Intravascular brachytherapy physics: Report of the AAPM Radiation
Therapy Committee Task Group No. 60
Ravinder Natha)
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510
Howard Amols
Department of Radiation Oncology, Columbia University, New York, New York 10032
Charles Coffey and Dennis Duggan
Department of Radiation Oncology, Vanderbilt Medical Center, Nashville, Tennessee 37232
Shirish Jani
Division of Radiation Oncology, Scripps Clinic and Research Foundation, La Jolla, California 92037
Zuofeng Li
Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610
Michael Schell
Department of Radiology Oncology, University of Rochester Cancer Center, Rochester, New York 14642
Christopher Soares
National Institute of Standards and Technology, Gaithersburg, Maryland 20899
James Whiting
Department of Medical Physics and Imaging, Cedars-Sinai Medical Center, Los Angeles, California 90048
Patricia E. Cole
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510
Ian Crocker
The Emory Clinic, Atlanta, Georgia 30322
Robert Schwartz
Cardiovascular Department, The Mayo Clinic, Rochester, Minnesota 55905
~Received 21 January 1998; accepted for publication 25 November 1998!
Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose
range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an
angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American
Association of Physicists in Medicine ~AAPM! formed a task group to investigate these issues and
to report the current state of the art of intravascular brachytherapy physics. The report of this task
group is presented here. © 1999 American Association of Physicists in Medicine.
@S0094-2405~99!01302-4#
Key words: intravascular brachytherapy, angioplasty, restenosis, dosimetry, radiation protection
TABLE OF CONTENTS
I. INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . .
II. CLINICAL BACKGROUND AND RATIONALE
.............................................
A. Overview of coronary anatomy. . . . . . . . . . . . . .
B. Atherosclerosis and restenosis. . . . . . . . . . . . . . .
C. Percutaneous transluminal angioplasty. . . . . . . .
D. Overview of the restenosis problem. . . . . . . . . .
E. Preclinical studies of vascular irradiation. . . . . .
F. Clinical studies of vascular irradiation. . . . . . . .
1. Peripheral vessels. . . . . . . . . . . . . . . . . . . . . .
2. Coronary vessels. . . . . . . . . . . . . . . . . . . . . . .
III. IRRADIATION TECHNIQUES. . . . . . . . . . . . . . .
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IV. OVERVIEW OF BASIC PERCUTANEOUS
TRANSLUMINAL CORONARY
ANGIOPLASTY ~PTCA! PROCEDURES AND
DEVICES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
V. DOSIMETRY STUDIES OF INTRAVASCULAR
BRACHYTHERAPY. . . . . . . . . . . . . . . . . . . . . . . .
A. Dosimetry studies of gamma emitting seeds
and wires. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
B. Dosimetry studies of beta emitting seeds and
wires. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
C. Dose inhomogeneity due to noncentering of
source. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
D. Comparison of depth dose from gamma and
beta rays. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
0094-2405/99/26„2…/119/34/$15.00
© 1999 Am. Assoc. Phys. Med.
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Nath et al.: Intravascular brachytherapy physics
E. Dosimetry studies of permanent radioactive
stents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
F. Dosimetry studies of radioactive liquid filled
balloon catheter. . . . . . . . . . . . . . . . . . . . . . . . . .
VI. RECOMMENDATIONS FOR
INTRAVASCULAR BRACHYTHERAPY
PHYSICS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
A. Dose specification and renormalization for
catheter-based intravascular brachytherapy
systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Catheter-based intravascular brachytherapy
for peripheral vessels using gamma emitter..
2. Catheter-based intravascular brachytherapy
for coronary vessels using gamma emitters..
3. Catheter-based intravascular brachytherapy
using beta emitter. . . . . . . . . . . . . . . . . . . . . .
4. Recommendations on dose prescription for
a catheter-based system. . . . . . . . . . . . . . . . .
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I. INTRODUCTION
Coronary artery disease is the leading cause of morbidity and
mortality in the western world.1 Approximately 450 000 angioplasties are performed annually in the USA. Although
major complications from angioplasty occur in only 1%–2%
of patients, angiographically diagnosed restenosis occurs in
35%–40% of patients.2 Restenosis is the major limitation of
angioplasty. The impact of restenosis is highlighted by studies that compared coronary angioplasty to bypass surgery as
a treatment strategy for coronary artery disease. Patients
treated by angioplasty had lower initial costs and fewer major complications, but at a six month to three year follow-up
these patients had more angina, required more revascularization procedures, and most of the cost benefit of angioplasty
was lost because of restenosis.3 Coronary stent placement in
conjunction with angioplasty can reduce the restenosis rate
to 22%–32%.4,5 The cost of restenosis has been estimated to
be $4000–$7000 in direct costs for the first episode of restenosis. The societal cost of restenosis in the United States of
America is estimated between 800 and 2000 million dollars
per year.2 Recent preclinical studies indicate that irradiation
using ionizing radiations in the dose range of 15–30 Gy may
reduce substantially the problem of restenosis in patients
who have undergone an angioplasty. Using intravascular
brachytherapy, radiation doses in this range can be delivered
with minimal normal tissue toxicity because of the high localization of dose to the immediate vicinity of radioactive
sources in brachytherapy. It is estimated that the restenosis
rate may drop from roughly 35%–40% to well below 10% if
radiation is delivered to the obstruction site during or after
angioplasty.6 Therefore, the potential of intravascular
brachytherapy in reducing restenosis has aroused a tremendous interest in the cardiology community.
Dosimetry at distances of the order of a millimeter from
radioactive sources is poorly known. In traditional brachytherapy the dose is typically specified at 1 cm from the
source and effects of low-energy photons and secondary
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B. Dosimetric characterization of catheter-based
intravascular brachytherapy systems. . . . . . . . . .
1. Dosimetry of catheter-based gamma
emitters. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2. Dosimetry of catheter-based beta emitters. .
3. Recommendations on dose calibration of
catheter-based system. . . . . . . . . . . . . . . . . . .
C. Dosimetric characterization of radioactive
stents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
D. Recommendation of clinical prescription and
dose reporting of radioactive stents. . . . . . . . . . .
E. Quality assurance and safety aspects. . . . . . . . . .
VII. SUMMARY OF RECOMMENDATIONS. . . . . .
VIII. FUTURE CONSIDERATIONS. . . . . . . . . . . . . .
ACKNOWLEDGMENTS. . . . . . . . . . . . . . . . . . . . . . .
APPENDIX: CORONARY AND PERIPHERAL
VASCULAR INTERVENTIONS GLOSSARY. . . . .
electrons are essentially ignored. In intravascular brachytherapy, however, the entire lesion may be 1–3 mm in thickness. To understand the results of various preclinical studies
using a variety of radionuclides and delivery systems, it is
essential to determine the dosimetry in the millimeter range.
A better understanding of dosimetry in the millimeter range
will help in the development of optimum clinical devices and
their efficacious use in different institutions using different
radionuclides and devices.
In late 1995 the American Association of Physicists in
Medicine ~AAPM! formed a task group to investigate these
issues and report the current state of the art of intravascular
brachytherapy physics. The specific charge to the task group
included the following:
~1! To review the physical, radiobiological, and clinical rationale of using intravascular brachytherapy.
~2! To review the currently proposed irradiation techniques:
~a! intravascular gamma radiation ~e.g., 192Ir) brachytherapy;
~b! intravascular beta radiation ~e.g., 33P) brachytherapy.
~3! To review the literature for types and applications of
various interventional probes, including specifically the
use of intra-arterial stents.
~4! To review the interventional diagnostic imaging procedures including intravascular ultrasound used in evaluation and treatment planning for brachytherapy.
~5! To recommend a dose prescription site ~or region! for
selected intravascular brachytherapy procedures ~e.g., 1
mm depth from the arterial lumen surface or 2 mm from
the center of the lumen, etc.!.
~6! To recommend calibration and dosimetry procedures
~relative and/or absolute! for the determination of dose
distributions around intravascular brachytherapy applicators, including beta-emitting stents.
~7! To recommend a quality assurance procedure, including
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radiation safety, for the safe and efficacious application
of intravascular brachytherapy.
Here we present the recommendations of the AAPM on
the physics of this novel application of radiation in the treatment of cardiovascular disease.
II. CLINICAL BACKGROUND AND RATIONALE
A. Overview of coronary anatomy
The arteries conduct blood from the heart to the capillary
bed in the heart muscle. The arterial system begins in large
blood vessels close to the heart. The largest, the aorta, carriers the full volume of blood expelled and is approximately
2–3 cm in diameter. The division of this and subsequent
major branches leads to a continuous increase in their number and spread, with a progressive decrease in their diameter.
The coronary arteries are a branching system of mildly to
severely tortuous vessels lying on the outer surface of the
heart. Two main coronary arteries, the left and right coronary
arteries ~LCA and RCA!, originate from the aortic root, just
outside the aortic valve. The branching of these main arteries, and the regions of the heart they serve, vary considerably
among individuals, although there are some general patterns
~Fig. 1!. The RCA, which serves the inferior wall of the left
ventricle and portions of the right ventricle, has few branches
in the proximal half of its length. The LCA bifurcates within
a few centimeters of its origin into the left anterior descending ~LAD! and left circumflex ~LCX! arteries, both of which
give rise to many tertiary branches.
Normal proximal coronary arteries range from 3–5 mm
diam at their origin and taper slowly throughout their length,
except at major bifurcations, where the sum of the branch
cross-sectional areas is approximately equal to the area
proximal to the bifurcation. Angioplasty is rarely performed
in arteries with a normal diameter less than about 1.5 mm,
and, at present, stents are rarely placed in arteries whose
normal diameter is smaller than about 3.0 mm, as measured
by angiography.
Arteries consist of a tubelike structure that is lined by
endothelium ~Fig. 2!. Next to the endothelial layer is a subendothelial connective tissue layer called the intima, which
has surface cells flattened and longitudinally oriented. Intima
is surrounded by an elastic layer called the internal elastic
membrane. Surrounding these inner layers is a relatively
thick layer of media composed of smooth muscle cells and
elastic tissues in varying proportions. The outer layer of the
media is called the external elastic membrane. The outermost
layer of arteries is the adventitia, composed mainly of collagenous fiber. The principal difference between arteries of
different sizes is found in the media. In larger vessels elastic
tissue predominates, while in the smaller vessels smooth
muscle cells form most of the substance.
B. Atherosclerosis and restenosis
Atherosclerosis is the formation of plaques that gradually
reduce the lumen of the artery, compromising blood flow and
oxygen delivery. The plaque begins in the intima by deposits
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of fatty debris from blood. Smooth muscle cells from the
internal elastic membrane and media proliferate. Collagen
and elastin are produced and accumulate in the intima, leading to focal thickening where platelets and cholesterol soon
begin to adhere to the endothelium ~Fig. 2!. As the disease
progresses, lipids accumulate in the intima to form yellow
fatty streaks. A fibrous plaque then begins to form. It contains lipids, necrotic cells, and collagen. The media becomes
thickened from this process. Eventually, a complex lesion
develops as the core of the fibrous atherosclerotic plaque
necroses, calcifies, and hemorrhages. This causes reduction
in blood flow, platelet aggregation, and ultimately formation
of a thrombosis with consequent myocardial ischemia and/or
infarction.
Restenosis after an angioplasty follows a similar history.7
Angioplasty leads to a fracture of the atherosclerotic plaque,
the intima, and sometimes extending into the media ~Fig. 2!.
These injury sites are immediately lined by platelets and later
lined by a fibrin meshwork in which platelets and red blood
cells become entrapped. This thrombus usually stabilizes
over the course of minutes to hours. Within several days
blood borne monocytes initiate the phagocytosis of the fibrin
meshwork. Simultaneously smooth muscle cells migrate
from the media into the intimal subendothelial space, leading
to neointimal proliferation. Over weeks to months the neointima becomes less cellular and the healing site begins to
resemble a fibrous plaque. In most patients the lumenenlarging effect of angioplasty outweighs the lumennarrowing effect of neointimal hyperplasia. However, in
about 40% of the patients neointimal hyperplasia is excessive and results in clinically symptomatic restenosis within
three to six months.
Since the 1950s the gold standard for the diagnosis of
coronary atherosclerosis has been the angiogram. The utility
of the angiogram derives from its ability to determine easily
the distribution of coronary arteries and the location of atherosclerotic narrowings. However, the angiogram is not able
to image the atherosclerotic plaque itself. The development
of intravascular ultrasound ~IVUS! has led to a new tool
capable of imaging the distribution of plaque, the calcium
deposits in the plaque, and the placement of the stent.8–11 A
typical example of IVUS images is illustrated in Fig. 3 from
a recent review by Yock et al.12 Such cross-sectional views
of the vessel anatomy have proven useful in treatment planning of intravascular brachytherapy.
C. Percutaneous transluminal angioplasty
The primary objective of angioplasty is to re-establish a
stable lumen with a diameter similar to that of the normal
artery. This goal may be achieved using a variety of interventional devices, including the angioplasty balloon, laser,
rotoblator, and stent, all described briefly below. The selection of one or more interventional devices for a given
stenotic lesion depends on the size, location, and characteristics of the lesion. A brief review of these devices is presented now.
Balloons: in cases where the lesion can be spanned with
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an angioplasty balloon, a sufficient increase in diameter
~‘‘acute gain’’! can often be achieved by balloon dilatation
alone. The mechanism by which balloon angioplasty increases lumen diameter is by stretching and usually rupturing
the internal elastic lamina, often resulting in one or more
fissures extending into the medial layer. Flaps may protrude
into the lumen, and/or a dissection may extend well beyond
the angioplasty site. These common post-angiographic morphologies increase the risk of thrombosis and abrupt occlusion. In addition to this source of acute failure, the most
important problem is restenosis.
Cutting and ablating devices: while balloon angioplasty
enlarges the lumen by stretching and splitting the wall, in
some cases this is made impossible by lesions with a lumen
too small for the balloon to cross, or by heavy calcification
of the arterial wall, making it too tough and inelastic to split
or stretch. In these cases it may be necessary to remove
tissue by cutting ~atherectomy device!, abrading ~rotoblator!,
or vaporizing ~laser!. Because the risk of arterial wall perforation is clearly much higher with these methods, they are
usually not applied aggressively to achieve the desired final
lumen size; rather, they are used to initially ‘‘debulk’’ the
lesion, and then followed by balloon angioplasty and/or stent
placement.
Stents: placement of one or more intra-arterial stents following angioplasty effectively repairs dissections, prevents
flaps from protruding into the lumen, resists elastic recoil,
and minimizes loss of lumen diameter due to remodelling,
significantly improving the short term result of angioplasty.
For this reason stents are being placed in an increasing fraction of angioplasty procedures. However, stents do not appear to eliminate restenosis and, in fact, may actually stimulate proliferation. For this reason there is a strong interest in
finding a method, such as radiation therapy, that can be used
in conjunction with stenting to produce a definitive intervention for obstructive atherosclerotic lesions.
D. Overview of the restenosis problem
Restenosis is a complex process comprising three separate
mechanisms: early recoil, neointimal hyperplasia, and late
contraction ~Fig. 4!.13 Chronologically, the first is the elastic
recoil that occurs promptly after the overstretch of the artery.
This has been quantitated at approximately 50% of the crosssectional area or one-third the lumen diameter on average. In
other words, an artery dilated with a 3 mm balloon will commonly have a lumen in the dilated segment of 2 mm following balloon deflation and passage of a few minutes time. This
elastic recoil does not seem to progress much beyond the
first few minutes after balloon deflation. Observations made
the day following balloon angioplasty show little further decrease in lumen size. The second component of restenosis is
intimal proliferation resulting in new tissue growth occupying the cracks and tears in the vessel wall and sometimes
growing to produce very severe reobstruction of the artery.
This process probably begins within days after angioplasty
and continues for weeks or months. The third mechanism for
restenosis that has been recently elucidated is analogous to
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wound contracture and is sometimes called remodeling. The
entire artery may become contracted so that the external elastic lamina occupies a smaller circumference than it did following the procedure. It has been estimated by Mintz14 that
this process may account for up to 60%–65% of the lumen
loss judged by intravascular ultrasound.
Although the focus of the discussion above has been coronary arteries, similar problems of restenosis following angioplasty or stent placement have been encountered within the
peripheral vascular system. Several institutions report fiveyear patency rates following femoropopliteal balloon angioplasty of 50%–61%. Recent studies of stents in femoropopliteal vessels demonstrated a similarly high rate of
restenosis as with balloon angioplasty.15–19 This phenomenon seems less frequent in stented iliac and renal arteries.
The incidence of restenosis in peripheral vessels seems
highly dependent on the anatomic location of the original
lesion, the morphology of the lesion, and the distal flow with
lower restenosis rates occurring in larger vessels, and focal
lesions with good distal flow.
E. Preclinical studies of vascular irradiation
The potential role of radiation in preventing restenosis
following angioplasty or stent placement was first elaborated
in the literature by Dawson,20 although there exists clinical
and preclinical studies antedating this publication. The first
author to report the use of endovascular brachytherapy was
Friedman and his group21 from the Mount Zion Hospital in
San Francisco, who in the mid 1960s showed that the formation of vascular plaques could be inhibited by inserting an
192
Ir wire into the aorta and delivering approximately 14.4
Gy to the vessel wall. It remained until the early 1990s when
several investigators reported mixed results using external
beam radiotherapy.22–28
Interest in intravascular brachytherapy grew recently
when groups led by Weinberger from Columbia, Waksman
from Emory, and Raizner from Baylor reported a potential
benefit of intraluminal 192Ir in the prevention of restenosis in
the porcine model. In the Columbia and Emory studies the
radiation was administered with a hand delivered 192Ir ribbon
~Best Industries, Springfield, VA!. Raizner delivered the
dose in their study with a high dose rate afterloader ~Omnitron, Houston, TX!. Comparing their results is confounded
by differences in source configuration and prescription
points, and methods of analysis. Weinberger29–31 found that
15 and 20 Gy delivered at a 1.5 mm distance from the source
center significantly reduced neointimal hyperplasia, but 10
Gy was worse than controls. In contrast, Waksman et al.32,33
showed that doses in the range of 3.5–14 Gy delivered at a 2
mm distance from the source center ~0.5 mm depth from a
typical arterial wall! significantly reduced neointima formation compared to controls with the animals being sacrificed
at two weeks following injury. Here 14 Gy was associated
with the greatest reduction in neointima formation and 7 Gy
when administered 48 h following balloon injury was more
effective than when delivered at the time of injury. Mazur34
examined the potential benefit of 10, 15, and 25 Gy delivered
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123
FIG. 2. Schematic drawing of the three stages of atherosclerotic lesion formation. ~reprinted with permission from ‘‘Mouse models of atherosclerosis,’’ by Jan L. Breslow, in Science Vol. 272, May 3, 1996, p. 686. Copyright 1996, American Association for the Advancement of Science.!
FIG. 1. Coronary ~cardiac! circulation. Anterior view of arterial distribution.
~from Principles of Anatomy and Physiology, 4th ed., by Gerard J. Tortora
and Nicholas L.P. Anagnostakos. Copyright© 1984 by Biological Sciences
Textbooks, Inc., A & P Textbooks, Inc. and Elia-Sparta, Inc. Reprinted by
permission of Addison-Wesley Educational Publishers.!
at 1.5 mm depth and found that 15 and 25 Gy were effective,
but no benefit was seen with 10 Gy. Both Waksman and
Weinberger subsequently extended these observations to six
months and showed the durability of this effect. In these
studies Waksman et al. showed the benefit of delivering 7
and 14 Gy at 2 mm depth and Weinberger’s group showed a
durable effect with 20 Gy at 1.5 mm depth at six months.
Two groups reported on preclinical studies utilizing beta
sources developed specifically for clinical use. Verin35,36 has
shown in a hypercholesterolemic rabbit restenosis model that
radiation delivered with a 90Y wire would reduce neointimal
hyperplasia. In their study doses of 6, 12, and 18 Gy were
delivered at the intimal surface immediately following balloon angioplasty and the animals were sacrificed six weeks
later. Although BUdR labeling was reduced at eight days
with 6, 12, and 18 Gy, only the 18 Gy group showed a
significant reduction of neointima formation at the six-week
period. Waksman et al.37 reported two studies with a ribbon
of 90Sr/Y seeds. When used following balloon angioplasty in
the porcine model of restenosis, there was a significant reduction in neointimal hyperplasia with doses of 7, 14, 28,
and 56 Gy delivered to a 2 mm distance from the center of
the source. There was evidence of a dose response curve
with maximal reduction in neointima seen at 28 Gy. When
they compared their results obtained with the beta source and
192
Ir there was no difference between them in terms of efficacy. The treatment times and radiation exposures to animals
and personnel were significantly reduced with the beta
source. A second publication from this group also showed
that radiation delivered prior to stent implantation with either
192
Ir or 90Sr/Y was effective in reducing neointimal hyperplasia compared with stents alone.
Two groups reported using radioactive stents as a means
of preventing restenosis. Hehrlein38 was the first to demonstrate that a regular metallic stent ~Palmaz–Schatz! made
Medical Physics, Vol. 26, No. 2, February 1999
radioactive in a cyclotron could reduce restenosis when applied to rabbit iliac vessels. A stepwise reduction of neointimal hyperplasia was seen with stent activities between 3.9
and 35 mCi. Although there was evidence of delayed reendothelialization, no increase in vascular thrombosis was
seen. Laird et al.39 has reported that neointimal hyperplasia
could be inhibited in the short term by the application of a
32
P impregnated stent. These stents had activities in the range
of 0.14 mCi and delivered doses to tissue of approximately
280 cGy ~a more detailed analysis of dosimetry is discussed
later in Sec. VII C and Table VI!. When assessed at 28 days
post-implantation, there was a significant reduction in neointimal proliferation and stenosis with the radioactive stents.
There would seem to be some advantage to the 32P impregnated stent over the radioactive steel stent due to the long
half-life of some of the decay products of the steel stent.
Sources with activities described by these authors could be
handled without significant radiation precautions unlike the
catheter-based systems.
F. Clinical studies of vascular irradiation
1. Peripheral vessels
The first study done using radiation to prevent restenosis
was carried out by Liermann, Schopohl, and Bottcher in
Frankfurt.40,41 In this study they selected patients for treatment who had a clinically relevant recurrent stenosis in the
superficial femoral artery greater than 4 cm in length that had
occurred less than six months after the last percutaneous
transluminal angioplasty ~PTA!. All the patients had undergone prior PTA or laser therapy and had a stent placed prior
to or at the time of irradiation, and all patients were 65 years
or older. The patients received 12 Gy at the lumenal surface
with a HDR afterloader. With 25 patients treated as of their
latest follow-up report and some patients with over five years
of follow-up, they have not seen any evidence of restenosis
in the treated segment. Not all of the patients have undergone
systematic reevaluation with angiography so there is no information published or presented at this time as to any degree of lumenal narrowing following treatment. One would
have generally expected at least a 30% restenosis rate in
these size vessels following primary angioplasty, and this
study provides strong evidence for the benefit of adjuvant
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irradiation. What is more important, however, is the fact that
there was no late restenosis or other evidence of complications of the adjuvant irradiation. The authors point out in
their paper that the source was not centered within the peripheral vessel, and if the catheter had remained opposed to
one of the coronary arteries for the duration of the treatment
it is possible that the absorbed dose, based on minimum and
maximum distances of the vessel wall, ranged from 8–28
Gy. This information gives us some indication that the dose
range of effective treatment and safety could be quite broad.
The second clinical study of irradiation in peripheral vessels was also carried out in Germany by Steidle42 and his
colleagues in Ravensburg. This study was a randomized
study between stent placement with and without adjuvant,
fractionated external radiation treatment. The patients were
treated with 12.5 Gy in 2.5 Gy fractions following stent
placement in superficial femoral arteries. Of the 11 patients
who received radiation treatment, there were only two episodes of occlusion with minimum seven months follow-up.
In the 13 control patients there were five episodes of occlusion. Furthermore, there were no complications attributable
to the radiation.
The only additional study carried out in peripheral vessels
in humans is a preliminary report from Waksman et al.43
involving adjuvant irradiation following angioplasty at the
venous anastamotic stenosis in percutaneous grafts in dialysis patients. Stenosis at the venous anastamosis of the polytetrafluoroethylene ~PTFE! graft with the outflow vein is the
most common ~680%! underlying cause of graft failure. Patency rates after recanalization with thrombolysis and angiolasty are plagued by recurrent restenosis: six months patency
rates are only 30%–45%. In the 11 patients ~16 lesions!
treated at Emory with radiation following angioplasty, only
36% of the grafts remained patent at 44 weeks. This pilot
study was too small to determine effectiveness of radiation
and did not use a centering catheter for the wire, a probable
requirement for dose optimization.
A randomized multicenter trial for intravascular brachytherapy of femoral popliteal arteries has been initiated by
Waksman. This protocol is approved by the USFDA. In this
protocol the irradiated group will receive 14 Gy to a depth of
2 mm from the vessel wall. The intent is to deliver this dose
to the adventitia using a centered catheter-based beta source.
Nori et al. have initiated a phase I/II FDA approved pilot
study using external beam irradiation therapy following angioplasty of venous outflow stenosis in failing grafts.
2. Coronary vessels
The first study of intracoronary brachytherapy in humans
was initiated in July 1994 by Condado and his colleagues in
Caracas, Venezuela.44 This study involved the administration
of radiation from the insertion of a special small diameter
192
Ir wire ~1.5 Ci! into the vessel after angioplasty, rotoblator, or stent placement. In this study 22 arteries in 21 patients
were treated over a five-month period of time. At the initiation of their study, the patients received 25 Gy at a standard
depth of 1.5 mm from the source center. After the first ten
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FIG. 3. Intravascular ultrasound images of a minimal and a moderate plaque
in a coronary artery. ~Reprinted, with permission, from ‘‘Intravascular ultrasound,’’ by P. Yock, P. Fitzgerald, and R. Popp, Sci. Am. Sci. Med.
~Sept./Oct. 1995, p. 68!.
arteries were treated, a further 12 arteries were treated with
all but one of these patients receiving 20 Gy at the lumenal
surface of the reference diameter. With a minimum of six
months follow-up in the treatment groups there have been
four cases of restenosis. Angioplasty was successful in 20 of
22 lesions. The delivery of radioactive source wire was successful to all treated sites and was free of major procedural
complications. Angiographic study at 24 h post-procedure
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FIG. 4. Components of restenosis: early recoil, neointima formation, and late
contraction. ~reprinted from ‘‘Restenosis following angioplasty’’ in Vascular Brachytherapy, edited by R. Waksman, S. B. King, I. R. Crocker, and R.
F. Mould, 1996, with permission from Spencer B. King, III, author.!
demonstrated a reduction of the mean minimal lumen diameter ~MLD! from 1.960.6 mm to 1.460.3 mm. At 60 days,
angiography demonstrated total occlusion in two arteries and
a pseudoaneurysm in one artery. At late follow-up all remaining arteries ~20! remained patent with a mean MLD of
1.760.8 mm. Angiographic restenosis was demonstrated in
four patients. Clinical events included myocardial infarction
in one patient, a repeat of percutaneous transiuminal coronary angioplasty ~PTCA! in four, and persistent angina in
seven patients. None of the four restenosis cases occurred in
the initial group treated with 25 Gy. What is more interesting
in this study is the fact that there were some vessels that got
slightly larger after treatment, suggesting positive remodeling.
The second clinical trial that has been presented is the
randomized trial of endovascular irradiation using a hand
delivered 192Ir source train organized by Teirstein et al. at
The Scripps Clinic in La Jolla, CA.45 In this trial patients are
randomized to receive or not receive endovascular irradiation
following intracoronary stent placement. In this study the
prescribed dose is based on intravascular ultrasound ~IVUS!
assessment of the maximum distance from the catheter to the
coronary stent. Here 8 Gy is delivered to this point as long as
the maximum dose does not exceed 30 Gy. Fifty five patients
were enrolled: 26 were assigned to the 192Ir group and 29 to
the placebo group. Restenosis occurred in 17% of the patients in the 192Ir group versus 54% of those in the placebo
group. What is more important about this trial is the fact that
they have managed to use a hand-delivered iridium source of
up to ;140 mCi without seeing any increase in badge readings of the participating physicians. Furthermore, they have
left the radiation source within the coronary artery for up to
one-half hour without any increase in complications from
this procedure. Results of this randomized trial indicate that
radiotherapy and stenting significantly reduced subsequent
restenosis in patients with previous restenosis; restenosis was
decreased by angiographic, ultrasonographic, and clinical
measurements; and no adverse events were observed at about
12 months. The investigators conclude that radiotherapy with
192
Ir reduces the proliferative response to human coronary
angioplasty.
Intraluminal beta irradiation has been shown by Popowski
et al.46 to markedly decrease fibrointimal proliferation after
PTCA. Between June 21 and November 15, 1995, 15 patients ~six women and nine men, age 7265 years! underwent
intracoronary beta irradiation immediately after a conventional PTCA procedure. Both the PTCA and irradiation proMedical Physics, Vol. 26, No. 2, February 1999
125
cedure were done in a conventional catheterization laboratory, using an endoluminally centered pure metallic 90Y
source, a newly developed technique of intracoronary beta
irradiation. Both the PTCA and the irradiation procedure
were technically feasible in all attempted cases, and a dose of
18 Gy was delivered, with a local exposure time of 400
6200 s ~the range 153–768 s!. In four patients the intervention was completed by intra-arterial stent implantation because of dissection induced by the initial PTCA. These early
experiences of Popowski et al. suggest that reliable and reproducible dose delivery can be achieved, and that coronary
endoluminally centered beta brachytherapy is both feasible
and safe on a short-term basis in the clinical setting.
King et al.47 initiated a feasibility trial using a catheter
system based on a 90Sr/90Y beta source. At present, 23 patients have undergone balloon angioplasty followed by endovascular irradiation. The 30-day safety endpoint examination
has been completed without any adverse events being noted,
and the patients are being followed with angiographic examinations at six months to document the degree of neointimal
formation, the late lumen loss and loss index, the restenosis
rate, and any other effects that might be observed angiographically. Although there is no control group for this
study, the patients were selected by the criteria of the Lovastatin™ restenosis trial and the quantitative angiographic
assessment is being performed by the same core laboratory
that performed that trial. Early results from this feasibility
study are also highly encouraging.
Early clinical trials with 32P stent activities of 0.5–3.0
m Ci have shown no untoward events at 1 month
follow-up.48 Presently, clinical dose escalation safety studies
using 32P Palmaz–Schatz stents are underway in the USA
and Europe; additionally planned randomized clinical trials
are forthcoming.
III. IRRADIATION TECHNIQUES
Intravascular brachytherapy techniques fall naturally into
two categories: ~1! temporary implant-balloon angioplasty
~radioactive seed or wire! and ~2! permanent implantradioactive stent. For temporary implants, single fraction,
acute doses of 15–20 Gy are required to a length of 2–3 cm
of the vessel wall, which may be 2–5 mm in diameter. The
dose distribution should be confined to the region of the
angioplasty, with reduced doses to normal vessels and the
myocardia. Dose rates greater than 5 Gy/min would be optimal in order to maintain treatment times within tolerable
limits, although precise requirements are not yet known. Depending on catheter design, the patient will have greatly reduced arterial blood flow during irradiation, and longer treatment times will increase the risk of complications. This
suggests high dose rate ~HDR! afterloading, perhaps with
specially designed sources suitable for insertion into standard
or modified catheters.
Current angiographic techniques utilize open ended catheters flexible enough to negotiate multiple bends between the
femoral and coronary arteries, yet stiff enough to be pushed
through greater than 100 cm of the artery. Vessels suitable
126
Nath et al.: Intravascular brachytherapy physics
for intravascular brachytherapy may be as small as 3 mm
diam and small radii of curvature need be navigated. The
radioactive source must have similar flexibility. Source integrity is of great importance as dislodgment into a coronary
artery could be fatal. Seeds should have dimensions on the
order of less than or equal to 1 mm diam and 1–10 mm
length. Treatment with such a source would require either
multiple sources on a line ~such as those currently available
for conventional afterloading!, or programmable source
placement ~similar to conventional HDR units! to permit
treatment of 2–3 cm of coronary artery wall, or up to 5 cm of
the vessel wall in peripheral vessels. In theory, the source
could be inserted directly into the coronary artery, or, more
likely, into a conventional or slightly modified balloon catheter. In either case, it is desirable that the source be centered
within the coronary artery to ensure uniform dose to the arterial walls. Balloon catheters designed to ensure some centering have recently been developed by some manufacturers.
The objective of intravascular brachytherapy is to irradiate a lesion with a size of millimeters in contrast to conventional brachytherapy, where the lesion may be 1–5 cm in
size. This makes it possible to consider low-energy photon
emitters and beta emitters as potential sources for intravascular brachytherapy. For conventional interstitial brachytherapy procedures such as those for prostate cancer photon
energies as low as of 20–30 keV are considered adequate.
However, for conventional intracavitary brachytherapy, such
as those for gynecological cancers, it is necessary to use a
minimum photon energy of about 50 keV in order to obtain
adequate depth of penetration.49 For the same reason, i.e., the
inadequate depth of penetration in tissue, the beta emitters
are generally not suitable for conventional brachytherapy.
Nath and Liu50 explored this issue of intravascular brachytherapy by calculating radial dose functions of a range of
energies for photons and electrons in the range of 1–10 mm
using Monte Carlo simulation. Calculated radial dose functions for photons and electrons in a point source geometry
are shown in Fig. 5. The reference depth was chosen to be 2
mm. It was concluded that photons above an energy of 20
keV and electrons above an energy of 1.0 MeV are acceptable from the point of view of an adequate depth of penetration for intravascular brachytherapy.
Many different radionuclides51 are under investigation for
intravascular brachytherapy ~Table I!. Most intravascular
brachytherapy studies to date have used 192Ir seeds of 10–20
mCi activity. Typical seed dimensions are 0.5 mm diam, 3
mm in length. Multiple seed arrays embedded in a 1 mm
diam plastic catheter are used with variable spacing but usually less than or equal to 0.5 cm. While these sources have
proven useful for preliminary studies, the relatively highenergy and low dose rates are not ideal. In addition, to
achieve the dose rates of 4–5 Gy/m, approximately 500–
1000 mCi of gamma emitting isotopes will be required. This
will present additional radiation safety problems, with either
HDR or hand loaded sources. Lower-energy gamma and
x-ray emitters such as 125I and 103Pd also present fewer radiation safety problems, but are not currently available at the
required specific activities.
Medical Physics, Vol. 26, No. 2, February 1999
126
32
P, 90Sr, 90Y, and other beta emitters have been suggested. Beta emitters would require much lower total activities ~20–50 mCi! and have additional, obvious radiation
safety advantages. Electrons from some common beta emitters, however, may not have sufficient range for treating
larger diameter peripheral vessels.
An alternative possibility for irradiation is to inject a betaemitting liquid directly into the angioplasty balloon. This
may have advantages over other proposed procedures in that
accurate source positioning and uniform dose to the vessel
walls is assured, and it can be used in conjunction with existing catheters. About 370 MBq ~equal to 10 mCi! of 32P in
a 0.2 ml balloon would be required to deliver 20 Gy at a
distance of 2 mm from the center. The chemical and radiological toxicity must also be acceptable, in the event of balloon rupture ~the probability of balloon rupture is less than
0.001!. Several high-energy beta-minus emitters ~and possibly positron emitters! appear to be possible for this application.
Beta-minus emitters, such as 32P and 90Y also appear to be
most suitable for use with permanently implanted radioactive
stents, although low-energy x-ray emitters such as 125I and
103
Pd may also be possible. The radioactive material can be
coated onto, or impregnated into, the actual stent using ion
implantation techniques. Activation of the stent in a nuclear
reactor is also possible. The advantages of radioactive stent
implantation include conformity of dose to the lesion and
very low activities ~mCi!.
For any of these techniques, cost and half-life will be
factors in source selection. If the amortized cost of the radioactive source is greater than $103 – $104 per patient, the
treatment may not be economically viable. A high demand
for these treatments, however, can reduce substantially the
cost per patient. The remote-controlled afterloaders may
have a higher capital cost but lower operational cost compared to radioactive stents.
IV. OVERVIEW OF BASIC PERCUTANEOUS
TRANSLUMINAL CORONARY ANGIOPLASTY
„PTCA… PROCEDURES AND DEVICES
Reliable systems have evolved for establishing arterial access, controlling bleeding, and maneuvering catheters and
catheter-based devices through the arterial tree to the treatment site. Systems for peripheral and coronary arteries are
similar, but the smaller size and greater tortuosity of the
coronaries require smaller and more flexible devices. Detailed descriptions of these systems exist in textbooks as well
as in device manufacturers’ literature. Here we present an
overview of typical systems for coronary angiography, balloon angioplasty, atherectomy, laser, and stent placement,
with a particular emphasis on standard dimensions and other
physical requirements that apply to all intraarterial devices.
A list of stent types is presented in Table II.
Patients are selected for PTCA on the basis of a variety of
invasive and noninvasive tests, including ECG, echocardiogram, nuclear stress test, and/or cardiac catheterization. The
final decision and planning of the PTCA procedure is always
127
Nath et al.: Intravascular brachytherapy physics
based on information from the coronary angiogram, which
provides the best definition of coronary anatomy, location,
and severity of lesions, and the presence of collateral vessels
to regions of myocardium supplied by diseased vessels being
considered for PTCA ~‘‘target lesions’’!. In many cases this
diagnostic coronary angiogram is performed immediately
prior to the angioplasty procedure, significantly reducing the
cost and risk compared to two separate procedures.
Because angioplasty and/or stenting is frequently performed as an acute therapy, it is common for patients to be
unstable, requiring close monitoring and possible interventions such as intravenous medications, defibrillation, or
placement of an intraaortic balloon pump. Patients must be
closely attended by the coronary angiography team at all
times during the procedure.
Arterial access: patients scheduled for angiography
and/or angioplasty are usually placed on medications that
include aspirin, a calcium channel blocker, and antianginal
medication. In the catheterization laboratory, the patient is
placed on the table, covered with sterile drapes, and the potential entry sites are prepared. An intravenous line is established for the administration of fluids and drugs, and the
patient is usually placed on conscious sedation. The target
artery is accessed transluminally via a puncture of an access
artery, typically the common femoral artery or the brachial
artery. After administering a local anesthetic the access artery is entered percutaneously with an 18 or 19 gauge hypodermic needle or a micropuncture set, a guide wire is passed
through the needle into the artery, and the needle is removed,
leaving the wire in place. An introducer sheath is passed over
the wire and pushed through the puncture site into the artery,
forming a tight seal with the puncture opening. A guide catheter is then inserted through the introducer and into the artery, forming a tight seal with the introducer. Hemostasis is
completed by a rotating hemostatic valve on the Y adaptor at
the proximal end of the guide catheter.
Introducer sheath and maximum size of interventional devices: the use of an introducer sheath reduces arterial trauma,
particularly during interventional procedures that involve
multiple exchanges of catheters and guide wires. Damage to
the artery and subsequent complications are directly related
to introducer sheath size, which is expressed as the diameter
of the largest catheter that can be passed through it, typically
7 or 8 French (1 French51/p 50.318 mm diam). This size
places an upper limit on the diameter of all angioplasty catheters of less than 2 mm, since these devices must pass
through the guide catheter that must itself pass through the
introducer sheath. In practice, angioplasty devices must be
much smaller than this limit in order to pass through target
lesions with minimum lumen diameters typically less than 1
mm. Devices that are deployed following balloon dilatation,
such as stent delivery systems or intravascular brachytherapy
sources, can be slightly larger than 1 mm, but systems approaching the limit set by the introducer sheath/guide catheter size will fail to negotiate many coronary arteries, even
after angioplasty.
Guide catheter: guide catheters and diagnostic angiography catheters have preformed bends at the distal end to faMedical Physics, Vol. 26, No. 2, February 1999
127
cilitate selective entry into the left or right coronary arteries.
A relatively stiff guide wire keeps the catheter straight while
it is advanced up the descending aorta ~femoral approach!,
around the aortic arch and down the ascending aorta. The
wire is then withdrawn, allowing the catheter to take the
proper shape for entering the ostium of the target coronary
artery. Contrast material is injected to visualize the artery for
diagnosis or to confirm a previous angiogram, to verify the
adequate placement of the guiding catheter, and to assess the
size and topography of the target lesion and arterial branches.
Guide wire: when angioplasty is to be performed, the angioplasty device ~e.g., balloon, laser, rotoblator, or stent delivery catheter! and its flexible intracoronary guide wire are
inserted into the guiding catheter via the ‘‘thru-port’’ of the
Y adaptor and advanced to the ostium. At this point the
steerable guide wire alone is advanced under fluoroscopic
guidance up to, across, and as far as possible past the target
lesion to provide a stable guide for repeatedly advancing the
angioplasty catheter across the lesion. The guide wire is necessary because balloon and other intracoronary catheters
generally lack the torquability and steerability necessary to
navigate through a tortuous and/or branching arterial tree.
Even if intracoronary catheters had these properties, interventional procedures frequently require that catheters be
placed across the lesion and withdrawn multiple times, so
that a guide wire over which these catheters can be quickly
and safely advanced saves time.
A wide variety of guide wires for various situations and
from various manufacturers is available. The distal 20–30
cm are typically radiopaque, and the distal tip may be formable by the operator to help negotiate a particular artery, or
have a permanently bent segment ~‘‘J’’ tip! to facilitate steering. Standard short guide wires are at least 175 cm long.
Long guide wires, or exchange wires ~see below!, are 300 cm
long. Guide wire diameters are specified in inches, typically
from 0.010 to 0.018 in. in increments of 0.002 in. Larger
thickness wires are required for peripheral vessels. Wire diameter and construction determine torquability and compatibility with various balloon catheter systems. Larger wire
diameter provides better torquability, but the larger wire diameter generally means the angioplasty balloon cannot be as
low profile, all else being equal. Thus, low profile balloon
catheters, desirable because of their superior ability to cross
tight lesions, generally must be used with smaller gauge
guide wires that are more difficult to maneuver into place.
Angioplasty catheters and exchange systems: it is often
necessary to change balloon catheters, or, for example, to
switch to an imaging intravascular ultrasound catheter or intravascular brachytherapy source catheter, while leaving the
guide wire across the lesion. When this is done the guide
wire must be held in place by the operator while simultaneously pulling back on the catheter. If the catheter is a
central lumen, over-the-wire type, the wire must be long
enough that the entire catheter can be removed from the
guide catheter while the operator continues to hold the proximal end of the wire, or else friction with the catheter will
pull the wire from its place across the lesion. Thus, guide
wires designed to allow over-the-wire catheters to be ex-
128
Nath et al.: Intravascular brachytherapy physics
128
FIG. 5. Radial dose functions for monoenergetic photons and electrons under the point source approximation.
changed, so-called ‘‘exchange wires,’’ are 300 cm long,
more than twice as long as the standard balloon catheter
length of 135 cm. Many standard ~nonexchange! guide
wires, although only 175 cm long, allow an extension wire to
be attached to the proximal end via a threaded or spring
mechanism so that catheter exchanges may be performed.
Other systems for exchanging intracoronary catheters have
been developed, the most widespread of which is the
‘‘monorail’’ system that uses catheters in which only a short
segment at the distal end slides along the wire, so that the
wire and the catheter exit the guide catheter separately except for the last few centimeters at the distal end.
Catheter-based brachytherapy systems must meet the
same general constraints as other angioplasty devices, i.e.,
they must be ~1! small enough to pass through a standard 7
or 8 French guiding catheter; ~2! flexible and pushable
enough to track through tortuous anatomy with radii of curvature of 5 mm or less and diameter of 2–3 mm, without
damaging the arterial wall; ~3! small enough to be safely
Medical Physics, Vol. 26, No. 2, February 1999
advanced through the target lesion; ~4! compatible with standard guide wires and catheters, preferably with a monorail
design for ease of exchange with the balloon or stent delivery catheter; ~5! visible under fluoroscopy for precise localization of the dose relative to the treatment area; and ~6!
reliably constructed so that there is negligible risk of a device failure resulting in injury to the patient.
V. DOSIMETRY STUDIES OF INTRAVASCULAR
BRACHYTHERAPY
To address some of the dosimetry related issues in intravascular brachytherapy, a brief summary of selected papers
is presented in this section. Because of the sparse number of
studies available in the literature, the task group was unable
to present critical evaluation, reference dosimetry data, or
recommendation of a quantitative nature. However, the de-
129
Nath et al.: Intravascular brachytherapy physics
129
TABLE I. Some of the possible radionuclides for intravascular brachytherapy.a
Radionuclide
32
P
Y
90 c
Sr
192
Ir
103
Pd
125
I
48
V
106
Rh
188
Re
90
Emission
Maximumb
energy ~keV!
Average energy
~keV!
Half-life
Delivery
systeme
beta
beta
beta
gamma
x ray
x ray
positron
beta
beta
1710
2282
546
612
23
35
696
923
2120
695
934
196
370d
21d
28d
144
307
765
14.28 days
2.671 days
28.5 yr
73.831 days
16.97 days
60.14 days
15.976 days
2.17 h
16.98 h
C,S,L
C,S,L
C
C
S
S
S
L
L
All other data from the Table of Radioactive Isotopes ~Ref. 51!.
The maximum energy of photons with a yield greater than 1%.
c
Practical sources of 90Sr always have 90Y in equilibrium.
d
Average photon energy from AAPM Task Group No. 43 ~Ref. 52!.
e
C, S, and L in the delivery system column denote the catheter-based system, radioactive stent, and radioactive
liquid in a balloon, respectively.
a
b
scription of selected papers presented below is designed to
alert the medical physics community regarding some of the
pertinent dosimetry issues.
A. Dosimetry studies of gamma emitting seeds and
wires
Dose distributions for point or line source gamma and
x-ray emitters used in interstitial brachytherapy of cancer
have been well studied both theoretically and experimentally, mostly at distances of 1 cm or more. At distances
smaller than 5 mm, which are of interest in intravascular
brachytherapy, measurements are difficult due to the extremely large dose gradients and other technical considerations. At small distances from the source, dose perturbations caused by scatter and self-absorption of low-energy
secondary radiations also make theoretical calculations difficult.
Amols et al.53 recently presented analytical calculations
of dose distributions and dose rates for 192Ir, 125I, 103Pd, 32P,
and 90Sr for use in intracoronary irradiation. The effects of
source geometry and positioning accuracy were studied. Although some of the dosimetry parameters are not accurately
known at distances of less than 1 cm, linear extrapolation of
data given by the AAPM Task Group ~TG! No. 4352 yielded
reasonably accurate results, as demonstrated in Fig. 6, which
compares calculated and measured values of dose versus radial distance from a single 192Ir source 0.5 mm diam and 3
mm length. In this study, dose was measured by sandwiching
an 192Ir seed between multiple slices of GafChromic™ film
in a water equivalent plastic phantom for several hours. Using these dosimetry data isodose distribution in the axial
plane around a linear array of five 192Ir seeds with 2 mm
spacing between seeds was calculated ~Fig. 7!. This dose
distribution is typical of that used for the irradiation of coronary arteries in various preclinical studies. It is also typical
of the doses that would be obtained with an HDR unit programmed to treat a 2–3 cm length of artery. The dose distribution at the internal surface of the arterial wall ~approximate radial distance51.5 mm) is seen to be relatively
Medical Physics, Vol. 26, No. 2, February 1999
uniform ~610%! with a rapid dose falloff radially and axially beyond the extent of the implant volume ~noted schematically in Fig. 7 by the dashed seed locations!. The highest
dose at a radial distance of 1.5 mm was normalized to 100%,
and only half of the implant zone is plotted ~the graph would
be symmetric about the axial center of the implant!. The total
length of the implant volume is approximately 22 mm.
Recently Li et al.54 used the Monte Carlo photon transport ~MCPT, a code developed by Williamson at the University of Washington! simulation in the dosimetric characterization of various brachytherapy sources for intravascular
brachytherapy. This study used MCPT calculations to evaluate
the dose distribution of stainless steel encapsulated 192Ir
seeds at the range of 1 to 20 mm from center of the source.
The results were reported using the AAPM TG-43 formalism. In particular, the radial dose function and the anisotropy
function are tabulated and compared with data given in the
AAPM TG-43 report. Agreement to within 3% was found
between the MCPT calculation results and the AAPM TG-43
reference data for most of the data points. It was found that
MCPT-derived values of radial dose function agree to within
1% with the polynomial fitted radial dose function of the
192
Ir seeds given in the AAPM TG-43 report at distances of 1
mm to 1 cm and 2% at distances between 1 and 4.5 cm. The
largest discrepancies were observed in anisotropy functions
along the source longitudinal axis.
B. Dosimetry studies of beta emitting seeds and
wires
In 1995, Popowski et al.55 developed a beta emitter for
intravascular brachytherapy and performed extensive dosimetry measurements using thermoluminescent dosimeters
~TLDs!. Nonradioactive flexible 89Y wires ~diameter of 0.15
and 0.26 mm! were activated within the thermal neutron flux
of an experimental reactor. Standard angioplasty balloons ~2
cm long, 2.5 mm in diameter when inflated! were inserted
for dosimetry into a specially manufactured tissue equivalent
phantom. Four wells, drilled perpendicular to the axis of the
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Nath et al.: Intravascular brachytherapy physics
130
TABLE II. Stent types.
Company
Stent name
Material
J&J
Cook
AVE
Pfizer
Guidant
Medtronic
Cordis
Boston
InStent
PAS
Palmaz–Schatz
Gianturco–Roubin
MicroStent
Wallstent
Multilink
Wiktor
¯
¯
CardioCoil
ACT-1
Stainless steel
Stainless steel
Stainless steel
Stainless steel
Stainless steel
Tantalum
Tantalum
Nitinol™
Nitinol
Nitinol
balloon, allowed for the insertion of thin, flexible TLDs
~disks of 2 mm diam! and spacers. The angioplasty balloon
was inflated with air or with contrast media. Radioactive 90Y
wires were left in the central lumen of the balloon for two
minutes. Doses at the surface of the balloon and at 1, 2, and
3 mm were determined from TLD readings. Doses obtained
at the surface of the balloon for a two-minute exposure for
the 0.26 mm wire ~balloon inflated with air! and the 0.15 mm
wire ~air or contrast! were 56.5, 17.8, and 5.4 Gy, respectively. As expected for a beta emitter, the falloff in dose as a
function of depth was rapid. External irradiation from the
beta source was negligible. Popowski’s experiments indicate
that the dose rates attainable at the surface of the angioplasty
balloon using this technique allow the doses necessary for
the inhibition of intimal cell proliferation to be reached
within a relatively short period of time. They conclude that
the thin 90Y wires are very easy to handle and their mechanical and radioactive properties are well suited to the requirements of the catheterization procedure.
Soares56 presented the dose evaluation of a 90Sr source
developed for intravascular brachytherapy at Emory University. The dosimetry and characterization of this catheterbased beta-particle emitting brachytherapy source was accomplished in three distinct steps. The first step involved a
characterization of seed sources to determine the axial and
transaxial uniformity of each seed, as determined by measurements near contact and at 3 mm in a tissue-equivalent
material such as A150 plastic. Since there were no axial
orientation markings on these very small sources, uniformity
of the dose rate perpendicular to the seed axis was crucial to
obtaining reproducible results. Once a seed demonstrated
suitable axial and transaxial uniformity, it was used in the
second step, which involved the measurement of the
absorbed-dose rate at a depth of 2 mm in a water equivalent
medium. Next, this seed was used in the third step, which
involved radiochromic film measurements at several depths
in a water-equivalent phantom; the information resulting
from these irradiations were then used to construct tables of
data that were used to determine the dose rate at any arbitrary point in the tissue-equivalent phantom. Finally, guidance was given for determining the dose rate in media other
than the tissue-equivalent material. Each of these topics are
discussed in more detail in a later section of this report.
Recently, Xu et al.57 presented dose measurements for a
Medical Physics, Vol. 26, No. 2, February 1999
Radiopacity
Low
Low
Medium
Low
Low
High
Very high
¯
High
High
Shape
Deployment
Slotted tube
Coil
s curves
Mesh
Slotted tube
Coil
s curves
¯
Coil
Slotted tube
Balloon
Balloon
Balloon
Self-expanding
Balloon
Balloon
Balloon
Self-expanding
Self-expanding
Balloon
32
P source developed for intravascular brachytherapy. They
used TLDs for distances up to 1–5 mm and scintillation
detectors. A calibration jig was developed for determining
the total source activity and its nonuniform activity distribution along a 32P source designed for endovascular irradiation.
The 32P source was 27 mm in length and 0.3 mm in diameter
and was embedded in the end of a NiTi wire. The distribution of the source activity was obtained and a total activity of
12.25 mCi was determined, which was in agreement with the
value measured using a well-type chamber. The radial dose
rate distributions were measured using GafChromic film and
calculated assuming a both nonuniform and uniform source.
The results showed that the best agreement was achieved
between the measured and calculated data if the nonuniform
source activity was taken into account. These results have
been further verified by Monte Carlo dosimetry.58
C. Dose inhomogeneity due to noncentering of source
Amols et al.53 calculated dose asymmetry resulting from
inaccurate source centering of a catheter-based system. In
Fig. 8 the magnitude of the dose asymmetry resulting from
centering errors of 30 mm long 90Sr/Y and 192Ir wires is
shown. Plotted are the ratios of the maximum dose to the
vessel wall divided by the minimum dose in a cylindrical
vessel 5 mm in diameter as a function of centering offset. As
seen, centering errors as small as 0.5 mm in a 5 mm diam
vessel result in dose asymmetries of 1.6 for 192Ir, and 2.1 for
90
Sr/Y. For catheter-based delivery systems, dose uniformity
to the arterial wall depends critically on centering the source
within the artery and the cylindrical symmetry of the artery
itself. Amols et al. concluded that centering is more critical
for beta emitters than gammas.
Dose uniformity can be improved if the design of the
balloon catheter incorporates some method of centering the
source. Popowski et al.59,60 presented a dosimetric evaluation
of such a new device dedicated to intravascular irradiation,
associating a beta source and a centering device prior to initiation of a clinical pilot study. A 29 mm long 90Y coil,
coated with titanium and fixed to the end of a thrust wire,
was introduced into the inner lumen of centering balloons of
different diameters ~2.5, 3, 3.5, and 4 mm!. Dose homogeneity was evaluated by studying both axial and circumferential
dose variations, based on readings from TLDs placed on the
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Nath et al.: Intravascular brachytherapy physics
balloon surface. Axial homogeneity was determined by comparing the readout values of dosimeters located on peripheral
balloon segments compared to those located on segments
adjacent to the midpoint of the source. The centering ability
of the device was studied by comparing measurements on
opposing surfaces of the balloon. The dose attenuation by
water and contrast medium was evaluated and compared
with that in air. The total 90Y coil activity was measured by
liquid scintillation in order to relate activity to surface dose.
The activity–surface dose correlation showed that for a linear coil activity of 1 mCi/mm the mean dose rate at the
surface of a 2.5 mm balloon filled with contrast medium was
8.29 Gy/min. The doses at the surface of larger balloons ~3,
3.5, and 4 mm! filled with contrast were 78%, 59%, and
47%, respectively, of the dose measured at the surface of the
2.5 mm balloon ~Fig. 9!. The coefficient of variation ~CV! in
the surface dose for 2.5, 3, 3.5, and 4 mm centering devices
filled with contrast medium were 9%, 8%, 9%, and 12%,
respectively. There was no statistically significant difference
between readouts from central and peripheral balloon segments or among rows of dosimeters facing each other. For a
2.5 mm balloon compared with air, the dose attenuation by
water and contrast medium was similar ~0.70 and 0.69, respectively!, but a significant difference was seen between the
readouts of water- and contrast-filled balloons when the diameter was larger than 3 mm (p,0.001). No contamination
was found in the balloon shaft after source retrieval. The
dosimetric tests showed very good surface dose homogeneity, demonstrating satisfactory centering of the source within
the centering balloons. From this study Popowski et al. concluded that the achievable dose rates will permit intravascular irradiation with a beta emitter within a short time interval.
131
FIG. 6. Calculated and measured ~using GafChromic film! radial dose versus
distance for 0.5 mm diam, 3.0 mm length 192Ir sources. Doses are plotted on
an absolute scale of cGY h21 mCi21, with no artificial normalization.
~Adapted from Int. J. Radiat. Oncol., Biol., Phys., H. I. Amols, M. Zaider, J.
Weinberger, R. Ennis, P. B. Schiff, and L. E. Reinstein, ‘‘Dosimetric considerations for catheter-based beta and gamma emitters in the therapy of
neointimal hyperplasia in human coronary arteries,’’ 1996, Vol. 36, with
permission from Elsevier Science.!
gamma emitters 103Pd, 125I, and 192Ir; and beta emitters 90Sr,
32
P, and 90Y using the ITS Monte Carlo code for the simulation of electron–photon transport. They used unencapsulated
point sources of these radionuclides in these calculations,
which included the entire spectra of beta and gamma emissions from each radionuclide and charged particle transport
of secondary radiations ~Fig. 11!. They concluded that for
depths up to 10 mm, even low-energy gamma emitters of
103
Pd and 125I provide as good dose penetration in depth as
192
Ir. However, the specific activity of 125I or 103Pd is too low
for a catheter-based system.
D. Comparison of depth dose from gamma and beta
rays
E. Dosimetry studies of permanent radioactive stents
Calculations of dose from internally deposited beta-minus
emitters is also a well-studied problem, with rigorous reports
presented by Loevinger.61 Recently, a version of this method
was used by Amols et al.51 to estimate dose distributions
produced by point sources of beta emitters. Radial dose distributions for either 32P or 90Sr/Y beta sources were compared with similar data for 192Ir ~Fig. 10!. All doses were
normalized to unity at a radial distance of 2 mm. The short
range of the beta particles results in a more rapid dose falloff
versus distance than the 192Ir gamma source. 32P with the
lowest transition energy has the shortest radial dose penetration. From this study, Amols et al. concluded that beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma
emitters deliver larger doses to normal tissues and to staff.
Low-energy x-ray emitters such as 125I and 103Pd reduce
these risks but are not available at high enough activities.
They found that accurate source centering is of great importance. If this can be accomplished, then high-energy beta
emitters such as 90Y or 90S/90Y would be ideal sources. Otherwise gamma emitters such as 192Ir may be optimal.
Nath et al.50 determined the radial dose function for
Fischell et al.62 have used stents into which 32P was permanently implanted just below the stent outer surface. Typical dimensions of the stent are 20 mm in length with diameters of 3, 4, and 5 mm. Most of the work in coronary
arteries involves the 3 mm diam stent. Activities as low as 5
kBq ~0.13 mCi! have been considered. In 1995, Prestwich
et al.63 presented the results of a calculation of the dose distribution surrounding uniform cylinders of 32P in order to
obtain information relevant to the utilization of radioactive
stents. The dose distribution surrounding a cylindrical source
of 32P was estimated by the dose-point-kernel method employing numerical integration. Cylinders 20 mm in length
with diameters of 3, 4, and 5 mm were considered. The radial distribution is cusp shaped for planes within the length
of the cylinder, becoming monotonic for planes beyond the
ends of the cylinder. The dose variation from the cylinder
wall was roughly exponential and the dose at a specific distance from the wall decreases with cylinder diameter.
In a later study, Prestwich et al.64 represented the dose
along the radial direction located at the midplane of a radioactive stent, simulated by a uniform cylinder of 32P by an
analytical function consisting of the sum of two modified
Medical Physics, Vol. 26, No. 2, February 1999
132
Nath et al.: Intravascular brachytherapy physics
FIG. 7. Calculated isodose distribution in the axial plane for a linear array of
5 192Ir seeds ~2 mm spacing between seeds, as indicated by thick solid lines!.
The highest dose at a radial distance of 1.5 mm ~dashed line! was normalized to 100% and only half of the implant zone is plotted ~the implant is
symmetric about the axial center!. The total length of the implant volume is
approximately 22 mm. ~adapted, with permission, from the American College of Cardiology, Journal of the American College of Cardiology, 1994,
Vol. 23, No. 6, pp. 1491–1498.!
exponentials. This procedure reproduces values obtained
from numerical integration, for which no closed form exists,
to within 5% for distances up to 6 mm from the wall and for
stent diameters from 2–6 mm.
Coffey and Duggan65 calculated the dose to tissue from a
1 mCi 32P stent using the dose-point-kernel method, assuming the tissue outside the stent is homogeneous and uniform
with properties close to that of water. The cylindrical geometry for a Palmaz–Schatz coronary stent was introduced into
the model calculation since this device is the most widely
used coronary stent. Dose maps were calculated for distances
ranging from 0.1 to 3 mm radially out from the stent surface.
The results were compared to actual measurements made using radiochromic film dosimetry from a 32P impregnated
Palmaz–Schatz stent produced by an ion implantation process. In this study, verification of the Prestwich model for 32P
stents ~modified Strecker and Palmaz–Schatz! was provided
by measuring a dose for the radial distance from 0.5 to 5 mm
from the stent surface using radiochromic film dosimetry
~Fig. 12!.
Duggan et al.66 described a model similar to the point
dose kernel models of Berger, Brookeman, and Prestwich for
the estimation of the dose distribution surrounding a pure
beta-emitting 32P coronary stent. In addition, radiochromic
dosimetry methods were utilized to experimentally determine the absolute dose and relative dose distributions parallel to the short axis of a 32P Strecker stent ~0.22 cm diam and
2.0 cm length, 2.15 mCi! and parallel to the short axis of half
a 32P Palmaz–Schatz stent ~0.35 cm diam and 0.70 cm
length, 8.4 mCi!. Correlation of theoretical dose calculation
methods and experimental dose distribution results were reported as encouraging. This study provides verification of a
theoretical model by measuring a dose with radiochromic
film for radial distances from 0.25 to 3 mm from the stent
surface and axial distances of up to 4 mm from the center of
Medical Physics, Vol. 26, No. 2, February 1999
132
the stent ~Fig. 13!. The peaks at 0.2 mm distance represent
the extremely high dose areas in the immediate vicinity of
the wire mesh of the stent.
Janicki et al.67 calculated the near-field dose distribution
of a realistic 32P impregnated vascular stent employing the
dose-point-kernel method in a homogeneous medium. The
cylindrical wire mesh geometry for the Palmaz–Schatz stent
was numerically introduced in the model calculation, and the
dose distribution of the 32P beta emitting isotope was computed at distances ranging from 0.1 to 3 mm from the outside
of the stent surface. Measurements made using radiochromic
film dosimetry of the dose from Palmaz–Schatz stents impregnated with 32P produced by shallow ion implantation
were used to validate the model at radial distances from 0.11
to 4 mm from the stent surface and axial distances of up to 4
mm from the center of the stent ~Fig. 14!. The close agreement between the model and the film dosimetry results confirmed the validity of this geometry-specific model. As reported recently by Janicki et al.,68 this calculational dosepoint-kernel methodology can be adapted to any stent design
to yield dose distribution results. Finally, Whiting et al.69
reported computed dose distributions surrounding a Palmaz–
Schatz stent using the Monte Carlo N-particle ~MCNP! transport code, which agreed well with the results from Janicki’s
model.
In 1995, Ly et al. ~aka Li!70,71 reported a feasibility study
and preliminary dosimetry for a brachytherapy source based
on proton-beam activation of a removable intracoronary stent
made of shape–memory nickel–titanium alloy ~Nitinol™!.
The stent was activated by 8.5 MeV proton bombardment to
produce Vanadium-48: 48Ti(p,n) 48V. Due to the high attenuation of the protons by Nitinol, the stent was rotated
axially during proton bombardment to achieve uniform activation. A 16.0 day half-life and gamma emissions of 0.511,
0.945, 0.983, 1.312, and 2.241 MeV were measured by spectral analysis to confirm the production of 48V. All other activation products were decayed to the background by three
days. Despite the presence of penetrating gamma emissions,
over 96% of the dose within 1.0 mm of a 48V stent was from
positron absorption, and the dose at 10 cm from the stent was
less than 0.02% of the treatment dose. GAF Chromic™ film
~23 mm thick active polymer emulsion! was calibrated with a
60
Co radiation treatment beam and was used to measure dose
distributions for five planes parallel to the stent long axis,
spaced 126 mm apart. The complete three-dimensional dose
distribution surrounding the stent was estimated by computing the dose distribution for a single ‘‘strut’’ segment by
Monte Carlo calculation ~MCNP version 4a!, then using this
as a ‘‘strut dose kernel’’ to perform a summation over all 48
struts making up the stent. The absolute dose based on this
calculation and measured total 48V activity agreed with the
direct radiochromic film measurements to better than 10%.
Full three-dimensional dose distributions can be computed
for stents expanded to any diameter, and even for irregularly
deployed stems, allowing detailed dose descriptions throughout the treatment volume ~an example is shown in Fig. 15!.
133
Nath et al.: Intravascular brachytherapy physics
133
biological half-life of about 10 h! are bone seeking compounds, the whole body and bone marrow doses that would
ensue after a balloon rupture are unacceptably high ~100–
1000 cGy!. New data on 90Y and 188Re chelates, which have
short biological half-lives, indicate that those risks may be
reduced to a tolerable level.
VI. RECOMMENDATIONS FOR INTRAVASCULAR
BRACHYTHERAPY PHYSICS
A. Dose specification and renormalization for
catheter-based intravascular brachytherapy systems
FIG. 8. Dose asymmetry resulting from centering errors of 30 mm long wire
source of 90Sr/90Y, or 192Ir. Plotted are the ratios of the maximum dose to
the vessel wall divided by the minimum dose in a cylindrical vessel 5 mm in
diameter as a function of the centering offset. When the source is centered
the dose asymmetry is 1.0. ~Adapted from Int. J. Radiat. Oncol., Biol.,
Phys., H. I. Amols, M. Zaider, J. Weinberger, R. Ennis, P. B. Schiff, and L.
E. Reinstein, ‘‘Dosimetric considerations for catheter-based beta and
gamma emitters in the therapy of neointimal hyperplasia in human coronary
arteries,’’ 1996, Vol. 36, with permission from Elsevier Science.!
F. Dosimetry studies of radioactive liquid filled
balloon catheter
One possible irradiation technique, presented by Amols
et al.72 is to inflate the balloon dilatation catheter with a radioactive solution. It has advantages over other proposed irradiation procedures, in that accurate source positioning and
a uniform dose to the vessel wall are assured as long as the
artery is not already stented. Experimental measurements
and analytical calculations of the dose distribution around a 3
mm diam by 20 mm long balloon filled with a 90Y-chloride
solution were also presented. The dose rate at the surface of
the balloon was approximately 0.14 cGy/s per mCi/ml
(3.78310211 Gy/s per Bq/ml, with the dose decreasing to
53% at 0.5 mm, and ,5% at a 3.5 mm radial distance. Whiting et al.69 have shown that unlike solid intracatheter sources
and stents, the dose rate at a given depth in tissue from a
liquid isotope balloon source increases with an increased
vessel size. Amols et al.72 concluded that 90Y and other possible isotopes are currently available at specific concentrations >50 mCi/ml (1.853109 Bq/ml), which enables the delivery of 20 Gy in less than five minutes. In Fig. 16, the
calculated and measured dose rate versus the radial distance
from the center of a 3 mm diam by 20 mm long balloon
(total volume50.14 ml) filled with a 90Y solution are shown.
The dose is plotted in units of cGy s21 mCi21 ml21. The
measured data were obtained using GafChromic film, as described above. Agreement between measurements and calculations is 63%. While this technique clearly yields desirable
dose distributions, the chemical and radiological toxicity of
the radioactive liquid must be considered, as there is a risk of
balloon rupture with present catheter design ~approximately
0.1%!. Since most commonly available beta emitters ~and all
of those listed in Table I, except for 188Re, which in the form
of 188Re perchenate as eluted from a 188W/188Re generator is
not a bone seeker and is eliminated via the urine with a
Medical Physics, Vol. 26, No. 2, February 1999
The irradiation techniques and specification of radiation
doses in various studies using catheter-based intravascular
brachytherapy differ from each other significantly, making a
direct comparison of the techniques difficult. This AAPM
task group reviewed the dosimetry of these catheter-based
intravascular brachytherapy techniques. An initial review indicated that different investigators have employed different
methods of dose specification. Some were using the dose to
the adventitia, some to the wall of the lumen, and some at
varying radial distances from the source center. This created
a great deal of confusion regarding the efficacy reported in
different studies at different dose levels. Therefore, the task
group decided to undertake a major scientific effort to renormalize the dosimetry to a common framework. This original
analysis was divided into three groups: ~1! catheter-based
systems using gamma emitters for peripheral vessels;40,43 ~2!
catheter-based systems using gamma emitters for coronary
vessels;45,32,33,30,44 and ~3! catheter-based systems using beta
emitters for coronary vessels.59,60,37
In order to use a common frame for comparing the dosimetry, it was assumed that in the peripheral vessel studies the
inner diameter of the vessel is 6 mm and in the coronary
arteries it is 3 mm. Assuming these common dimensions, the
doses to the luminal wall and at depths of 1, 2, and 3 mm
from the walls were calculated.
1. Catheter-based intravascular brachytherapy for
peripheral vessels using gamma emitter
Liermann et al.40 reported the use of a remote afterloading unit ~Nucletron MicroSelectron HDR! delivering an 192Ir
source of 10 Ci activity to the restenosis site in human femoropopliteal arteries. The delivery technique used a 5 French
close-ended catheter inserted into a non-self-centering 9
French catheter ~diameter 3 mm!. The prescription is specified as delivering 12 Gy to a distance of 3 mm from the
center of the source. The vessel segment has a diameter of 6
mm by use of an expanded 6 mm stent. It is therefore assumed that the vessel lumen surface is given 12 Gy. Depth
dose calculations were performed to obtain doses of 8.77,
5.51, 3.96, and 3.03 Gy at 4, 6, 8, and 10 mm from center of
the source, respectively. Actual minimum and maximum
doses delivered to the vessel wall were reported to be 8 and
28 Gy, due to the deviation of the catheter from the center of
the vessel.73
Waksman et al.43 used another remote afterloading ~Omnitron! unit for treatment of narrowed arteriovenous grafts,
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Nath et al.: Intravascular brachytherapy physics
134
FIG. 9. ~a! The mean dose rate expressed as a function of the balloon
diameter. The coil activity has been
normalized to a linear activity of 1
mCi/mm, which corresponds to a coil
activity of 29 mCi. ~b! A comparison
between dosimetric values read on peripheral ~P! and central ~C! balloon
segments. ~c! A comparison between
rows of four dosimeters ~D! and four
opposite ~O! dosimeters facing each
other on opposing surfaces of the balloon. ~d! Mean relative surface doses
normalized to that measured for an airfilled 2.5 mm balloon. The dose reduction is related to the filling medium
and balloon diameter ~reprinted from
Int. J. Radiat. Oncol., Biol., Phys., Y.
Popowski, V. Verin, M. Schwager
et al., ‘‘A novel system for intracoronary beta-irradiation: description and
dosimetric results,’’ 1996, Vol. 36,
with permission from Elsevier Science.!
giving a higher dose of 14 Gy at a depth of 0.5 mm from the
arterial wall. They have since then decommissioned the remote afterloading unit and switched to the same unit that
Liermann et al.40 used. A non-self-centering catheter is used.
FIG. 10. Radial dose versus distance for 192Ir, 32P, and 90Sr/90Y sources 0.65
mm diam and 5.0 mm length. Doses are normalized to 1.0 at a radial treatment distance of 2.0 mm. @Adapted from Int. J. Radiat. Oncol. Biol. Phys.,
H. I. Amols, M. Zaider, J. Weinberger, R. Ennis, P. B. Schiff, and L. E.
Reinstein, ‘‘Dosimetric considerations for catheter-based beta and gamma
emitters in the therapy of neointimal hyperplasia in human coronary arteries,’’ 1996, Vol. 36, with permission from Elsevier Science.!
Medical Physics, Vol. 26, No. 2, February 1999
Since the same remote afterloading unit and treatment planning system is used, it is relatively easy to compare the dose
specifications used in these studies. The ~Nucletron MicroSelectron NPS/PLATO! treatment planning system used for
this remote afterloading unit has optimization algorithms
that, in this treatment geometry, in effect increase the source
dwell times for dwell positions at the ends of the treated
length, so as to maintain dose homogeneity along the treated
vessel. The dose calculation algorithm models the source
~3.5 mm active length, 5 mm physical length! as a point
source, but is able to perform calculations based on dose
distribution anisotropy data at one given distance from the
source center. Tissue attenuation and scattering are corrected
for using the formula given by Van Kleffens and Star.74 For
the renormalization of dose specifications presented here, optimized dwell times are calculated using the same treatment
planning system, with optimization on dose points placed at
prescription distances from the source center for a treated
length of 4.5 cm with nine dwell positions, with a dwell
position step size of 5 mm. These dwell times are used to
calculate the renormalized dose distribution, corrected for
dose distribution anisotropy using the data from Williamson
135
Nath et al.: Intravascular brachytherapy physics
135
FIG. 11. Radial dose functions ~a! for gamma emitters
192
Ir, 125I, and 103Pd, and ~b! for beta emitters
90
Sr190Y, 188Re, 90Y, and 32P, using a point source
approximation.
and Li.75 The diameter of the treated vessel is assumed to be
6 mm.
Results of the renormalization process are given in Table
III. Average as well as the minimum and maximum doses
along the inner 4 cm of the treated length, calculated with a
1 mm grid size, are also given. It can be seen that the failure
to account for the dose distribution anisotropy, especially the
oblique filtration by source encapsulation, results in a 6%–
10% deviation in the actual delivered dose from the nominal
prescription dose. In addition, the dose distribution inhomogeneity is underestimated by the computer treatment planning system calculations, though to a smaller extent.
2. Catheter-based intravascular brachytherapy for
coronary vessels using gamma emitters
192
Ir seeds of the same design as those used in conventional low dose rate brachytherapy, but with higher activity
per seed, are also used for the treatment of coronary vessel
restenosis. Teirstein et al.45 uses ribbons of stainless steel
encapsulated 192Ir seeds, at activities up to 150 mCi per ribbon, to deliver a nominal prescription dose of 8 Gy to the
Medical Physics, Vol. 26, No. 2, February 1999
plaque and media region of human coronary vessels. The
interseed center spacing between 192Ir seeds is 4 mm, and
two lengths of ribbons, one using five seeds to obtain 1.9 cm
active length and the other using nine seeds to obtain 3.5 cm
active length, are used. The ribbon is manually inserted into
a non-self-centering 4 French catheter. Ultrasound scans are
obtained during the implant procedure to ensure that the
minimum and maximum doses to the media remain within
the range of 7 to 30 Gy. Dosimetric data for the ribbons at
the treated distance ~average 3.2 mm from the center of the
sources! is based on those by Kline et al.76
Weinberger’s group30 used ribbons of stainless steel encapsulated 192Ir seeds to deliver 20 Gy at a 1.5 mm distance
from the center of sources in an animal model. A non-selfcentering 4 French catheter within an 8 French guide catheter
is used. The ribbons contained five 192Ir seeds with 5 mm
interseed center spacing. Waksman et al.32,33 used ribbons of
stainless steel encapsulated 192Ir seeds in an animal coronary
vessel study. The 3 mm long seeds were contained in the
plastic ribbon, with no spacing between the seeds ~3 mm
interseed center spacing!. The study prescribes a dose of 3.5,
136
Nath et al.: Intravascular brachytherapy physics
136
FIG. 12. A plot of the radial dependence of the dose from a Palmaz–Schatz stent midway between the ends of the stent. The plot compares the values
calculated with a finite cylindrical shell model to those measured with radiochromic film in a phantom. ~Adapted from Int. J. Radiat. Oncol., Biol., Phys., D.
M. Duggan, C. W. Coffey, II, and S. Levit, ‘‘Dose distribution for a 32P-impregnated coronary stent: comparison of theoretical calculations and measurements
with radiochromic film,’’ 1996, Vol. 40, with permission from Elsevier Science.!
7, or 14 at a distance of 2 mm from center of the source,
along the transverse axis of the 192Ir ribbon. A non-selfcentering 4 French catheter within an 8 French guide catheter
is used.
Condado et al.44 reported the clinical experience of using
an 192Ir wire of 1.5 Ci activity delivered manually into coronary vessels. The dose is specified as delivering 20 or 25 Gy
at a distance of 1.5 mm from the center of the source. A
non-self-centering 4 French catheter is used in the study.
It should be noted that while both the Teirstein group and
the Condado group used non-self-centering 4 French catheters only for the delivery of treatment, the former group
adjusted treatment time using ultrasound measured media
thickness, to ensure that no part of the vessel wall received
more than 30 Gy dose, while the latter group exercised no
adjustment of the treatment time based on individual patient
measurement. The resulting hot spot in the latter case therefore can be more than 50 Gy, based on a prescription of 25
Gy to 1.5 mm distance from the center of 192Ir wire, using
the Sievert integral approximation.
Renormalization of prescribed doses as well as the dose
distribution at other points within the treated volume is performed in the same manner as the case for peripheral vessel
intravascular brachytherapy. For 192Ir ribbon-based techniques, the source activities and treatment times are first determined from the nominal prescription doses, using the
Kline et al.76 data for the Teirstein et al.45 technique and the
Condado et al.44 technique, and the point source approximation for the Waksman et al.32,33 technique and the
Weinberger30 technique. These activities and treatment times
Medical Physics, Vol. 26, No. 2, February 1999
are then used to recalculate dose distributions, using radial
dose function and anisotropy function data calculated by
Monte Carlo photon transport simulations54 for distances
smaller than 1 cm, in combination with the AAPM TG-43
report52 data for distances larger than 1 cm, while the dose
rate constant data are from the same AAPM task group report. The average, minimum, and maximum doses are calculated using the 1 mm calculation grid size along the treated
length, delimited by the centers of the 192Ir seeds at ends of
the ribbons. Coronary vessels are assumed to have a diameter
of 3 mm. The treated lengths are as specified by the respective studies. Results of the renormalization are given in
Table IV below. It can be seen that, due to the close distance
at which prescribed doses are specified, there can be significant uncertainty in the dose actually delivered.
3. Catheter-based intravascular brachytherapy
using beta emitter
Two groups have reported use of a beta-emitting source in
catheter-based intravascular brachytherapy. The Popowski
group59,60 in Berne, Switzerland, developed a balloon-fitted
catheter that is capable of self-centering within a coronary
vessel when the balloon is inflated. A 90Y wire was then used
in this catheter for treatment. Dosimetry data were obtained
using a TLD measurement technique. Waksman et al.37 experimented with a 2.5 cm long source train of five 90Sr/90Y
seeds, each of 5 mm length, with no spacing between the
seeds. Dosimetry data were calculated using the Monte Carlo
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137
FIG. 13. Plots of the dependence of the dose on the distance along the stent axis for fixed values of the radial distance from the surface of the stent. The plots
compare the values calculated with a finite length cylindrical shell model to those measured with radiochromic film in a phantom. ~a! Dose versus distance
along the stent axis for fixed radial distances from a stent surface of 0.112 and 0.328 mm. ~b! Dose versus distance along the stent axis for fixed radial
distances from a stent surface of 0.436, 0.549, 0.784, and 1.039 mm. ~c! Dose versus distance along the stent axis for fixed radial distances from a stent surface
of 1.294, 1.549, 1.804, and 2.058 mm. ~Adapted from Int. J. Radiat. Oncol. Biol. Phys., D. M. Duggan, C. W. Coffey, II, and S. Levit, ‘‘Dose distribution for
a 32P-impregnated coronary stent: comparison of theoretical calculations and measurements with radiochromic film,’’ Vol. 40, 1996, with permission from
Elsevier Science.!
simulation technique.77 Dose distribution data from these reports are used directly to obtain the values given in Table V.
4. Recommendations on dose prescription for a
catheter-based system
Results of the above analysis indicate a wide variation in
dose specification for catheter-based intravascular brachytherapy, in the extreme case by as much as 56%. When these
results were first presented to the cardiology community it
became apparent to them that a careful analysis of dosimetry
by a qualified medical physicist has great merit in making a
meaningful evaluation of the results of preclinical and cliniMedical Physics, Vol. 26, No. 2, February 1999
cal studies using ionizing radiation. These data ~Tables
III–V! have, in fact, resolved a puzzling lack of efficacy in
some of the studies by showing that the reported doses were,
in fact, too low compared to those in other studies showing
efficacy because of the choice of a different point for dose
specification.
Based upon the above analysis of dose specification and
its renormalization in preclinical and clinical studies on
catheter-based studies, the task group recognizes that a uniform practice of dose reporting is needed. To this end, the
task group recommends that prescription for a catheter-based
system should be in terms of a dose delivered at a reference
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138
FIG. 14. Measured dose profiles ~dots! and the dose point kernel ~DPK! model predictions ~solid lines! taken at u 530° and along the long axis of the 3.5 mm
diam one-half Palmaz–Schatz stent impregnated with 32P, at radial distance d of ~a! 0.112 mm, ~b! 0.328 mm, ~c! 0.436 mm, ~d! 0.784 mm, ~e! 1.039 mm,
~f! 1.294 mm, ~g! 1.549 mm, and ~h! 1.804 mm exterior to the stent surface. All dose values are normalized to a 14.3 days exposure with an initial activity
A 0 537 kBq ~1 mCi!. The agreement between the experimental dose profiles and the dose-point-kernel model predictions is very satisfactory, despite some
large discrepancies over limited regions for some scans, which can be explained by scanning artifacts. ~Reprinted with permission from Janicki, Duggan,
Coffey, Fischell, and Fischell, ‘‘Radiation dose from a p-32 impregnated Palmaz–Schatz wire mesh vascular stent,’’ Med. Phys. 24, 437–445. Copyright
1997, American Association of Physicists in Medicine.!
distance in water. For intracoronary application, a reference
distance of 2 mm from the source center is recommended.
For a larger, peripheral vessel the reference distance should
be 2 mm larger than the average lumen radius of the vessels
under study.
For the coronary arteries, the choice of 2 mm as a reference distance provides a dose specification relative to the
source location, which can be easily reproduced and verified
by a data review committee in a multi-institutional study.
However, it suffers from the fact that it does not express dose
delivered to an anatomical structure, e.g., the lumen wall,
adventitia, etc. In fact, for any given patient the lesion is
likely to be eccentric and vary in thickness and eccentricity
along its length; therefore doses to any given anatomic structure such as the lumen wall are going to vary widely. The
recommendation regarding dose specification for peripheral
vessels is dose at a depth of 2 mm from the average lumen
radius because peripheral vessels can be much larger than
Medical Physics, Vol. 26, No. 2, February 1999
coronary vessels. In a larger vessel the centering of the
catheter-based source becomes more important because of
the larger potential for eccentricity and consequently hot and
cold spots.
Ideally a three-dimensional dose distribution over the entire irradiated volume should be generated for each specific
patient. If detailed three-dimensional quantitative measurements such as those from an IVUS study are available, the
average, minimum, and maximum doses delivered should be
estimated for each clinical case. These dosimetry parameters
should be determined in at least three planes perpendicular to
the catheter and along its length over the lesion.
Because of the potential of a significant market, a large
number of commercial vendors are developing various delivery systems for intravascular brachytherapy. In order to
evaluate different systems it is important to compare them
using a common specification. Even though it is too early to
develop a rigid standard for intravascular brachytherapy sys-
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Nath et al.: Intravascular brachytherapy physics
FIG. 15. A comparison of dose distributions for two radioactive stents, both
expanded to 3.0 mm diameter ~inner dashed circle!. Top: isodose contour
plots for a 15 mm long Palmaz–Schatz stent with a surface layer of 32P,
total activity 1.0 mCi. Bottom: isodose contour plots for a 15 mm long
ACT-One stent uniformly activated with 48V, total activity 5.0 mCi. Left
and right plots are for the most uniform ~‘‘12-strut’’ section! and least
uniform ~‘‘6-strut’’ or mid-slot section! cross sections, respectively, for both
stents. The activities were chosen to give approximately the same dose of 12
Gy to a depth of 0.5 mm ~outer dashed circle! for both stents. Note that the
dose for the 32P stent is significantly more homogeneous than that for 48V,
which has a maximum beta energy of only about half that of 32P.
tems, the task group strongly recommends that the following
minimum specifications should be used in evaluating all
catheter-based systems.
~1! The output of all commercial systems for coronary applications should be specified in terms of dose rate in
water at a radial distance of 2 mm from the center of the
source.
~2! The penetrating ability of all commercial systems should
be specified in terms of the radial dose function normalized at a radial distance of 2 mm. The radial dose function should cover at least a range of radial distances from
0.5 to 10 mm ~or R 90 , 90% of the electron range for beta
emitters! at 0.5 mm intervals.
~3! Uniformity of the dose delivered at points along the
source–axis should be better than 610% ~range of values from minimum to maximum in the centered twothirds of the treatment length of at least 3 cm! at a radial
distance of 2 mm from the source axis.
~4! Uniformity of a dose at the points in a circle of 2 mm
radius centered on the course axis should also be within
610% in the centered two-thirds of a minimum treatment length of 3 cm.
These task group recommendations are achievable by
most of the commercial systems. Therefore, it is considered
to be a reasonably attainable standard.
Medical Physics, Vol. 26, No. 2, February 1999
139
FIG. 16. Calculated ~solid curve! and measured ~solid curve with stars! dose
rates ~cGy s21 mCi21 ml21! versus the radial distance ~mm! from the center
of a 90Y filled balloon 3.0 mm diam and 20.0 mm length. Plotted for comparative purposes is the dose versus radial distance for a 90Y wire source
~normalized at a radial distance of 1.5 mm to the dose rate for the balloon!,
demonstrating that the radial falloff for a balloon is slightly greater than for
a wire ~dashed curve with open squares!. ~Adapted with permission from
Amols, Reinstein, and Weinberger, ‘‘Dosimetry of a radioactive coronary
balloon dilatation catheter for treatment of neointimal hyperplasia,’’ Med.
Phys. 23, 1783–1788. Copyright 1996, American Association of Physicists
in Medicine.!
B. Dosimetric characterization of catheter-based
intravascular brachytherapy systems
1. Dosimetry of catheter-based gamma emitters
The AAPM recommends the use of the TG-43 dose calculation formalism for catheter-based intravascular brachytherapy systems using photon-emitting sources. The TG-43
formalism recommends that the dose at a point (r, u ), as
shown in Fig. 17, be calculated using
D ~ r, u ! 5S K L @ G ~ r, u ! /G ~ r 0 , u 0 !# g ~ r ! F ~ r, u ! ,
~1!
where S K 5air kerma strength, L5dose rate constant, r
5radial distance from the source, u 5angle between the line
segment from point of interest to center of source, as measured from a line containing the source’s long axis, F(r, u )
5anisotropy factor describing the dose variation versus
angle. This function is normalized to unity at u 590°,
G(r, u )5geometry factor resulting from spatial distribution
of the radioactivity within the source, g(r)5radial dose
function, and (r 0 , u 0 )5the polar coordinates of the reference
point.
The reference point recommended by TG-43 is the point
on the transverse axis at a distance of 1 cm, i.e., r 0 51 cm
and u 0 5 p /2. Under the point source approximation, the geometry factor and radial dose function are
G ~ r, u ! .
1
,
r2
g ~ r,r 0 ! '
D~ r ! r2
.
D ~ r 0 ! r 20
~2!
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Nath et al.: Intravascular brachytherapy physics
140
TABLE III. Dose distribution of gamma emitter intravascular brachytherapy in peripheral vessels.
Author→
Type of study
Type of catheter
Nominal prescription
dose
Normalized prescription
dose
Average, minimum,
and maximum dose at
vessel surfaceb
Average, minimum,
and maximum dose at 1
mm depthb
Average, minimum,
and maximum dose at 2
mm depthb
Average, minimum,
and maximum dose at 3
mm depthb
Liermann et al. 1994 ~Ref. 40!
Clinical trial, peripheral vessel
stenosis
Non-self-centering, 5 French
catheter in a 9 French catheter
Waksman et al. 1996 ~Ref. 43!
12 Gy to 3 mm from the source
center
10.9 Gy
Clinical trial, occluded
arteriovenous graft
Non-self-centering, 5
French catheter in a 9
French catheter
14 Gy to 0.5 mm from
the vessel wall
12.9 Gy
10.7 Gy
10.4 Gy
11.1 Gya
7.7 Gy
7.1 Gy
7.9 Gy
5.9 Gy
5.2 Gy
6.1 Gy
4.8 Gy
4.1 Gy
5.0 Gy
15.4 Gy
14.8 Gy
16.5 Gy
11.1 Gy
10.7 Gy
11.3 Gy
8.6 Gy
7.8 Gy
8.7 Gya
6.9 Gy
6.0 Gy
7.1 Gy
a
Indicates the dose prescription point position.
Assuming a lumen diameter of 6 mm and exact source centering.
b
Using the TG-43 notation, the dose at a distance r from a
source under the point source approximation can be expressed as
D ~ r ! .S K L
r 20
r2
g ~ r ! f avg ,
~3!
where f avg is the average anisotropy factor.
For a line source, the geometry factor is
G ~ r, u ! 5
b
,
Lr sin u
~4!
where b is the angle subtended by the active length L at the
point of interest.
The strength of the gamma-emitter source should be determined in terms of its air kerma strength, as described in
the AAPM TG-43 report. The air kerma strength of the intravascular brachytherapy source should be traceable to a
NIST standard or to an ADCL standard. For gamma-emitting
sources these procedures for the specification and determination of source strength are identical to those described in the
TG-43 report.
Because distances of interest in intravascular brachytherapy are much smaller than the conventional brachytherapy reference distance of 1 cm, it is recommended that
the reference distance for intravascular brachytherapy dosimetry be r 0 52 mm. In order to avoid confusion with TG-43
terminology, the following modified notation is recommended to generalize Eq. ~1!:
D ~ r, u ! 5S K L r 0 @ G ~ r, u ! /G ~ r 0 , u 0 !# g r 0 ~ r ! F ~ r, u ! ,
Medical Physics, Vol. 26, No. 2, February 1999
~5!
where L r 0 is the dose rate constant at a reference distance of
r 0 , and g r 0 is the radial dose function normalized to a radial
distance of r 0 and given by Eq. ~2! for a point source.
The radial dose function for intravascular brachytherapy
should be expressed with a reference point at 2 mm. Similarly, the dose rate constant L r 0 should also use the reference
distance of 2 mm i.e., it should be the dose rate at a reference
distance of 2 mm in water from a source of unit air kerma
strength. All relative dosimetric parameters such as g r 0 (r);
G(r, u ); and F(r, u ) should be measured for each specific
type and model of a delivery system. However, all users do
not have to measure these parameters as long as they have
verified the validity of the parameters used.
2. Dosimetry of catheter-based beta emitters
Because national standards for the air kerma strength of
beta-emitting sources do not exist, the AAPM recommends
that the dose at a point (r, u ) be determined using
D ~ r, u ! 5D ~ r 0 , u 0 !@ G ~ r, u ! /G ~ r 0 , u 0 !# g ~ r ! F ~ r, u ! ,
~6!
where D(r 0 , u 0 ) is the dose rate in water at the reference
point (r 0 , u 0 ). The reference point for intravascular brachytherapy calibration for beta sources should be r 0 52 mm and
u 0 5 p /2. All other quantities have the same meaning as in
the case of gamma emitters. For the calibration of betaemitting sources, i.e., the determination of D(r, 0 , u 0 ), the
method used by Soares et al.56 or an equivalent method,
should be used. Soares et al. measured dose rate averaged
over a 1 mm diam area from current measurements with an
141
Nath et al.: Intravascular brachytherapy physics
141
TABLE IV. The dose distribution of gamma emitter intravascular brachytherapy in coronary vessels.
Teirstein et al.
1995 ~Ref. 45!
Waksman et al.
1995 ~Refs. 32, 33!
Type of study
Type of catheter
Clinical trial
Non-self-centering
4 French
Isotope/form
192
Animal model
Non-self-centering
4 French in an
8 French
192
Ir ribbon, 3 mm
interseed center
spacing, 10 seeds
Author→
Nominal
prescription
dose
Normalized
prescription
dose
Dose at 2 mm
from centerc
Average,
minimum, and
maximum dose
at the vessel
surfacec
Average,
minimum, and
maximum dose
at 1 mm depthc
Average,
minimum, and
maximum dose
at 2 mm depthc
Average,
minimum, and
maximum dose
at 3 mm depthc
Ir ribbon, 4
mm interseed
center spacing,
nine seeds
8 Gy to the target
region the ~farthest
media point!
7.3 Gya
Weinberger’s
group 1994 ~Ref. 29!,
1995 ~Ref. 30!
Condado et al.
1995 ~Ref. 44!
Animal model
Non-self-centering
4 French in an
8 French
192
Ir ribbon, 5
mm interseed
center spacing,
five seeds
20 Gy to 1.5 mm
from the ribbon
center
19.7 Gy
Clinical trial
Non-self-centering
4 French
20–25 Gy to 1.5
mm from the wire
center
20–25 Gy
13.5 Gy
14.8–18.5 Gy
192
Ir wire
13.0 Gy
14 Gy to 2 mm
away, 0 mm along
the ribbon center
15.5 Gy ~14.11
Gy average in the
target!
15.5 Gy
17.0 Gy
14.7 Gy
18.2 Gy
19.8 Gy
15.5 Gy
21.6 Gy
17.6 Gy
13.9 Gy
20.2 Gy
20–25 Gy
9.3 Gy
7.4 Gy
9.8 Gy
10.7 Gy
8.1 Gy
11.7 Gy
9.3 Gy
7.0 Gy
10.3 Gy
11.7–14.7 Gy
N/Ab
N/Ab
6.2 Gy
4.8 Gy
6.7 Gy
7.2 Gy
5.3 Gy
7.9 Gy
6.1 Gy
4.5 Gy
6.7 Gy
8.2–10.2 Gy
N/Ab
N/Ab
4.6 Gy
3.5 Gy
5.0 Gy
5.2 Gy
3.9 Gy
5.8 Gy
4.4 Gy
3.2 Gy
4.9 Gy
6.2–7.8 Gy
N/Ab
N/Ab
a
An average distance of 3.2 mm from ribbon center to the farthest media point used as a dose prescription point.
N/A stands for not available.
c
Assuming a lumen diameter of 3 mm and exact source centering.
b
extrapolation ionization chamber with a graphite electrode.
In this case, the absorbed-dose rate to A150 plastic in Gy/s at
the surface of the plastic was given by
Ḋ ~ r, u ! 5
S D
33.9731.133B3U DI
1.1973A
Dd
,
~7!
0
where (DI/Dd) 0 5the rate of change of current ~normalized
to a reference temperature and pressure! with extrapolation
chamber air-gap thickness as the thickness approaches zero,
in units of nA/mm,
33.975the average energy in Joules needed to produce
one Coulomb of ions of either sign in air,
1.135the ratio of the mean mass stopping power of A150
plastic to that of air,
1.1975the density of air at the reference temperature and
pressure ~22 °C and 1 standard atmosphere! in kg/m3,
B5a correction for reduced backscatter from the collecting electrode, taken as 1.000,
U5a correction for attenuation by the high-voltage electrode, taken as 1.003, and
Medical Physics, Vol. 26, No. 2, February 1999
A5the area of the collecting electrode, measured with a
traveling microscope as 0.648 mm2.
The overall uncertainty in the calibration is estimated by
Soares to be 615%.
Finally, some guidance is given for converting from the
dose in A150 plastic to the dose in water or some other
medium. While A150 might not be the ideal choice for a
water- or tissue-equivalent material for beta particles, it does
have the advantage of being a conductor, and thus avoiding
the charge buildup problems characteristic of the high dose
rates possible from these sources. For point sources in infinite media, the dose at a distance r m corresponding to an
aerial density of r m r m ~in g/cm2! in the medium, D m (r m r m ),
is related to the dose in water, at the same aerial density,
r w r w , but scaled by78
D m ~ r m r m ! 5 h 3 ~ r m / r w ! 2 Dw ~ h r w r w ! ,
~8!
where h is the scaling factor of the medium relative to water,
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Nath et al.: Intravascular brachytherapy physics
142
TABLE V. The dose distribution of beta-emitter intravascular brachytherapy in coronary vessels.
Author→
Popowski et al.
1995 ~Ref. 59!, 1996 ~Ref. 60!
Type of study
Type of catheter
Animal model
Self-centeringa
Isotope/form
90
Nominal prescription
dose
18 Gy to 1.25 mm
from the wire
center
14.6 Gy
Dose at 2 mm from the
centerb
Dose at the vessel
surfaceb
Dose at 1 mm depthb
Dose at 2 mm depthb
Dose at 3 mm
depthb
Waksman et al. 1995 ~Ref. 37!
Animal model
Non-self-centering, 4.5 French in an
8 French
90
Sr/Y seeds to 5 mm length, five seeds
with 5 mm interseed center spacing
14 Gy to 2 mm from the seed center
Y wire
14 Gy
18 Gy
24.5 Gy
7.2 Gy
2.7 Gy
1.4 Gy
10 Gy
4.9 Gy
2.3 Gy
a
Catheter with a 2.5 mm diameter self-centering balloon.
Assuming a lumen diameter of 3 mm and exact source centering.
b
and r w and r m are the densities of water and the medium,
respectively. For A150 plastic, Soares et al.56 recommend
h 50.968 and r m 51.127 g cm23.
3. Recommendations on dose calibration of
catheter-based system
The AAPM recommends that the dose rate from a
catheter-based system using photon emitters be determined
using the dosimetry protocol described by AAPM TG-43,
with the modification that the reference distance be 2 mm
instead of the conventional reference distance of 1 cm. For
photon sources, the source strength should be measured in
terms of air kerma strength. The penetrating ability of the
radiation should be described by the radial dose function
normalized at 2 mm and its angular dependence by the anisotropy function.
For beta emitters in a catheter-based system, the AAPM
recommends the same protocol, except that the source
strength cannot be expressed in terms of air kerma strength.
Instead, the source strength in this case should be specified in
terms of the dose rate in water at a reference distance of 2
mm.
In order to develop a consistent set of specifications of
their equipment, manufacturers of catheter-based systems
should express the output in terms of a dose rate in water at
a distance of 2 mm, and use radial dose function and anisotropy functions over a distance of 10 mm to describe the dose
distribution around their products.
C. Dosimetric characterization of radioactive stents
Analogous to the previous case of catheter-based brachytherapy, analysis by the task group revealed a confusing variety of different dose specifications in radioactive stent implantation. Again, the task group undertook a major effort to
analyze all existing clinical studies of radioactive stents using a common framework. We chose a depth of 0.5 mm from
Medical Physics, Vol. 26, No. 2, February 1999
the surface of the stent as the reference depth and a total
treatment time of 28 days as a common framework for this
purpose. The 28 day period has also been the most commonly used time to sacrifice in the animal studies in this
area.
Dosimetry of the following four radioactive stent
studies37,79–81 were reviewed by the task group using a common approach that was selected to be the numerical integration model of Prestwich. The results of this evaluation are
shown in Table VI. The dose at 0.5 mm depth given in 28
days varies widely from 0.6 to 414 Gy in these studies,
which is not surprising because different activities were chosen deliberately by the investigators. The more interesting
observation is that the dose delivered per unit activity for the
same radionuclide varied by almost a factor of 4. The dose
normalized per mCi of 32P varied from 4.5 to 19.6 Gy/mCi,
indicating the effects of stent type, diameter, and length. In
most cases, the dose to 28 days was reported because that
was also the time to sacrifice. Direct comparison of dose
delivery by stent versus an acute catheter-based irradiation is
complicated because the dose rate effects are different. There
is some evidence that the dose delivered acutely more than
three days after angioplasty is not effective in reducing
neointimal proliferation. But it is not known whether this
applies to a continuous low dose rate delivered by stents. We
have arbitrarily chosen to tabulate the dose delivered in 28
days, recognizing that biological effects may correlate better
with other dose descriptors. Again, it is necessary to evaluate
dosimetry consistently from study to study so that meaningful conclusions can be made from clinical and preclinical
studies.
The location of the dose calculation point for intravascular brachytherapy must be specified differently for radioactive stents and catheter-based sources. The AAPM recommends that clinical prescription of radioactive stents should
be based upon the dose rate at a distance of 0.5 mm from the
143
Nath et al.: Intravascular brachytherapy physics
FIG. 17. Geometry conventions for dose rate calculations in the AAPM
TG-43 protocol. @Reprinted with permission from R. Nath, L. L. Anderson,
G. Luxton, K. A. Weaver, J. F. Williamson, and A. S. Meigooni, ‘‘Dosimetry of interstitial brachytherapy sources: recommendations of the AAPM
Radiation Therapy Committee Task Group No. 43,’’ Med. Phys. 22, 209–
234. Copyright 1995, American Association of Physicists in Medicine.!
surface of the stent. If the vessel diameter is 3 mm, for example, the dose calculation point for a catheter-based source
would typically be specified as 2 mm from the center of the
source. This same point would be 0.5 mm from the surface
of a radioactive stent, and should be specified as such.
Another question peculiar to a permanently implanted radioactive stent is that of treatment time. Since neointimal
hyperplasia in a stented artery occurs in the first few weeks
to two months after stent placement, only the dose delivered
during this period is effective. Hence, an effective treatment
time should be specified; 28 days is reasonable.
For the specification of the strength of radioactive stents,
the AAPM recommends that the activity, nominal diameter,
deployed diameter, length, type, and model be specified for
each individual case. It is also recommended that doses radial to a stent can be calculated using beta point dose kernels. The axial dependence of the dose at a fixed radial distance can be calculated by the cylindrical shell method of
Prestwich et al.63 and Duggan et al.66 for a uniform distribution of 32P on the outside of the stent, and Janicki et al.67 for
the Palmaz–Schatz geometry ~Figs. 13–14! or the advanced
stent design model.68 All of these dose models, except for the
latter, have been verified by radiochromic film dosimetry.
A difficulty with determining the activity and consequently calculating the dose of a 32P stent is the necessity
that the stent remain sterile for patient use. The stents are
shipped in a Plexiglas safety cylinder with sufficient wall
thickness to absorb all the beta particles. Although the beta
particles are absorbed within the Plexiglas walls of the shipping container, bremsstrahlung x rays are produced. Larsen
and Mohrbacher82 have reported a technique to determine
32
P activity by bremsstrahlung counting methods. The
bremsstrahlung x rays detected are directly proportional to
the number of betas emitted. Also, it is assumed that no other
contaminating radionuclides are present in the sample.
In preliminary experiments, Coffey and Duggan65 have
demonstrated that a NaI~Tl! scintillation crystal and a multiMedical Physics, Vol. 26, No. 2, February 1999
143
channel analyzer ~MCA! can be used to count bremsstrahlung x rays from low activity 32P stents. Early experiments
indicate that individual determinations of the activity of each
stent can be achieved to an accuracy of 610% while maintaining sterility.
The source activity of mixed beta-gamma emitters may be
conveniently measured by counting the gamma photo peak
in standard geometry, with a possible correction for the
bremsstrahlung continuum if necessary. In the case of a positron emitter such as 48V, the 511 keV annihilation photons
provide another simple solution. Because the maximum beta
energy for 48V is only 696 keV, bremsstrahlung makes no
significant contribution at 511 keV, and absolutely none at
the strongest gamma energy of 1.15 MeV ~100%! of 48V, so
activity can easily be determined with a calibrated detector
with a lower-energy threshold, just including the 511 keV
photo peak, or even in a calibrated ionization well chamber
in a beta-absorbing plastic shield. The small gamma contribution to the dose distribution may be calculated using a
point dose kernel integration, but the beta dose distribution is
best calculated using a Monte Carlo technique that can properly account for absorption of the emitted betas within the
metallic stent material. This is more important for the proton
activated 48V stent because its activity is distributed throughout the stent metal and has a relatively low energy compared
to the higher-energy betas from 32P distributed only on the
stent outer surface.
NIST does offer a reference standard 32P source for activity analysis. The user can use a number of relative calibration
procedures including a well-type ionization chamber,83 an
NaI~Tl! scintillation counter, or a liquid scintillation counter.
For the particular counting method chosen, a calibration factor traceable to NIST must be available. The NIST standardization process utilizes a high efficiency liquid scintillation
counting method. Solutions standardized by this technique
may then be used to establish the counting efficiencies for
various practical sample geometries for reentrant ionization
chamber dose calibrations and NaI~Tl! photon counters.
These very practical transfer techniques are exceedingly useful for relative measurements, but standards are needed to
first calibrate the instrument.84 An unacceptably large error
may be encountered if one compares sources of different
geometries in these ‘‘secondary instruments.’’
D. Recommendation of clinical prescription and dose
reporting of radioactive stents
The measurement of dose distributions in close proximity
to a radioactive stent is a monumental task, which need not
be repeated for each clinical case. Instead, reasonably consistent treatments can be achieved by specifying the activity
implanted in a given stent model provided the geometry is
carefully reported. Therefore, the AAPM recommends that
for each type of radioactive stent the three-dimensional dose
distributions around stents of various lengths, diameters, and
activities should be carefully determined by benchmark dosimetry studies before clinical implementation. Also, it is
recommended that for each radioactive stent procedure the
144
Nath et al.: Intravascular brachytherapy physics
activity of the stent, its nominal diameter, deployed diameter,
length, type, and model be used for a clinical prescription,
and doses delivered at a depth of 0.5 mm from the surface of
the stent in the midplane and over a time period of 28 days
should be reported for treatment and evaluation. Although
the dose to full decay and the dose over several time periods
is important for a full evaluation of biological and clinical
results, the task group recommends a dose accumulated over
28 days as a common reference time. Even for different radionuclides of varying half-lives, most animal studies in this
field use 28 days as the time to sacrifice for endpoint evaluation.
E. Quality assurance and safety aspects
A comprehensive quality assurance ~QA! program is required for intravascular brachytherapy to assure consistency,
accuracy, and safety of the personnel involved. Several reports on QA for conventional brachytherapy exist in the
literature.85–89 In this section we describe QA aspects as they
relate to intravascular brachytherapy procedures. Specifics of
a QA program depend to an extent on the technique utilized
in intravascular irradiation. Four major techniques being explored at present are ~1! manually loaded sealed sources; ~2!
remotely loaded sealed sources; ~3! radioactive stent placement; and ~4! radioactive liquid balloons. Essential elements
of a comprehensive QA program for each of the above techniques, except for radioactive liquid balloons, are described
below. For radioactive liquid balloons, there is insufficient
information in the literature to recommend a quality assurance program. For the first three techniques the following
items should be part of a QA program.
~1! Document in detail the essential properties ~radiation and
physical! of the radioactive source.
~2! Develop protocols to be followed for the purchase and
receipt of sources in collaboration with the institution’s
radiation safety officer ~RSO!. For remotely loaded
sources, develop acceptance testing and commissioning
procedures.
~3! Develop guidelines to safely store the radioactive
sources and control their access and perform periodic
inventory of the sources and enter the results in log
books.
~4! Check the physical integrity of the sealed sources prior
to use and perform leak tests. Remotely loaded sources
require an extensive routine QA procedure, which includes ~1! room safety interlocks; ~2! lights and alarm
functions; ~3! console functions ~including audio/visual!;
~4! switches and batteries; ~5! visual inspection of source
guides; ~6! accuracy of the source preparation using an
autoradiograph; ~7! source positioning accuracy ~dummy
loading and real source loading!; ~8! the timer function;
~9! calibration of source activity; ~10! mechanical integrity of the applicators; and ~11! emergency response. Details of these procedures have already been
described.85–89
Medical Physics, Vol. 26, No. 2, February 1999
144
~5! Develop a methodology to verify source activity using
in-house equipment such as dose calibrators, reentrant
chambers, etc.
~6! Develop methods to properly sterilize sources when required. Open-ended afterloading catheters employed in
intravascular irradiation come in contact with patient’s
body fluid and hence require sterility.
~7! Develop protocols to safely transport radioactive material from a room to a sterilization department and then
onto a catheterization room.
~8! Develop the protocol to safely dispose of the sources
after the procedure or to store the unused sources on site.
~9! Assure all the needed ancillary equipment ~e.g., long forceps, stopwatch, scissors, etc.! are readily available on a
tray at the time of the irradiation procedure.
~10! Develop protocols to be followed in case of unexpected
emergencies. Some urgent instances are ~1! source
breakage and contamination; ~2! loss of a source within
vasculature of the patient; ~3! loss of a source in the
catheterization room; ~4! cardiac or respiratory arrest
~related or unrelated to the irradiation procedure!; and
~5! emergency surgery. All emergency procedures
should be coordinated with the RSO. For example, an
emergency lead container must be present in the room
during the entire procedure for use by physicists/RSO.
~11! Develop a protocol that describes the role of each individual in this interdisciplinary procedure. A working
team for intravascular irradiation protocol must include
~1! an interventional cardiologist or radiologist; ~2! a
radiation oncologist; ~3! a radiotherapy physicist; ~4! a
health physicist; and ~5! a nurse/coordinator. Each individual should know the role he/she is expected to
fulfill during this procedure. The duties of the health
physicist in this procedure may be assigned to the radiotherapy physicist.
~12! Develop a form for the dose prescription ~written directive! to be filled by the authorized user prior to the
initiation of irradiation.
~13! Develop and document the dosimetric methods employed in computing the irradiation time. The calculation should be independently verified and signed prior
to initiation of the procedure.
~14! Verify that the correct sources chosen for irradiation
and that all treatment planning parameters used correspond to that patient.
~15! Monitor radiation levels around the patient/room during
the procedure.
~16! Perform and document radiation protection surveys at
the end of the procedure as mandated by state/federal
regulations.
~17! For permanent implants of a radioactive stent, the patient needs to be given a complete instruction on safety
and follow-up aspects. This is normally accomplished
at the time of patient discharge.
~18! Develop a program to routinely provide education and
training on radiation protection to all the staff members
145
Nath et al.: Intravascular brachytherapy physics
145
TABLE VI. Dose evaluation of stent experiments in animals.
Investigator
Hehrlein et al.
1995 ~Ref. 38!
Hehrlein et al.
1995 ~Ref. 38!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Carter et al.
1996 ~Ref. 80!
Hehrlein et al.
1996 ~Ref. 81!
Hehrlein et al.
1996 ~Ref. 81!
Laird et al.
1996 ~Ref. 39!
Rivard et al.
1996 ~Ref. 79!
Stent
type
Length
Diameter
Isotope
Activity
Biological endpoint
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Palmaz–
Schatz
half-stent
Modified
Strecker
7.5
mm
3.0 mm
Mixed
17.5 mCi
7.5
mm
3.0 mm
Mixed
35 mCi
7 mm
3.5 mm
~assumed!
32
0.15 mCi
7 mm
3.5 mm
~assumed!
32
0.5 mCi
7 mm
3.5 mm
~assumed!
32
1.0 mCi
7 mm
3.5 mm
~assumed!
32
3.0 mCi
7 mm
3.5 mm
~assumed!
32
6.0 mCi
7 mm
3.5 mm
~assumed!
32
14 mCi
7 mm
3.5 mm
~assumed!
32
23 mCi
7.5
mm
3.0 mm
32
4 mCi
7.5
mm
3.0 mm
32
13 mCi
20
mm
5.0 mm
32
0.14 mCi
Palmaz–
Schatz
half-stent
7.5
mm
3.5 mm
~assumed!
32
0.6 mCi
Neointimal
thickening in
rabbit iliac artery
Neointimal
thickening in
rabbit iliac artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in pig
coronary artery
Neointimal
thickening in
rabbit iliac artery
Neointimal
thickening in
rabbit iliac artery
Neointimal area
in pig iliac
artery
Mean area
stenosis index in
pig RCA
P
P
P
P
P
P
P
P
P
P
P
involved, including physicians, nurses, and ancillary
personnel.
VII. SUMMARY OF RECOMMENDATIONS
~1! The source strength of a catheter-based system should
be expressed in terms of the air kerma rate in air for gamma
sources ~air kerma strength! and the dose rate in water at a
reference distance of 2 mm for beta emitters.
~2! Dose distributions around a catheter-based brachytherapy source should be determined using the AAPM Task
Group No. 43 protocol for photon sources and a modified
version of the AAPM Task Group No. 43 protocol for beta
sources.
~3! The source strength of a catheter-based system should
be traceable to a national standard at NIST or at an ADCL.
~4! The radial dose function, geometry function, and anisotropy function should be determined for each specific
Medical Physics, Vol. 26, No. 2, February 1999
Time to
Sacrifice
~days!
Dose in 28 days at
the distance
28, 84,
364
10 Gy from 0 to 1 mm
28, 84
20 Gy from 0 to 1 mm
28
2.7 Gy at 0.5 mm;
1.5 Gy at 1 mm;
0.49 Gy at 2 mm
9.0 Gy at 0.5 mm;
4.9 Gy at 1 mm; 1.6
Gy at 2 mm
18.0 Gy at 0.5 mm;
9.7 Gy at 1 mm;
3.3 Gy at 2 mm
54.0 Gy at 0.5 mm;
29.2 Gy at 1 mm;
9.9 Gy at 2 mm
107.9 Gy at 0.5 mm;
58.4 Gy at 1 mm;
19.7 Gy at 2 mm
251.9 Gy at 0.5 mm;
136.4 Gy at 1 mm;
46.1 Gy at 2 mm
413.8 Gy at 0.5 mm;
224 Gy at 1 mm;
75.7 Gy at 2 mm
78.4 Gy at 0.5 mm;
42.2 Gy at 1 mm;
14.2 Gy at 2 mm
254.7 Gy at 0.5 mm;
137.3 Gy at 1 mm;
46.2 Gy at 2 mm
0.63 Gy at 0.5 mm;
0.35 Gy at 1 mm;
0.12 Gy at 2 mm
10.1 Gy at 0.5 mm;
5.5 Gy at 1 mm;
1.9 Gy at 2 mm
28
28
28
28
28
28
28, 84
28
28
21
source design of a commercial catheter-based system.
~5! The clinical prescription for a catheter-based system
should be expressed in terms of the dose delivered at a reference depth in water.
~6! For a catheter-based system, the depth of dose prescription for intracoronary applications should be at a radial
distance of 2 mm from the center of the source and for peripheral vessels 2 mm larger than the average lumen radius.
An average lumen radius should also be reported.
~7! For optimal assessment of each clinical case, average,
minimum, and maximum doses delivered should be estimated in at least three planes perpendicular to the catheter
and along its length.
~8! The output of all commercial intravascular brachytherapy catheter-based systems should be specified in terms
of the dose rate in water at a radial distance of 2 mm from
the center of the catheter.
~9! The penetrating ability of all commercial intravascular
146
Nath et al.: Intravascular brachytherapy physics
brachytherapy catheter-based systems should be specified in
terms of the radial dose function normalized at a distance of
2 mm and at radial distances from 0.5 to 10 mm ~or R 90 ,
90% of the electron range for beta emitters!, at 0.5 mm intervals, with a reference depth of 2 mm.
~10! Uniformity of the dose delivered by catheter-based
systems at points both along the source axis, at r52 mm,
and around the circumference of a 2 mm radius circle centered on the source axis in a plane perpendicular to it should
be better than 610% ~the range of values from minimum to
maximum in the centered two-thirds of the treated length of
at least 3 cm along the catheter axis!.
~11! For each catheter-based system, an atlas of threedimensional dose distributions should be generated to estimate the dose variation in the target.
~12! The clinical prescription of radioactive stents should
be in terms of ~1! stent diameter, nominal and deployed; ~2!
stent length; ~3! stent type, brand, model; ~4! radioisotope;
and ~5! activity.
~13! The measured activity of a radioactive stent should
be traceable to a national standard at NIST.
~14! Activity for each radioactive stent to be used should
be determined using an appropriate transfer technique.
~15! For radioactive stents, doses at 0.5 mm radial distance from the surface of the stent in the midplane and over
time periods of 28 days should be reported.
~16! The quality assurance program presented in this
AAPM task group report should be followed under the direction of a qualified medical physicist.
VIII. FUTURE CONSIDERATIONS
One of the controversies in the current literature is regarding the optimal choice of a radionuclide for a catheter-based
system. The ideal catheter-based source would have high activity in a small volume, long half-life ~to reduce the cost!,
uniform dose over treatment distances of 2–3 mm from the
source center, and a low cost. No available isotope is ideal.
Beta emitters such as 32P and 90Sr/90Y have advantages in
terms of high activity and dose rate, radiation safety, and
half-life; while gamma emitters such as 192Ir have advantages
in terms of radial dose uniformity, high dose rate, and reasonably long half-lives. Each isotope could be fabricated at
the required activities and size using the current technology.
There is a tradeoff between the increased radial range of
gamma emitters and the safety advantages of beta emitters.
Because of the large amount of shielding required and the
high activity for gamma emitters, it is possible that safety
considerations may require that gamma emitters be used only
with specially shielded remote controlled units. Beta emitters, on the other hand, may be usable via hand loaded techniques, thus reducing the cost. The choice of beta versus
gamma should ultimately depend upon the results of clinical
studies and the task group was unable to come to a consensus
regarding the optimum radionuclide.
Another controversial question was regarding the need for
centering in a catheter-based system. The answer to this
question would depend upon the choice of radionuclide and
Medical Physics, Vol. 26, No. 2, February 1999
146
on the biological window of therapeutic efficacy without
normal tissue toxicity. It appears, for example, that a minimum dose on the order of 8–16 Gy to a depth of 0.5 mm into
the vessel wall is required to prevent restenosis. The maximum vessel tolerance dose is not well known but can be
speculated to be on the order of 32 Gy to the surface of the
vessel wall. These limits imply that dose uniformity within
the target region must be within a factor of 2–4. The normal
vessel wall thickness is on the order of 0.5 mm, and it is
possible that all sections of the vessel wall need to be treated
in order to prevent restenosis. Also, the diseased vessels
could have thicker walls. Assuming a treatment wall thickness of 0.5 mm, even for a perfectly centered source, the
dose variation to the various sections of the vessel wall ~say,
from radial distances of 1.5–2.0 mm! will be on the order of
50%–70%. Again, the answer to the question regarding the
need for centering will have to wait for the completion of
clinical investigations.
There are a number of other important questions that the
task group could not resolve at this time. Some of them are
~1! recommendations about the accuracy desired of the
source calibration under standard conditions, ~2! the accuracies of various calibration methods, ~3! the expected accuracy of the dose delivered under clinical conditions, ~4! a
comparison of the clinical efficacy of catheter-based brachytherapy, radioactive stent implantation, and radioactive liquid balloons, ~5! the consideration of the dose rate effects in
the use of various modalities for intravascular brachytherapy,
~6! consideration of the effects of contrast media, metallic
stents, and plaque composition on the dose distribution produced by various forms of intravascular radiotherapy, and ~7!
recommended values for dosimetry parameters for each of
the commercial systems. All of these issues should be addressed by scientific and clinical investigators in this field.
The AAPM will continue to monitor scientific progress in
this area and make further recommendations at an appropriate time in the near future.
ACKNOWLEDGMENTS
The authors thank Deanna Jacobs for preparing and editing this manuscript. Marc Miner at Emory University helped
clarify the dosimetric calculations used in the Emory University studies. Dr. Prestwich provided the details of his numerical model, which allowed us to compare the dosimetry of
stents. Some of the work reported here was supported in part
by a USPHS Grant No. R01-HL58022-01 ~R. Nath, principal
investigator! from the National Heart, Blood and Lung Institute.
APPENDIX: CORONARY AND PERIPHERAL
VASCULAR INTERVENTIONS GLOSSARY
Acute gain
Change in minimum lumen diameter ~MLD! following stent insertion, usually expressed in millimeters.
147
Nath et al.: Intravascular brachytherapy physics
Adventitia
Angiogram
Angiography
Arteriosclerosis
Atherectomy device
Atheroma
Atherosclerosis
Balloon catheter
Balloon expandable
Balloon profile
Calcification
Cannulation
Catheter
Catheter lumen design
The outermost layer of the coronary artery.
An image of a blood vessel. Specifically, an x-ray image of blood
vessels filled with contrast media;
a cine angiogram is a 35 mm
movie consisting of angiograms
of the coronary arteries, typically
obtained at a rate of 30 frames per
second.
The procedure used to obtain an
angiogram.
Thickening, hardening, and loss
of elasticity of the arterial wall.
A catheter equipped with a cutting tip for removing atherosclerotic plaque, often as a precursor
to balloon angioplasty and/or
stent placement.
A thickening and fatty accumulation within the arterial wall.
A form of arteriosclerosis characterized by focal atheromas.
A catheter with a balloon at the
distal tip for performing angioplasty or delivering intracoronary
stents. Separate lumens provided
for a guide wire and for injecting
fluid to inflate the balloon are
typically accessed via an integral
manifold, although in some cases
separate ports are provided. Standard balloon catheters are 135 cm
in length from the tip to the manifold strain relief. One ore more radiopaque markers is provided for
visualization of the balloon for
placement across the lesion.
A type of stent that is delivered on
a balloon catheter.
The diameter of the deflated balloon on a balloon catheter.
Calcium deposition within the arterial wall.
Insertion of a tube into an orifice.
A hollow tube designed to be
passed through various canals/
orifices.
Refers to the method for providing separate lumens for balloon
inflat-ion and a guide wire,
e.g.,coaxial ~tube within a tube!,
dual lumen, or triple lumen. Balloon catheters of-ten have a
‘‘monorial’’ design for the guide
wire lumen, which is coaxial in
the distal portion, but exits
through the side of the catheter
Medical Physics, Vol. 26, No. 2, February 1999
147
Catheter shaft
Cine
Collateral
Compliance
Conformability
Coumadin
Crossability
Deflation time
Diastole
Diffuse
Distal
Eccentric
ECG
Embolism
Embolus
Endarterectomy
within the guide catheter to facilitate balloon catheter exchange
without the need for an exchange
or extension wire.
The main body of a catheter.
Shaft material affects conformability, tractability, and pushability.
Denoting movement related to
film.
A vessel connecting two arteries,
providing alternate routes for
blood flow.
The ability of a balloon material
to stretch in relation to applied
pressure.
The ability of a balloon to take
the shape of the artery.
Oral anticoagulant medication.
Ease with which a balloon or
other device can be placed
through a stenosis. Related to profile, pushability, sliding mechanics, and conformability.
Time required to deflate an angioplasty balloon. Influenced by inflation lumen size and balloon capacity. Short deflation times
reduced ischemic time.
The part of the cardiac cycle in
which the ventricles are dilating,
filling with blood.
Spreading, scattered.
Farthest from the center of the
point of reference. When referring
to catheters, the reference point is
the angiographer, so the distal end
of the catheter is inserted into the
patient. When referring to coronary arteries, the reference point
is the coronary ostium, so the normal direction of blood flow is
from proximal to distal.
Situated or occurring away from
the center. Off center. Noncircular.
The abbreviation of an electrocardiogram; a graphic record of the
heart’s electrical activity.
The sudden blocking of an artery
by a clot or foreign material that
has been brought to its site of
lodgment by the blood current.
A clot or other plug brought by
the blood from another vessel and
forced into a smaller one, thus obstructing the circulation.
Surgical excision of the thick-
148
Nath et al.: Intravascular brachytherapy physics
Endothelium
Exchange wire
Extension wire
External elastic lamina
Femoral
Flexibility
Formability
French ~scale!
Free wire movement
Gradient
Guide wire
ened, atheromatous intima of an
artery.
A single layer of flat cells that line
any vascular lumen.
A guide wire long enough ~300
cm! to allow an entire balloon
catheter to be withdrawn from the
patient onto the wire external to
the patient without withdrawing
the wire.
A length of wire that can be attached to the proximal ~external!
end of a standard 175 cm guide
wire so that it can be used as an
exchange wire.
The structural membrane separating the media from the adventitia
of an artery.
Relating to the femur or the thigh,
e.g., the femoral artery, a common
arterial access site for performing
angiography and angioplasty procedures.
The ease with which a guide wire
or catheter can bend to negotiate
tortuous anatomy.
The provision of a short segment
at the distal tip of a guide wire
that may be shaped by the operator to facilitate maneuvering
through specific anatomy.
A unit for the diameter of a catheter or introducer. 1 French is 1/3
mm.
The desirable ability of the guide
wire to slide easily within a balloon catheter.
The change of various functions,
i.e., pressure, temperature, etc.
A flexible, steerable wire placed
through the guide catheter into the
coronary artery and across the lesion to serve as a guide over
which the balloon catheter is
pushed. The distal 20–30 cm are
typically radiopaque, and the distal tip may be formable or have a
permanently bent segment ~‘‘J’’
tip! to facilitate steering. Standard
short guide wires are at least
175cm long. Long guide wires, or
exchange wires, are 300 cm long.
Guide wire diameters are specified in inches, typically from
0.010 in. to 0.018 in. 0.002 in. increments. The wire diameter and
construction determine torquabil-
Medical Physics, Vol. 26, No. 2, February 1999
148
Guiding catheter
Hemodynamic
Hemostasis
Hemostatic valve
Heparin
Hypotube
Infract, infarction
Internal elastic lamina
Intima
Introducer ~sheath!
Ischemia
IVUS
LAD
ity and compatibility with various
balloon catheter systems.
A large inner diameter single lumen angiography catheter through
which a guide wire and balloon
catheters are passed, and through
which contrast injections are
made for visualizing the artery.
The guiding catheter is advanced
only as far as the coronary ostium.
Standard guiding catheters are
100 cm long with outer diameters
of 6–10 F.
Pertaining to the movements involved in the circulation of blood.
The control of blood flow or
bleeding.
A valve at the proximal end of the
guide catheter to prevent arterial
pressure from ejecting blood back
through the lumen. The valve is
designed to allow a guide wire
and/or balloon catheter to be
passed through it.
Injectable anticoagulant medication, typically used to reduce clotting in catheters, introducers, etc.,
during angioplasty procedures.
A stainless steel hollow tube. Hypotube is often used for the proximal segments of guide wires and
catheter shafts.
An area of tissue death and scarring due to ischemia.
The structural membrane separating the intima from the media.
The layer of a blood vessel wall
inside the internal elastic lamina,
composed of a single layer of endothelial cells in normal coronary
arteries.
A short tubular device placed
through the skin into the artery to
provide arterial access. The guide
catheter must make a tight seal
against the lumen of the introducer to maintain hemostasis.
A deficiency of blood to themyocardium. Prolonged severeischemia can lead to myocardial infarction. Ischemia can be caused
by constriction or actual obstruction of a coronary artery due to
coronary artery disease or due to
the presence of a PTCA balloon
or other intracoronary device.
Intravascular ultrasound.
Left Anterior Descending coro-
149
Nath et al.: Intravascular brachytherapy physics
LCA
LCX or CFX
Laser catheter
Lesion
Lumen
Manifold
Media
MLD
Myocardium
Myocardial infarction
~MI!
Net gain
Nominal balloon size
nary artery. One of the two main
branches of the LCA. Usually
serves the anterior 32 of the left
ventricle, including the apex, and
part of the interventricular septum.
Left Coronary Artery. Bifurcates
within 1–2 cm of its ostium into
the LAD and LCX.
Left Circumflex coronary artery.
One of the two main branches of
the LCA. Usually serves the lateral wall and one-half of the posterior wall of the left ventricle,
and the left atrium.
A catheter containing a fiber-optic
channel for delivering highintensity laser energy to increase
MLD by vaporizing atherosclerotic plaque, usually followed by
balloon angioplasty and/or stent
placement.
A pathological change in tissue;
wound or injury.
The space in the interior of a tubular structure, such as an artery
or the intestine.
A connector at the proximal end
of a catheter with one or more
ports communicating with each of
the catheter’s lumens. The simplest manifold is a ‘‘Y adapter’’
that provides two ports into a
single lumen: a straight through
lumen for passing a guide wire or
other catheter, and a second,
angled, port for injecting or withdrawing fluids such as contrast
material or heparinized saline.
Muscular layer of the arterial
wall.
Minimum lumen diameter at the
site of a stenosis, usually expressed in millimeters.
The muscular tissue of the heart.
Prolonged severe ischemia that
re-sults in necrosis ~death!
ofmyocar-dium. The result of
coronary occlu-sion from thrombus formation or spasm at the site
of an atheroma.
The change in MLD at long term
angiographic follow-up.
The manufacturer’s specified balloon diameter, in millimeters,
reached at the nominal inflation
pressure, specified in atmospheres.
Medical Physics, Vol. 26, No. 2, February 1999
149
Occlusion
Opacification
Ostium
Patent
Plaque
Proximal
PTCA
Pushability
Radiopacity
Radiopaque
Rated burst pressure
RCA
Restenosis
A total blockage of an artery to
blood flow.
Making an artery or balloon
opaque to radiation by the introduction of a contrast medium
A general term to designate an
opening into a tabular organ. The
origin of a coronary artery in the
aortic root.
Open to blood flow, unobstructed,
not closed.
A patch or small differentiated
area on a body surface. Arteries
can become obstructed with atherosclerotic plaque.
Closest to the point of reference.
When referring to catheters, the
reference point is the angiographer, who holds the proximal end
of the catheter while the distal end
is inserted into the patient. When
referring to arteries, the reference
point is the ostium, so a balloon
catheter approaches a lesion from
the proximal side.
Percutaneous—through the skin,
transluminal—through the lumen
of a vessel, coronary pertaining to
the heart, angioplasty repair of a
blood vessel. Usually synonymous with balloon angioplasty.
The ability of the catheter shaft to
transfer the force from the proximal end of the shaft to the distal
tip so that the balloon or other device can be advanced through the
vessel and across the stenosis.
The extent to which a catheter,
wire, stent, or other device absorbs x rays, making it visible in
an x-ray image.
Impenetrable to an x ray or other
forms of radiation.
The maximum pressure the manufacturer recommends for inflatingan angioplasty or stent delivery
bal-loon, typically specified in
atmo- spheres. The label recommends that the RBP should not be
exceeded.
Right Coronary Artery. Serves the
inferior wall of the left ventricle,
parts of the right ventricle and interventricular septum, the right
atrium, and may serve the left
ventricular apex in some people.
Recurrence of a stenosis after a
corrective procedure.
150
Nath et al.: Intravascular brachytherapy physics
Rotoblator: rotating
atherectomy device
Self-expanding
Sheath
Sliding mechanics
Slotted tube
Stasis
Steerability
Stenosis
Stent recoil
Systole
Thrombolysis
Thrombolytic
Thrombus
Torque response
Tortuous
A form of endarterectomy device
consisting of a catheter equipped
with a high-speed rotating abrasive burr at the tip for removal
~ablation! of tissue to increase arterial MLD often followed by balloon angioplasty and/or stent
placement.
A type of stent that expands in the
artery without use of a balloon
catheter.
Introducer sheath. See ‘‘Introducer.’’
The extent to which a balloon
catheter slides smoothly within
the guide catheter or through the
coronary artery. Good sliding mechanics are enhanced by a low
profile balloon and small diameter
shaft used in a large lumen, kink
resistant guide catheter, and the
use of lubricating coatings.
A stent manufacturer by cutting
longitudinal slots in a solid tube
of metal.
A stoppage or diminution of the
normal flow of blood or other
body fluid within a body part.
The ease with which a guide wire
can be maneuvered through desired arterial branches. Related to
the torque response and flexibility.
Narrowing or stricture of an artery, such as that caused by atherosclerotic plaque and/or an intracoronary thrombus.
The fractional reduction of a stent
diameter when the delivery balloon is deflated, defined as the diameter of the expansion balloon
minus MLD after stent placement,
divided by the diameter of expansion balloon.
The part of the cardiac cycle
whenthe ventricles are contracting,expelling blood.
The phenomenon by which preformed thrombi are dissolved.
Dissolving or splitting up a
thrombus.
Blood clot.
The response at the distal tip of a
guide wire or other device to the
angiographer’s twisting the proximal end.
Referring to a vessel with many
Medical Physics, Vol. 26, No. 2, February 1999
150
Trackability
Trans-stenotic gradient
Y adapter
a!
short radius bends, like a winding
road.
The ease with which the balloon
catheter or other device can be advanced over a guide wire through
tortuous
coronary
anatomy.
Trackability is generally best for
catheters with a small, flexible,
coaxial distal shaft and good sliding mechanics.
Pressure difference across a
stenosis.
A connector for the proximal end
of a catheter providing two ports
into the catheter’s central lumen:
a coaxial ‘‘thru’’ port for a guide
wire or other device; and an
angled port for fluids. Y adapters
often also include a rotating hemostatic valve.
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