
1:545546
Residual voltage output, in linear variable
differential transformers, 4:255
Resin-based composites (RBCs), 1:322;
6:9399
classification and physical properties of,
6:97t
clinical application of, 6:9798
fabrication of, 6:9395
phases in fabricating, 6:9495
physical and mechanical properties of,
6:9597
Resin composites, as dental fillings,
1:323324
Resin materials, prosthetic, 1:327. See also
Resins
Resin-modified glass ionomers (RMGIs),
1:324
671
672
INDEX
Rollators, 4:547548
Root-mean-square (rms) value, 3:107108
Rotary chair testing, vision-related, 5:139
Rotaterotate computed tomography,
2:231232
Rotational testing, vision-related, 5:139
Rotator cuff tendon, reconstruction of,
1:256
Roughening, of electrodes, 1:152153
Routine threshold audiometry, 1:94
Rubber bellows sensors, 1:175
Rubber electrodes, 1:148149
Rubber-like behavior, 1:1, 2
Rugby, wheelchair, 4:549550
Rule-based blood pressure controller,
1:496497
Saccades, 5:137139
Saccadic intrusions/oscillations, 5:140
Sacral nerve test stimulator, 1:433f
Sacral root stimulation, 1:431432
Sacrococcygeal teratoma, 4:172173
SafarElamKouwenhoven studies, 2:37
Safety. See also Hospital safety program
of anesthesia, 1:28
of biofeedback instrumentation, 1:168
in blood collection/processing, 1:456
contact lens, 2:325326
hyperbaric chamber facility, 4:27
medical gas analyzer, 4:334
systems perspective on, 6:110
for wheelchair users, 4:550552
Safety appliances, in electrosurgical units,
3:163164
Safety committee, hospital, 6:115
Safety features, in high-dose-rate remote
afterloaders, 1:594596
Safety monitors, anesthesia machine,
1:3940
Safety officer, in a total hospital safety
program, 6:116117
Safety systems, anesthesia machine,
1:3637
Sagittal laser, 5:530
Sagittal plane, scoliosis and, 6:122
Salt concentration, skin electrodes and,
1:135
SAM alignment tool, 1:222
Sample holder/stage, in near-field imaging,
4:438
Sample preparation, in neutron activation
analysis, 5:44
Samples. See also Sampling
paired/unpaired, 6:247248
in statistical methods, 6:240241
Sampling
in neutron activation analysis, 5:43
replacement in, 6:248
Sandwich electrode designs, 1:149
Sanger DNA sequencing method,
2:428431
Sanitation systems, as a hospital problem,
6:113
Saxtorph, M. H., 1:430
Scaffold fabrication
methods of, 3:196t
in tissue engineering, 3:196198
INDEX
Selection set, in augmentative and
alternative communication systems,
2:204205
Self-assembled monolayers (SAMs), 1:347,
410, 412; 4:388
Self-assembled nanoparticles, 5:34
Self-control conditions, of biofeedback
response, 1:178
Self-etch adhesives, 1:324
Self-heating
in thermistors, 6:321322
in thermistors, 6:357
Self-tuning regulator (STR), 1:492494
Semiautomatic blood pressure monitoring,
1:489
Semiclosed circle system, 1:3132
components of, 1:3233
Semiconductor diodes, 5:476
Semiconductor materials, used for
radiation detection, 5:516517
Semiconductor strain gages, 6:283284
Senographe full field digital
mammography systems, 4:304
Senoscan full field digital mammography
system, 4:304305
Sensitivity, in automated arrhythmia
analysis, 1:70
Sensitization, 6:439440
Sensor attachment, to microdialysis
probes, 4:411
Sensor design, in solid electrolyte cell
oxygen analyzers, 5:205
Sensorimotor rhythms, 1:243
Sensor materials, thermocouple, 6:344
Sensors. See also Optical sensors;
Piezoelectric sensors
in arterial tonometry, 6:403404
biomaterial surfaces of, 1:343
ECG, 1:175
glucose, 1:1617
heart rate, 1:175
respiration, 1:174175
SQUID, 1:231232, 233, 237, 238, 247
temperature, 1:170
Sensory assessment, for augmentative and
alternative communication systems,
2:207208
Sensory evoked potentials, 3:235236
Sensory testing, for anorectal manometry,
1:6463
Separation, in microbioreactors, 4:390391
Separation/detection methods,
electrophoresis with, 2:106107
Separation/purification microbioreactor
components, 4:390391
Separations-based methods, for
microdialysis sample quantitation,
4:409410
Sepsis, implant-contiguous, 1:117118
Septic shock, management of, 6:168
Sequence alignment methods. See also
Multiple sequence alignments
in bioinformatics, 1:217220
heuristic, 1:219
Sequential tomotherapy, 5:323
Serial tomotherapy, 6:397398
Serological assays, 4:375376
673
674
INDEX
INDEX
Software
in computer-based instrument systems,
2:314316
for computerized exercise feedback,
1:399400
DNA sequence analysis, 2:432t
medical image display, 5:355356
networking, 5:352353
phonocardiography, 5:289
sleep study, 6:220
statistical, 6:263264
text-to-speech, 1:446447
virtual simulation, 5:532
Solar simulators, 6:477478
Solar ultraviolet radiation, 6:476
Solgel-derived bioactive glasses,
1:287289
biological responses to, 1:293294
Solgel-derived bioactive glass foams,
1:292293
Solid ankle, cushion heel (SACH)
prosthetic foot, 4:552553
Solid conductive adhesive electrodes, 1:141
Solid electrolyte cell, oxygen analyzers,
5:204206
Solid gels, for electrodes, 1:141
Solid lipid nanoparticles (SLN), 2:484485
Solid phantom, 5:263264
Solids, surface energy of, 1:343
Solid-state detectors, 5:476477
Solid-state electrosurgical generators,
3:162163
Solid-state gas sensors, 4:332333
Solid-state probe, in anorectal manometry,
1:63
Solid-state radiation detectors, 5:514518
Solid tumors, treatment of, 4:606
Sols, 1:288
Soluble factor delivery, in tissue
engineering, 6:389
Solvent drying, nanoparticle fabrication
via, 5:3
Somatic afferent feedback, in control of
joint movement, 3:128
Somatosensory evoked fields (SEFs),
biomagnetic measurements and,
1:242243
Sonic Guide, 1:449450
Sound
as a hospital problem, 6:111
quantifying, 6:454
Sound analysis, 4:280281
Sound measurement, in neonatal
respiratory monitoring, 5:15
Sound transducers, 4:278279
Sound waves, 6:453454
Source lens, in the transmission electron
microscope, 4:481
Source lumen eccentricity, 1:610
Source stepping, 1:610611
Source-to-skin distance, in X-ray
equipment, 6:567
Space, as a hospital problem, 6:113
Spark gap oscillators, 3:161162
Spatial encoding, in magnetic resonance
imaging, 4:285286
Spatial filtering, 3:106
675
676
INDEX
INDEX
Stimulator case, in visual prostheses,
6:538539
Stimuli-responsive hydrogels, 5:391
Stimulus frequency otoacoustic emissions
(SFOAEs), 1:101
Stimulus, response and, 1:166, 167
Stimulus words, in audiology, 1:9697
Stokes, George Gabriel, 1:469
StokesAdamsMorgagni syndrome, 2:47
Stomach
effects of parenteral nutrition on, 5:130
electrophysiology of, 3:8485
Stone expulsion, improving, 4:264
Stone fragmentation
improving, 4:264
in lithotripsy, 4:260261
Stone localization, during lithotripsy,
4:260
Storage Access Networks (SAN), 5:350
Stow, Richard, 2:110f
Strain, relationship to stress, 6:282283
Strain energy equations, for arterial
elasticity, 1:88
Strain gage displacement sensors, in
neonatal respiratory monitoring, 5:16
Strain gages, 6:282290. See also Strain
gauge entries
applications for, 6:286288
signal preparation and amplification in,
6:285286
types of, 6:283285
Strain gauge, 4:578. See also Strain gage
entries
Strain Gauge measurement, 6:156157
Strain gauge plethysmography, 5:237238
Strain tensor, 1:88
Strand displacement amplification (SDA),
4:378
Strategic planning, hospital technology
changes and, 6:117
Stratum corneum, 1:131; 6:169
electrical properties of, 1:131132
Stress
biofeedback training and, 1:167168
relationship to strain, 6:282283
Stress concentrations, of bone, 1:531
Stress echo echocardiographic
examination, 3:1718
Stress electrocardiography, 3:4748
Stress induced martensite (SIM), 1:1, 4
Stress reduction, biofeedback clinical
outcome literature related to, 1:178
Stressstrain relations, for arterial walls,
1:8889
Stress testing
cardiopulmonary, 5:440441
of skin electrodes, 1:134
Stroke, 2:5253
biofeedback clinical outcome literature
related to, 1:182183
Stroke volume (SV), 2:12
Structural tissue, engineered,
3:203204
Structure identification, using a computed
tomography simulator, 2:270
Stylomandibular ligament, 6:417
Subatomic shear deformation, 1:1
677
678
INDEX
INDEX
Temperature-sensitive hydrogels, 5:391
Temperature sensors, 1:170
integrated-circuit, 4:157162
in neonatal respiratory monitoring,
5:1415
Temperature-to-frequency converters, in
temperature measurement
electronics, 6:328329
Temperature-to-time interval converters,
in temperature measurement
electronics, 6:328329
Template matching by CWA, 1:76
Template-based algorithms, in arrhythmia
analysis, 1:7476
Templates, in cellular patterning, 1:409
410
Temporal-spectral imaging, in peripheral
vascular noninvasive measurements,
5:247249
Temporary external pacemakers, 5:218
Temporary skin substitutes, 6:173175
ideal properties of, 6:173t
Temporomandibular joint (TMJ), 6:410,
415417
Temporomandibular (TM) ligament, 6:417
Tendons, 4:201, 245246
collagen in, 4:241242
components of, 4:241243
elastic fibers in, 4:242243
failure mechanisms of, 4:247248
fibermatrix interactions in, 4:243
measuring the properties of, 4:246247
properties of, 4:241252
proteoglycans in, 4:242
repair of, 4:248
Tennis, wheelchair, 4:550
TENS electrode system, 1:146, 148
Tensile behavior, of arterial walls, 1:87
Tensile modulus, of cartilage and
meniscus, 2:6667
Tensile properties, of cartilage and
meniscus, 2:6667
Tension
biofeedback clinical outcome literature
related to, 1:178179
biofeedback procedures for, 1:176178
biofeedback training and, 1:167168
Tension headache, biofeedback clinical
outcome literature related to,
1:178179
Tenth value layer (TVL), 6:592
Terahertz radiation, use in medical
diagnosis and therapy, 5:7071
Teratoma, sacrococcygeal, 4:172173
Tergitol TMN10, 1:291
Terminal arrythmia, 2:47
Terminal units (station inlets)
in gas systems, 3:380
for vacuum systems, 3:383
Tertiary structure, of proteins, 1:344
Testicular shield, 5:597
Testing
of heart valve prostheses, 3:430435
point of care, 1:2223
of tissue substitutes, 5:258262
Tetraethoxyl orthosilicate (TEOS), 1:292
Tetramethylsilane (TMS), 5:7778
679
680
INDEX
INDEX
Tomographic imaging, 6:559
Tomographic reconstruction, computers in,
5:114117
Tomography
electrical impedance, 6:361
fast X-ray computed, 5:246
optical coherence, 3:310311
phantom materials in, 5:266267
positron emission, 5:246247
quantitative computed, 1:553
for scoliosis, 6:127
Tomotherapy, 5:523; 6:395401
computed tomography simulation for,
2:274275
development of, 6:396397
helical, 6:398399
image guidance and adaptive
radiotherapy in, 6:401
serial, 6:397398
Tonometer sensors, design of, 6:404406
Tonometric blood pressure, measurements
accuracy of, 6:408
Tonometry, applanation, 5:236237. See
also Arterial tonometry
Tooth/jaw biomechanics, 6:410429. See
also Masticatory system
Tooth replacement modalities,
biomechanical properties of, 6:424427
Tooth restorations
extracoronal, 6:425
intracoronal, 6:424425
Top hat housing, for electrodes, 1:139
Topographical (3D) patterning methods,
1:413
Topography control, in microbioreactors,
4:388
Torsade de Pointes, 2:4647
Torsional eye movement, measurement of,
3:275
Torsion angles, in protein structure
prediction, 1:220
Total body water (TBW) resistance, in
dialysis patients, 1:212
Total disk replacement, 6:237
Total hospital safety program, 6:115117
Total internal reflection, in fiber optics,
3:302
Total internal reflection microscopy
(TIRM), 4:494
Total joint replacement, 2:73; 4:540541
Total laboratory automation, 1:24, 25f
Total lung capacity (TLC), 6:100
Total parenteral nutrition, comparing
methods of, 5:131132
Total parenteral nutrition regimen,
selecting, 5:132
Touch thresholds, 6:296
Toxicity, of whole-body hyperthermia, 4:51
Toxicological aspects of niosomes, 2:475
Toxicological profile, of cyclodextrins, 2:454
Toxicological testing, microbioreactors for,
4:393
Trabecular bone, 1:533534
Trabecular bone measurement, broadband
ultrasound attenuation in, 1:555
Trace element requirements, in parenteral
nutrition, 5:125t
681
682
INDEX
Tympanograms, 1:100101
Tympanometry, 1:100101
multifrequency, 1:101
Type I audiometer, 1:9293
Type I/II errors, 6:247
Type II audiometer, 1:93
Type IV audiometer, 1:93
Type A audiometer, 1:92
Type A tympanograms, 1:100101
Type B audiometer, 1:92
Type C audiometer, 1:92
Type E audiometer, 1:92
Type HF audiometer, 1:92
UBTL tests, 1:158, 159
UHMWPE-on-metal/ceramic hip joints,
3:518520
Ulceration, skin, 6:206207
Ultradeformable liposomes
formulative aspects of, 2:479
therapeutic potentialities of, 2:479480
Ultradeformable vesicular drug carriers,
2:479480
Ultra-density optical (UDO), 5:348
Ultrahigh molecular weight polyethylene
(UHMWPE), 1:274, 316317, 331,
333335. See also UHMWPE entries
as biomaterial, 1:106107
Ultrahigh molecular weight polyethylene
hip joints, 3:514, 515, 516
Ultrahigh vacuum instrumentation, in
surface analysis, 1:348, 349
Ultralow temperature isotropic (ULTI)
carbon, as a biomaterial, 1:273
Ultrasonic attenuation, 3:3
Ultrasonic devices, therapeutic
applications of, 1:190
Ultrasonic hyperthermia, 4:6286
medical applications of, 4:67
Ultrasonic imaging, 6:453473. See also
Acoustic imaging; Contrast imaging;
Ultrasound entries
array design in, 6:457458
bioeffects of, 6:471473
physical principles of, 6:453456
pulseecho method in, 6:455456
Ultrasonic transducers, radiation field of,
4:63
Ultrasonic wave propagating velocity (UV),
1:554
for bone measurement, 1:555
Ultrasonometry, quantitative,
1:553556
Ultrasound
in biotelemetry systems, 1:421422
clinical formats of, 3:23
during cryosurgery, 2:372
exposure to, 5:69
generation of, 4:63; 6:456459
high intensity focused, 6:365
interstitial, 4:3940
principles of, 3:35
propagation of, 4:63, 6667
signal processing, display, and
management in, 3:1013
temperature change estimation with,
6:361
INDEX
use in medical diagnosis and therapy,
5:71
versus electromagnetic radiation, 4:63
Ultrasound ablation, 6:365, 376
Ultrasoundacoustic pneumotachometers,
5:370
Ultrasound contrast agents, modern,
6:466, 467t
Ultrasound flow measurement techniques,
3:325327
Ultrasound-guided prostate seed implants,
5:424
Ultrasound imaging
during ablative treatment, 6:374f, 375
in peripheral vascular noninvasive
measurements, 5:245
of polymer gels, 5:488
Ultrasound physics books/reports, 4:345
346
Ultrasound propagation, in biological
tissues, 4:6667
Ultrasound scanners
B-mode in, 6:461
M-mode in, 6:461462
Ultrasound therapy devices, 3:473474
Ultrasound transducers, 6:456459
acoustic fields of, 6:458459
UltraStim Snap Electrodes, 1:149
Ultraviolet fibers, 3:303304
Ultraviolet phototherapy, 6:482
Ultraviolet radiation (UVR), 5:6566. See
also UV entries
biological effects of, 6:474476
diagnostic uses of, 6:480482
hazard assessment and protection
related to, 6:487488
measurement of, 6:478480
in medicine, 6:473490
skin disease therapy using, 6:482485
sources of, 6:476478
use in medical diagnosis and therapy,
5:70
Ultraviolet spectrum, 6:474
Ultraviolet therapy equipment, 6:484
Umbilical artery/vein catheterization
complications and risks associated with,
4:594595
indications and contra-lndications for,
4:589590
procedure for, 4:590
Umbilical artery/vein monitoring,
4:588597
anatomical and physiological aspects of,
4:589
historical aspects of, 4:589
Umbilical catheter, removal and
maintenance of, 4:595
Umbilical cord occlusion, bipolar, 4:179
Unalloyed titanium, as biomaterial, 1:105
Unconditioned response (UCR), 1:166
Unconditioned stimulus (UCS), 1:166
Uncooled thermal detectors, 6:349
Unfilled acrylic resins, 6:9394
Ungerleider electrode, 1:138
Uniaxial tensile behavior, of arterial walls,
1:87
Unidirectional valves, 1:33
683
684
INDEX
INDEX
Visual prostheses, 6:530549
advanced applications of, 6:546
approaches to developing, 6:534536
candidates for, 6:542543
chemical stimulation approach to
developing, 6:534
cortical approach to developing,
6:535536
engineering aspects of, 6:536542
ethical aspects of, 6:544545
evaluation of, 6:545
external components of, 6:536538
history of, 6:533
human and medical aspects of,
6:542545
hybrid approach to developing, 6:535
implanted components of, 6:538539
issues related to, 6:545546
limitations of, 6:545546
operation of, 6:539542
optic nerve approach to developing, 6:533
risks associated with, 6:543544
surgical methods for, 6:543
theory of operation of, 6:533534
transretinal approach to developing,
6:535
Visual system, basics of, 6:531532
Vital capacity (VC), 6:100
Vitallium, 1:271, 312
Vitamin D production, ultraviolet
radiation in, 6:487
Vitamin requirements, in parenteral
nutrition, 5:125t
Vitros 950 reaction slide, 1:20
Vocabulary selection, for augmentative
and alternative communication
systems, 2:209210
VOCARE bladder system, 1:432, 438441
Voice, after laryngectomy, 4:230
Voice command, in electronic aids to daily
living, 3:214
Voice prostheses, 4:231234
removable, 4:232
Volitional tasks, 1:386
Volta, Alessandro, 1:429
Voltage-based enhanced resolution
techniques, in electrophoresis, 3:137
138
Voltage-clamp technique, 3:142
Voltaic piles, 1:143
Volume conductance catheter, 1:206207
Volume currents, 1:238
Volume determination, model-based
relations for, 4:126127
Volume displacement respiratory flow
devices, 5:368369
Volume-displacement spirometers, 5:372
Volume flow measurement, 3:324329
Volumepressure curves, 6:517
Volume transducers, 5:435436
Volumetric heaters, 1:190
Volumetric oscillometry, 1:14
Volumetric pump drug infusion systems,
2:498499
Voluntary muscles, 1:385
von Bekesy, Georg, 1:93
Vortex shedding, 6:521
685
686
INDEX