Developing New Technology for Developing New Technology for

Local Tumor Control: Local Tumor Control:

A Bioengineering Approach A Bioengineering Approach
Andrew Wright MD Andrew Wright MD
Department of Surgery Department of Surgery
1/25/02 1/25/02
Background
Greater than one half of patients with Greater than one half of patients with
colorectal cancer will develop liver colorectal cancer will develop liver
metastases at some point in their clinical metastases at some point in their clinical
course course
Surgical resection of an isolated liver tumor Surgical resection of an isolated liver tumor
offers a five offers a five- -year survival between 25 and year survival between 25 and
38%, compared to a 0% five 38%, compared to a 0% five- -year survival year survival
without resection without resection
Background
Only 10 Only 1020% of patients with liver tumors 20% of patients with liver tumors
will have disease amenable to surgical will have disease amenable to surgical
resection due to high surgical risk or resection due to high surgical risk or
unfavorable anatomy unfavorable anatomy
Radiofrequency Ablation
High High- -frequency (460 kHz) alternating frequency (460 kHz) alternating
current flows from electrical probe through current flows from electrical probe through
tissue to ground tissue to ground
Probe
insertion
Extension of
prongs
RF current
application
Radiofrequency Ablation
12-prong Leveen probe, 4 cm
diameter (Radiotherapeutics)
Cool-Tip probe (17-gauge needle)
(Radionics)
9-prong Starburst probe, 5 cm diameter
(Rita Medical)
Radiofrequency Ablation
Bioheat Equation Bioheat Equation
Lesion Lesion << (Energy Applied x Local Tissue (Energy Applied x Local Tissue
Factors) Factors) Energy Lost Energy Lost
m
Q T T h T k
t
T
c + \ \ =

) (
bl bl
E J V
Temperature
Change
Thermal Conductivity
and heat constant
Current Density
*
Electric Field Constant
Heat loss through
blood flow
Finite Element Modeling
Determine material and electrical properties Determine material and electrical properties
of tissue and ablation system of tissue and ablation system
Develop geometric model Develop geometric model
Solve Bioheat equation Solve Bioheat equation
m
Q T T h T k
t
T
c + \ \ =

) (
bl bl
E J V
Finite Element Modeling
Bioengineering Approach
Define Problem Define Problem
Determine Possible Solutions Determine Possible Solutions
Model Model
Test Test
Refine Refine
Define Problem
Local recurrence as high as 30% Local recurrence as high as 30%
Uneven or irregular heating Uneven or irregular heating
Heat sink vessels Heat sink vessels
Several mms
RF
RF
Define Problem
Local recurrence as high as 30% Local recurrence as high as 30%
Uneven or irregular heating Uneven or irregular heating
Heat sink vessels Heat sink vessels
Difficult to treat large or multiple tumors Difficult to treat large or multiple tumors
Define Problem
Local recurrence as high as 30% Local recurrence as high as 30%
Uneven or irregular heating Uneven or irregular heating
Heat sink vessels Heat sink vessels
Difficult to treat large or multiple tumors Difficult to treat large or multiple tumors
Poor imaging and localization Poor imaging and localization
Ultrasound B-scan
Before
RF Ablation
Ultrasound B-scan
After
RF Ablation
Possible Approaches
Bioheat Equation Bioheat Equation
Lesion Lesion << (Energy Applied x Local Tissue (Energy Applied x Local Tissue
Factors) Factors) Energy Lost Energy Lost
m
Q T T h T k
t
T
c + \ \ =

) (
bl bl
E J V
Temperature
Change
Thermal Conductivity
and heat constant
Current Density
*
Electric Field Constant
Heat loss through
blood flow
Potential Solution #1
Bipolar RF Ablation Bipolar RF Ablation
Increase current density between Increase current density between
electrodes electrodes
Increase energy deposition Increase energy deposition
More uniform tissue heating More uniform tissue heating
Bipolar RF Ablation
Bipolar RF Ablation
FEM predicts nearly double lesion volume FEM predicts nearly double lesion volume
with bipolar electrode with bipolar electrode
Bipolar RF
In vivo porcine liver In vivo porcine liver
Monopolar Bipolar
Bipolar RF
Monopolar 3.93 Monopolar 3.93 ss 1.8 cm 1.8 cm
22
Bipolar 12.2 Bipolar 12.2 ss 3.0 cm 3.0 cm
22
3.93
12.2
0
2
4
6
8
10
12
14
16
18
20
1 Monopolar Bipolar
Bipolar RF
Bipolar RF
Monopolar, d=2.3 mm
Bipolar asymmetric,
d=1.8 mm
Bipolar symmetric,
d=1.0 mm
Bipolar RF
Problems Problems
Inability to control two Inability to control two
electrodes electrodes
independently independently
Difficult technical Difficult technical
placement placement
Unable to treat Unable to treat
multiple tumors multiple tumors
Potential Solution #2
Multiple Probe RF Ablation Multiple Probe RF Ablation
Allows overlapping treatment of large Allows overlapping treatment of large
solitary tumors solitary tumors
Allows simultaneous treatment of Allows simultaneous treatment of
multiple tumors multiple tumors
Multiple Probe RF Ablation
Monopolar Bipolar
Disadvantage: Disadvantage:
electrical shielding electrical shielding
between electrodes between electrodes
(Faraday cage) (Faraday cage)
Multiple Probe RF Ablation
Block diagram of system
Multiple Probe RF Ablation
Monopolar Bipolar Alternating Monopolar
Multiple Probe RF Ablation
Prototype Multiple Probe Device Prototype Multiple Probe Device
Computer controlled electromechanical switch Computer controlled electromechanical switch
Multiple Probe RF Ablation
Ex Vivo Ex Vivo Testing Testing
Multiple Probe RF Ablation
In Vivo In Vivo Testing Testing
Multiple Probe RF Ablation
Single Probe Ablation Simultaneous Multiple
Probe Ablation
Multiple Probe RF Ablation
In Vivo In Vivo Testing Testing
Lesion Volume Lesion Volume
Single 10.7 cm Single 10.7 cm
33
Dual 17.3 cm Dual 17.3 cm
33
(per lesion) (per lesion)
Time to Target Temperature Time to Target Temperature
Single 2.7 minutes Single 2.7 minutes
Dual 3.4 minutes Dual 3.4 minutes
Multiple Probe RF Ablation
Change to electrical switch Change to electrical switch
Increase number of probes Increase number of probes
Increase speed of switching Increase speed of switching
Decrease load on generator Decrease load on generator
Evaluate synergism of overlapping multiple Evaluate synergism of overlapping multiple
probe RF ablations probe RF ablations
Potential Solution #3
Bioheat Equation Bioheat Equation
Lesion Lesion << (Energy Applied x Local Tissue (Energy Applied x Local Tissue
Factors) Factors) Energy Lost Energy Lost
Tissue Impedance (resistivity) Tissue Impedance (resistivity)
Tumor Resistivity
Electrical properties of normal liver and Electrical properties of normal liver and
tumor tumor (K12/TRb) (K12/TRb) measured measured in an in vivo rat in an in vivo rat
liver liver model model
Tumor vs. Normal Liver Tissue
0
200
400
600
800
1000
1 10 100 1000 10000 100000 1000000
Frequency (Hz)
R
e
s
i
s
t
i
v
i
t
y

(
;

c
m
)
Tumor loc 1
Tumor loc 1, orthog.
Tumor loc 2
Tumor rat, norm. tissue
Normal rat, 26.10.
Normal rat, 4.10.
Tumor Resistivity
Finite Element Model Finite Element Model
Tumor diameter = 2 cm
Tumor Resistivity
Current Density Current Density
500 kHz 100Hz
Tumor Resistivity
Temperature Temperature
500 kHz 100Hz
Tumor Resistivity
Lesion Difference Lesion Difference
Gray circle represents
tumor boundary
Tumor Resistivity
Human? Human?
Colorectal metastasis to liver Colorectal metastasis to liver
Tissue Resistivity
0
500
1000
1500
2000
2500
10 100 1000 10000 100000 1E+06
Frequency (Hz)
R
e
s
i
s
t
a
n
c
e

(
o
h
m
)
Normal Surface
Tumor Center
Tumor Surface
Alternative Solution
Microwave Ablation Microwave Ablation
Theoretical advantages over Theoretical advantages over
radiofrequency ablation radiofrequency ablation
No ground pad No ground pad
Not limited by tissue charring and Not limited by tissue charring and
impedance changes impedance changes
Use of Multiple Probes Use of Multiple Probes
Microwave Ablation
Larger zone of active heating Larger zone of active heating
1-2 cm
MW
1-2 mm
MW
Microwave Ablation
MW
RF
Multiple Probe Ablation
Null Hypothesis Null Hypothesis
Because microwave and radiofrequency Because microwave and radiofrequency
ablation are both heat based, there will be ablation are both heat based, there will be
no difference in ablation size or lesion no difference in ablation size or lesion
pathology between the two technologies pathology between the two technologies
Methods
Microwave Ablation Microwave Ablation
Vivant Medical prototype system Vivant Medical prototype system
10 minute ablation, 40 Watts 10 minute ablation, 40 Watts
Radiofrequency Ablation Radiofrequency Ablation
RITA Medical Systems Starburst RITA Medical Systems Starburst
10 minute ablation, 3cm deployment 10 minute ablation, 3cm deployment
100 100
oo
C target temperature C target temperature
Microwave Ablation System
Vivant Medical
13g, 15cm dipole antenna
915MHz generator
Fiberoptic temperature monitor
Radiofrequency Ablation System
RITA Medical
14g, 15cm expandable array
460 kHz generator
Integrated thermocouple
Lesion Volume
Lesion Volume
0
5
10
15
20
25
0 2 28
Day
V
o
l
u
m
e

(
c
m
3
)
MW
RF
*
*
* p=.02
Lesion Length
Lesion Length
0
2
4
6
8
10
0 2 28
Day
L
e
n
g
t
h

(
c
m
)
MW
RF
*
*

* p<.001
p=.02
p<.001

Lesion Diameter
Lesion Diameter
0
1
2
3
4
5
0 2 28
Days
H
e
i
g
h
t

(
c
m
)
MW
RF
Pathology
RFA
MW
Immediate 48
o
4 weeks
Laboratory Data
Platelet Count
0
100
200
300
400
500
600
700
0 5 10 15 20 25 30
Days
P
l
a
t
e
l
e
t

C
o
u
n
t

(
K
/
u
L
)
MW
RF
*
* p<0.001
No significant difference in AST, ALT, No significant difference in AST, ALT,
LDH, Alkaline Phosphatase, WBC, or HCT LDH, Alkaline Phosphatase, WBC, or HCT
CT Imaging
48 Hours 4 Weeks
Microwave Ablation
Pathological and radiologic characteristics Pathological and radiologic characteristics
similar between RF and MW ablation similar between RF and MW ablation
MW lesions larger than RF MW lesions larger than RF
MW ablation technically easier than MW ablation technically easier than
multiple multiple- -prong RF ablation prong RF ablation
Multiple Probe Microwave Ablation
Hypothesis Hypothesis
Multiple probe hepatic ablation will Multiple probe hepatic ablation will
result in synergistically larger lesion sizes result in synergistically larger lesion sizes
by shielding lesion center from blood by shielding lesion center from blood- -
flow mediated cooling flow mediated cooling
Methods
Microwave Protocol Microwave Protocol
Domestic Swine Domestic Swine
10 minute ablation, 40 Watts 10 minute ablation, 40 Watts
Single Probe Ablation Single Probe Ablation
Multiple Probe Ablation Multiple Probe Ablation
3 parallel probes in triangular array 3 parallel probes in triangular array
Separation between probes varied Separation between probes varied
from 0.5 to 3.5cm from 0.5 to 3.5cm
Methods
Microwave Protocol Microwave Protocol
Single Probe Multiple Probe
Assessment
Lesion dimensions calculated Lesion dimensions calculated
Multiple Probe lesions scored for shape Multiple Probe lesions scored for shape
Score Score Criteria Criteria
11 Discontinuous Discontinuous
22 >25% Deflection >25% Deflection
33 10 10- -25% Deflection 25% Deflection
44 <10% Deflection <10% Deflection
55 Round Round
Results
Results
Lesion Diameter
0
1
2
3
4
5
6
Single Probe Multiple Probe
p<0.001
D
i
a
m
e
t
e
r

(
c
m
)
Results
Lesion Diameter
0.0
1.0
2.0
3.0
4.0
5.0
6.0
Single Probe Multiple Probe
p<0.001
D
i
m
e
n
s
i
o
n

(
c
m
)
Lesion Volume
0
10
20
30
40
50
60
70
Single Probe Multiple Probe
p<0.001
V
o
l
u
m
e

(
c
m
3
)
Results
Size by Separation Size by Separation
Lesion Volume by Measured Probe Separation
0
10
20
30
40
50
60
70
80
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Average Probe Spacing (cm)
r=0.24, p=0.43
V
o
l
u
m
e

(
c
m
3
)
Results
Lesion Shape Lesion Shape
Lesion Shape by Measured Probe Separation
0
1
2
3
4
5
6
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Probe Separation (cm)
r=-0.75, p=0.003
S
h
a
p
e
Results
Lesion Shape Lesion Shape
Results
Results
5 Probes 5 Probes
Microwave Ablation
Microwave ablation has several theoretical Microwave ablation has several theoretical
advantages over RF ablation advantages over RF ablation
Multiple probe microwave ablation may Multiple probe microwave ablation may
allow for treatment of larger, more complex allow for treatment of larger, more complex
tumors as well as simultaneous treatment of tumors as well as simultaneous treatment of
multiple tumors multiple tumors
Multiple probe ablation may improve Multiple probe ablation may improve
treatment of tumors near blood vessels treatment of tumors near blood vessels
Microwave Ablation
Phase I Clinical Study Phase I Clinical Study
Improved imaging
Physical characteristics of tissue change Physical characteristics of tissue change
with ablation with ablation
z

2
c
z
z
2
c
z T
1 2
0 0
(
=

'
+

'

'
+

'

RF echo-signal after a 1
0
C Temperature Increase
Base Line RF echo-signal
2
X
1
X z ( n
X ........
0
c
Initial Speed of Sound
K
Tissue Dependent
Parameter
Improved Imaging
Ultrasound B-scan
Before
RF Ablation
Thermal Image
After
2 Minutes
Thermal Image
After
10 seconds
Improved Imaging
Ultrasound B-scan
Before
RF Ablation
Ultrasound B-scan
After
RF Ablation
Softer Region
(Normal Tissue)
Elastogram
Showing The
Thermal Lesion
Stiffer Region
(Thermal Lesion)
Future Directions
Further development and clinical testing Further development and clinical testing
Multiple Probe RF Multiple Probe RF
Variable Variable- -frequency RF frequency RF
Microwave Ablation Microwave Ablation
Elastography and Thermal Monitoring Elastography and Thermal Monitoring
Future Directions
Modify local tissue factors Modify local tissue factors
Tumor Tumor- -specific ablation sensitizers specific ablation sensitizers
Adjuvant or neo Adjuvant or neo- -adjuvant chemotherapy adjuvant chemotherapy
Alternative Technologies Alternative Technologies
Biomolecular Engineering Biomolecular Engineering
Confocal Microwave Confocal Microwave
??
Acknowledgments
David Mahvi MD David Mahvi MD
Fred Lee MD Fred Lee MD
John Webster PhD John Webster PhD
Dieter Haemmerich Dieter Haemmerich
PhD PhD
Tomy Varghese PhD Tomy Varghese PhD
Tyler Staelin MD Tyler Staelin MD
Chris Johnson Chris Johnson
Vivant Medical Vivant Medical
http//rf-ablation.engr.wisc.edu