CANCER BIOTHERAPY & RADIOPHARMACEUTICALS

Volume 15, Number 5, 2000

Mary Ann Liebert, Inc.

Benedict Cassen: The Father of Body Organ Imaging

William H. Blahd, M.D.
From the Imaging Service, Veterans Administration Greater Los Angeles Healthcare System and The
University of California at Los Angeles School of Medicine, Los Angeles, CA

SUMMATION

The invention ofthe radioisotope scanner by Benedict Cassen was seminal to the development ofbody organ
imaging. Cassen assembledthefirstautomatedscanningsystem in 1950. It was a motor-driven scintillation
detector coupled to a printer. The scanner was used to image the thyroid gland after the administration
ofradioiodine. Later, with the development oforgan-specific radiopharmaceuticals the scanner was widely
used during the late 50s until the early 70s to image the body organs.

The emergence of a comprehensive understanding
ofthe structure and function ofthe organ systems
of the human body stands as one of the most
important advances ofthe past millennium. Internal
imaging ofthe human body has been possible only
in the past century. Wilhelm Konrad Roentgen
using radioactive materials, led to the development
ofthe first imaging system that not only defined the
morphology of body organs but also revealed their
function. It was the seminal work of Cassen in
those early days that was the forerunner of what we
now know as radioisotope imaging. Cassen s work
'

( 1845-1923), a German physicist, discovered x-rays
in 1895, a discovery for which he received the first
Nobel Prize for Physics in 1901. Since then, it has
been the aim of imaging science to develop imaging
techniques to define the morphologic features and
functions ofthe internal organs. In the middle of
the 20* century, the work of Benedict Cassen, PhD,
Address reprint requests to WilliamH. Blahd, M.D., Nuclear
Medicine Section (115), VeteransAdministration Greater Los
Angeles Healthcare System, 11301 Wilshire Boulevard, Los
Angeles, CA 90073
predated other imaging systems, such as computed
tomography, magnetic resonance imaging, and
ultrasonography. Without doubt, Cassen's early
work was pivotal in the subsequent development
of these techniques.
Cassen was born November 13, 1902 in New
York City. His early life was fraught with tragedy,
separation from both parents, and insubstantial
means. At one point, he lived with an aunt in Lon-
don. She aided him financially enabling him to attend
the Royal College of Science. He graduated with
honors in Physics and Mathematics in 1927. He
returned to the United States to attend the California

423
Institute of Technology (Cal Tech) in Pasadena,
California, graduating with high honors and an M.S.
in Physics/Mathematics in 1928. In 1930, he
received his Ph.D. magna cum laude also in Phys-
ics/Mathematics from the same institution. He had
worked his way through Cal Tech as a teaching
fellow. Following graduation he won a stipend
from Princeton University as a National Research
Fellow that supported his physics research activities
for an additional two years.
Cassen left Cal Tech in the heart ofthe Depres-
sion with no job in sight. Fortunately, he was able
to find employment in New York as an X-ray
Physicist working for Westinghouse X-ray Corpora-
tion. He stayed only one year and then moved to
Harper Hospital in Detroit, Michigan where he
would continue to work as an X-ray Physicist for
six years. In 1939 he returned to Westinghouse to
work in their research laboratories until 1944, when
he again returned to Cal Tech to work on a war-
related project. After the war, he remained in
Pasadena two more years as a physicist at the U.S.
Naval Ordinance Test Station. In 1947 he joined
the United States Atomic Energy Commission
Project at the University of California at Los
Angeles (UCLA). Until his death in 1972, Cassen
worked as a Research Physicist at the UCLA
Laboratory of Nuclear Medicine and Radiation
Biology. He also attained the academic title of
Professor of Biophysics in the UCLA School of
Medicine. Cassen received many honors during his
career, including the first Distinguished Scientist
Award and, posthumously, the Nuclear Medicine
Pioneer Citation Award from the Society ofNuclear
Medicine.
CRYSTALS r
424
The genesis of his major work took place in the
late 1940s. Until 1949, the only counting device
available forthe detection of radioactivity was the
Geiger-Müller tube. The "Geiger tube" was ex-
tremely insensitive to high-energy radioactive
materials, such as radioiodine, responding to only
about 2% ofthe gamma rays emitted from a radio-
active source. Attempts were made in England and
in the United States in the late 1940s to focus the
Geiger tubes for the purpose of studying thyroid
function and morphology with radioactive iodine.
These efforts met with little success.
Since early in the 20th Century, the scintillation
effects (flashes of light caused when gamma rays
are absorbed by crystals of high density and trans-
parency) had been known. In fact, Rutherford and
coworkers had visually counted the individual
scintillations produced in zinc sulfite crystals by
alpha particles in their fundamental studies ofthe
nature of radioactivity. In 1947, Kallmann,1 in
Germany, devised a scintillation detector utilizing
organic crystals of naphthalene attached to the face
ofaphotomultipliertube. The photomultipliertube
was able to convert the flashes of light induced
the
by gamma rays striking crystals into ampli-
—
fied electrical signals. Kallmann's first detector
—
proved to be much more efficient in the detection
of gamma rays than the Geiger counter.
In 1949, Cassen and his coworkers Clifton
Reed, a biomédical engineer, and Lawrence Curtis,
a dedicated technologist, constructed the first
scintillation counter especially designed for the
localization ofradioiodine in the thyroid gland. The
counter was a directional scintillation detector
consisting of calcium tungstate crystals optically
ttmtt
Figure 1. Wide-angle Scintilla-
tion Detector. Calcium tungstate
crystals are cemented to the end-
window photomultipliertube (re-
printed with permission).
 Figure2. Dr.Herberte. Allen,Jr.,first
chief, Radioisotope Service, Veterans
Administration Center, Los Angeles,
manually performing a thyroid scan with
a prototype collimated scintillation
detector circa 1949.

coupled to the window of a photomultiplier tube.
This detector was 95 times more sensitive than a
Geiger tube. Furthermore, with a lead collimator
or sleeve, a resolution of about one-quarter of an
inch could be obtained. Figure 1 is a diagram of
the first "Directional Gamma Ray Detector" devel-
oped by Cassen.2
The excellent performance of this detector
immediately suggested biological and medical
applications. Initial tests demonstrated that rabbit
thyroid glands could be easily and rapidly located
after the administration of small doses of radio-
iodine. These results were in sharp contrast to those
obtained with Geiger tubes, which required doses
10 to 20 times greater.
Because the UCLA hospital and medical school
were not in operation at the time ofthese develop-
ments, a collaboration was developed with the
automatic motor-driven device that could scan the
thyroid with acceptable fidelity and in a reasonable
time (Figure 4). Basic components of the first
scanner were a dual motor-driven collimated
scintillation detector and an automated readout
system controlled by an electrical sealer. The idea
for the original scanner recording system, which
used a carbon paper strip printer or "pipper," was
appropriated by Cassen from the stock brokerage
dens where he often spent his lunch hours viewing
the ticker tape recorder that was a feature of every
brokerage'agency (Figure 5).
20
21
22
23

Radioisotope Service at the West Los Angeles 24

Veterans Administration Hospital. The opportunity ¿5

to explore the use ofthe scintillation detector was 2o

27
seized upon by Dr. Herbert Aller!, Jr., the first Chief
28
of the Radioisotope Service. One of the first
29
applications of the detector was an attempt to 30
delineate the morphology ofthe thyroid gland after
,

31
the administration of a dose ofradioiodine by point- 32

by-point counting ofthe gland using a plastic grid 33

that defined 400 coordinate counting positions3 MID I LINE

(Figure 2). Nearly two hours were required to

obtain a complete mapping of the thyroid gland
Figure 3. Grid Pattern of a Nontoxic Thyroid Adenoma.
(Figure 3). This procedure was so tedious and time- Note increased counts at left lower pole (reprinted with
consuming that efforts were immediately initiated permission). ,
to automate the procedure. Within a matter of
weeks, Cassen had conceived and developed an

425
Figure 4. (A) Schematic Design and (B) First
Model Cassen's Automated Radioisotope Scan-
of
ner (reprinted with permission).
Figure 5. Cassen and the First Automated Radioisotope
Scanner circa 1950 (scanner is in the Smithsonian Institution
National Museum of History and Technology, Washington,
DC).

The new scanner was taken to the West Los question, this was a defining moment in the evolu-
Angeles VA Hospital where the first in vivo thyroid tion of nuclear medicine and heralded the emerging
scan was performed in 1950 (Figure 6). Without clinical discipline.4'5

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¥26
 Recognizing the clinical potential ofthe scan-
ner, Cassen's assistants, Curtis and Reed, left their
employment at the UCLA Atomic Energy Project
and set out to manufacture thyroid scanners first
in Curtis' garage and later at a small plant in Playa
-

del Rey, California-this became the RC Scientific

Instrument Company. The first commercial thyroid
scanner was an adaptation of an over-the-bed

hospital tray (Figure 7). In the following years, the

scanner in a more sophisticated version was exten-

sively used in clinical studies ofthe thyroid gland

for the delineation of thyroid gland size as an aid
in radioiodine treatment of hyperthyroidism, in the
evaluation of thyroid nodules, and in the manage-
ment of thyroid cancer6 (Figure 8).
A major turning point in radioisotope scanning
took place in 1956 when Dr. David Kuhl (then a
resident in Radiology at the University of Pennsyl-
vania) and his colleagues developed a modification
ofthe Cassen scanner that substantially improved
its sensitivity and resolution7 (Figure 9). It used a
glow lamp as a variable light source that was
focused on an x-ray film in a light-proof box. The
glow lamp was activated by the scintillation detec-
tor output and moved in register with it. The
advantage of this system was its capability of
producing multiple shades of gray on x-ray film
concordant with the varying intensity ofthe light
from the glow lamp. This development, simply
known as a photoscanner, led to a vastly expanded
role for the radioisotope scanner. With the subse-
quent development of organ-specific'radiopharma-
ceuticals, photoscan images of major body organs,
e.g., brain, liver, kidneys and lungs, were readily
obtained (Figure 10).
With the advent of the radioisotope scanner
there resulted a rapid growth of clinical nuclear
medicine. Photoscanners were produced by multi-
ple manufacturers and were sold to hospitals and
clinics throughout the world (Figure 11). The
radioisotope scanner soon took its place as an
important contributor to the diagnostic process. The
development of the scanner reached its peak in
1973, when more than 2.5 million diagnostic
scanning procedures were performed8. In the late
1970s the radioisotope scanner ultimately gave way
to the scintillation camera that had been devised by
Cassen's friend and colleague, Hal Anger, at the
University California Donner Laboratory in Berke-
ley, California. The development ofthe radioiso-
tope scanner was a defining event in the

427
 Figure 9. Modified Cassen
Scanner with Photographie At-
tachment (reprinted with
permission).

Figure 11. Photoscanner circa 1958. Manufactured by

Picker X-ray Corporation.

Figure 10. Photoscan ofthe Brain of a Patient with Grade
III Astrocytoma. Note "doughnut sign."
evolution ofnuclear medicine and was the harbinger
ofthe emerging clinical discipline.
Benedict Cassen was one ofthose rare human
beings whose genius and creativity transcend their

428
 earthly times. His seminal contributions have had ABOUT THE AUTHOR
a major effect on our lives as practitioners of
medicine and on the health and welfare of our
patients. It is said that "The principal mark of
genius is not perfection but originality, the opening
of new frontiers" Arthur Koestler. Cassen opened
—

a new frontier, and it is appropriate that he take his

rightful place in the history and evolution of body

organ imaging.
REFERENCES

1. Kallmann H. Natur and Technik (July 1947).

2. Cassen B, Curtis L, Reed CW. A sensitive directional
gamma-ray detector. Nucleonics 1950;6:780.
3. Allen H, Libby R, Cassen B. The scintillation counter
in clinical studies of human thyroid physiology using
I-131. J Clin Endocrino! 1951 ; 11:492.
4. Cassen B, Curtis L. The in vivo delineation of thyroid
glands with an automatically scanning recorder. UCLA
Report 1951;130.
5. Cassen B, Curtis L, Reed C, et al. Instrumentation for
1-131 use in medical studies. Nucleonics 1951;9:46.
6. Bauer FK, Goodwin WE, Libby R, et al. Visual
delineation of thyroid glands in vivo. JLab Clin Med William H. Blahd, M.D. is Professor of Medicine
1952;39:153. at UCLA School of Medicine and Director of
7. Kühl DE, Chamberlain RH, Hale J, et al. A high- Nuclear Medicine Programs at the Veterans
contrast photographic recorder for scintillation counter Administration Greater Los Angeles Healthcare
scanning. Radiology 19561;66:730.
8. Maclntyre WJ, Harris CC. The decline and fall ofthe System. He had the privilege of knowing and
rectilinear scanner: Nuclear medicine instrumentation workingwith Benedict Cassen in his later years and
1970-1995. J Nucl Med Techno! 1995;23:16S. to observe much ofthe early radioisotope scanning
development. He has worked in thefieldofNuclear
Medicine for greater than 40 years and has been
involved in the further development ofradioisotope
NOTE: Figures used in this paper are reprinted
with permission by the editors and publishers of imaging technology and, more recently, in the
Seminars in Nuclear Medicine from an article development of positron emission tomography
entitled "Ben Cassen and the Development ofthe (PET). Dr. Blahd wrote one of the first nuclear
Rectilinear Scanner,"which appeared in Vol. XXVI, medicine textbooks that was used worldwide as a
No 3 (July), 1996, pg. 165-170. basic text. He continues to work as a clinician and
investigator.

429