Comparison of MCNP4B computer simulation to radiochromic film studies of an Iridium-192 brachytherapy sourcewire

Tony DiMauro, Paul Pater, and Patrick Papin
Department of Physics, San Diego State University
San Diego, California 92182
Jennifer Stratford
Department of Medical Physics & Biomedical Engineering, Southampton General Hospital
Southampton, UK S016 6YD
J. Scott Langford
Environmental Health and Safety, University of California at San Diego
San Diego, California 92093

Abstract

This work provides dosimetric data for a high dose rate Iridium-192 source currently under clinical trials by the FDA. This iridium source was developed for use in a remote afterloading system for Intravascular Brachytherapy treatments. The source is 4.5 cm long with a diameter of 0.571 mm. Analytical Monte Carlo (MCNP4B) computer simulations incorporating detailed source construction and dimensions along with in-house calibration and exposure of radiochromic film were utilized to produce dosimetry calculations around the iridium source. Two different catheters were used in this study; a platinum coated catheter and a standard catheter. Measurements were made of the dose rate as a function of radial distance from the center of the sourcewire out to 5 mm. The standard catheter film exposure measurements did not verify the computer simulation data near the sourcewire. The computer simulation data was in close agreement with the film study measurements from 1 to 5 mm. For the platinum coated catheter, the film study measurements and computer simulation data are in virtual agreement to within 1% error from the sourcewire out to 5 mm. Comparing the radial dose rate distribution for a platinum coated catheter and a standard catheter confirmed the computer simulation data and demonstrates that the radiochromic film has a characteristic under response due to low-energy electrons. The platinum filtered catheter provides the irradiated vessel wall with a more linear dose rate. The standard catheter provides the irradiated vessel wall with a more non-linear dose rate. This paper shows that the low-energy electrons originating in the Iridium-192 source contribute significantly to the dose at short distances from the source.

I. INTRODUCTION

Intravascular brachytherapy for the treatment of restenosis (IVBT) requires accurate dosimetry within a few millimeters(1). This requirement is unlike the centimeter dosimetry demands required by conventional brachytherapy. Since early treatments utilizing such sources as Iridium-192 and Cesium-137, the accuracy of the dosimetry has become a major issue. Developing an acceptable sourcewire and source geometry for use in intravascular brachytherapy is an ongoing research pursuit(2). The perfect radioisotope would exhibit the following properties: 1) low-dose gradient within 5 mm from the center of the source, 2) acceptable low-dose levels surrounding adjacent tissues and organs, 3) very low radiation exposure levels around the patient and clinical staff, 4) treatment time less than 10 minutes for delivering approximately 10 Grays, and 5) sources with an intermediate half-life are also desirable to facilitate the management of sources and waste.

The first trial using Iridium-192 radioactive seeds for the treatment of atherosclerotic plaques was conducted by Condado et al.(3) in Venezuela. These early trials employed catheter-based treatments utilizing the AngioRad iridium source (Interventional Therapies LLC Systems)(4). This system has also been employed and evaluated in the Artistic I trial5 which sought to demonstrate its safety and efficacy in decreasing the recurrence of restenosis in a previously stented lesion. The structure and dimensions of this source differ significantly from other available sources in its uniquely small diameter. The narrowness of this source will allow for significant blood profusion reducing patient discomfort during treatment. Insertion into small vessels requires accurate dosimetry to avoid excessive dose that may result in possible adverse effects and potential misadministration(6). Dosimetry at distances within a millimeter from radioactive sources is difficult to determine and generally poorly known. In traditional brachytherapy, the dose is typically specified at 1 cm from the source and effects of low energy photons and secondary electrons are mostly ignored. With intravascular brachytherapy, however, the target dose may be 1-3 mm. To understand the results of a variety of radionuclides and delivery systems, it is essential to determine the dosimetry from all particle and photon emissions in the millimeter range(7).

Utilizing both MD-55-2 GafChromic™ film(8) and MCNP4B computer simulation code (9) we have examined the dose distribution around this catheter-based source. This study will demonstrate that the beta and atomic electron contribution to the dose is significant near the sourcewire. Experiments were conducted using a standard catheter and a platinum-coated catheter. The platinum coating will demonstrate the magnitude of the electron dose to tissue. The GafChromic film is utilized since it is the preferred dosimeter in areas of high dose rate gradient brachytherapy sources. The MCNP4B simulation code yields three dimensional analytical dosimetry calculations and reduce uncertainties near the source. AAPM Task Group 43 and Task Group 60 formalism(10) were not implemented in this paper notwithstanding an eventual need of standardization. Also, the authors note the fact that this source has at least one dimension that cannot be considered small compared to the distances of therapeutic interest and/or the mean-free path of the emitted radiation. Within itself may pose Task Group problems.


II. MATERIALS AND METHODS


A. Radioactive source

   The AngioRad™ Afterloader System is a unique 4.5 cm long Iridium-192 source which is encapsulated at the end of a 150 cm nickel-titanium wire (see Fig. 1). The iridium core is 118.5 mm in diameter and is covered by a 3.0 mm thick layer of titanium sealed in a cylindrical wire of nickel-titanium 345.5 mm in outer diameter. The length-to-diameter ratio of the source geometry is approximately 380 which is unusually high in comparison to most sources. The activity of the sourcewire used in this study was determined by AngioRad™ and traceable to NIST (National Institute of Standards).
    Iridium-192 has a complex radiation emission spectrum (11). The total average photon energy per disintegration is 813 keV, and the average photon energy is 347 keV. The total average atomic energy per disintegration is 45.2 keV. There is also a continuous spectrum of beta particles with a total average energy of 170 keV per disintegration. Most recent work demonstrates that not only secondary electrons, but also beta particles originating in the Iridium-192 source contribute significantly to the dose at short distances from the source (12).

B. Plastic water phantom

    To comply with TG-43 brachytherapy dosimetry protocol, measurements had to be performed in water or in a tissue-equivalent phantom (13). To best simulate the surroundings in which the sourcewire will ultimately be used, measurements were made in the Plastic Water™ phantom material manufactured by Nuclear Associates (14) (density 1.03 g/cm3) which can be substituted for muscle and other body tissues. The phantom material is solid and easily machined to accommodate a wide range of dosimetric applications. The catheter and GafChromic™ film are placed in the middle of two blocks each having dimensions of 7 cm x 30 cm x 30 cm. To allow the film and sourcewire to lay flat (see Fig. 2), a groove for the catheter and the GafChromic™ film were machined-cut into the phantom blocks.

C. Radiochromic film and calibration technique

   Radiochromic film is a clear transparent film before irradiation and upon irradiation turns different shades of blue depending on the dose delivered to the film. No physical, chemical, or thermal processing is required to bring out this color and relatively little change in color density occurs following the initial 24 hours after exposure (15). Radiochromic film has a very high spatial resolution (1200 lines per mm). The high spatial resolution and low sensitivity of radiochromic films make the dosimeter ideal for measuring dose distributions in regions of high dose gradient in radiation fields (16). The uniformity, linearity and reproducibility are also important characteristics of this film. The radiochromic film (see Fig. 3) used in this study is optimal for dose measurements in the range of 3-100 Gy. The total thickness of the film is 278 mm and composed of two sensitive layers that are each 15 mm thick.
   All radiochromic film must be calibrated to determine the dose as a function of the degree of bluing of the film due to the exposure from specific radiation sources(17). Calibration required a 320 KV x-ray tube filtered with aluminum plates to harden the beam producing an effective photon energy of 110 keV. An ion chamber monitored the dose rate during the exposure in (R/min). The film was set aside for a period of sevendays to allow for the color change to stabilize. After 7 days, the film was scanned with a Nikon LS 1000 (18) slide scanner and analyzed with National Institute of Health (NIH) Image Software (19). The pixel intensity (gray level) of the exposed film was acquired with the software. The dose to the film was determined as a function of the degree of bluing (graying). A calibration transfer function was established for later use with the sourcewire exposures. The film was scanned at 7 and 30 days to verify the post-irradiation color stability with time that is associated with radiochromic film.

D. Dose determination

    To verify the agreement between MCNP4B simulated dose calculations and empirical data the physical configurations were similarly modeled. The catheter was set in the Plastic Water™ phantom. Using the AngioRad™ afterloader system, the sourcewire was fed through the catheter. The sourcewire stopped directly under the radiochromic film and exposed the film for a prescribed amount of time. The exposed film (see FIG. 4) was then removed and placed in storage for a period of seven days. This same storage period was used for the film calibration. As per AAPM Task Group 55, the film was stored at a constant temperature and away from all sources of light. In order to establish confidence in Gafchromic film dosimetry, several measurements of varying exposure times were performed in the tissue-equivalent phantom on both the standard catheter as well as the platinum coated catheter.
    As with the calibration film, the source film was similarly scanned and analyzed to determine the dose (Gy) at a point P, at a distance sd on the source film (see FIG. 5). We utilized our calibration-transfer function to determine the dose distribution of our exposed Iridium-192sourcewire film. As with the calibration exposures, the sourcewire exposures were scanned at an interval of 7 days and 30 days to verify the post-irradiation color stability with time that is a associated with radiochromic film.

E. Monte Carlo simulation code

   Monte Carlo simulation is a technique that generates solutions to mathematical problems by performing statistical sampling. The Monte Carlo simulation code MCNP4B was utilized in our experiment to derive dosimetric data around the sourcewire. MCNP4B is a general purpose Monte Carlo code for determining the transport of neutrons, photons and/or beta particles in various geometries. This MCNP4B code is well established and experimentally verified here and elsewhere. MCNP4B software requires information known about the materials, geometry, radionuclides and their energy schemes to determine particle fluence and dose determination within the geometry. An analytical tracking is performed for every primary particle initiated in a random position and emitted in a random direction within the active source. The Iridium-192 source and its surrounding geometry were simulated using the code, and the dose distribution was acquired for a series of radial distances from the center of the source. MCNP4B was used to calculate the dose contribution from both electrons and photons separately. Electron simulations include atomic electrons and the continuous beta spectrum. Using this information, the particle fluence

at each spatial coordinate r, direction of flight path W, and Energy E is generated. Using this quantity, dose at position can be calculated for either electrons or photons as shown:

where men/r is the mass energy absorption coefficient and dT/rdx is the collision mass stopping power. In determining the total dose due to both the photons and electrons, 20 and 4 million source particles were utilized, respectively. The large number of histories resulted in a final dose determination within an acceptable relative uncertainty less than 5%.


III. RESULTS AND DISCUSSION


A. Comparison of the standard and platinum coated catheter MCNP4B computer simulation
data

   Using the MCNP4B code, the dose rate (cGy/sec•Ci) was calculated as a function of radial distance (mm) from the center of the sourcewire. For the standard catheter (see FIG. 6a and Table I, columns 1 and 2), the electron contribution exhibits a steep dose rate gradient near the sourcewire and falls to near zero at 1.6 mm. As the electrons are attenuating in the medium, the photons begin to contribute significantly to the dose rate at about 1.1 mm and continue to be the major contributor to the dose rate thereafter. Near the sourcewire, the total dose rate is extremely high (85 cGy/sec•Ci), due mostly to electrons. This is a very significant dose rate to the tissue (Endothelium and Intima) near the sourcewire in small diameter arteries as compared to the inner vessel wall. The total dose rate gradient at 1.0 mm (20 cGy/sec•Ci) to 2.0 mm (5 cGy/sec•Ci) is still quite steep. The total dose rate gradient at 2.0 mm (4 cGy/sec•Ci) to 5.0 mm (1.5 cGy/sec•Ci) levels off considerably.
  For the platinum coated catheter sourcewire, (see FIG. 6b and Table I, columns 1 and 4), the dose rate for the electron contribution calculated in the MCNP4B simulation is severely inhibited. The electron contribution to the total dose rate falls off significantly between 0.5 mm and 0.8 mm. Photons are the major contributor of the dose rate from the sourcewire to the 5.0 mm limit. Near the sourcewire, the total dose rate is 23 cGy/sec•Ci. The total dose rate for the platinum catheter is approximately one-third of the dose rate of the standard catheter out to 1.0 mm.
The total dose rate gradient at 1.0 mm (8.0 cGy/sec•Ci) to 2.0 mm (4 cGy/sec•Ci) levels off more smoothly than the standard catheter in this range. The total dose rate gradient at 2.0 mm (4 cGy/sec•Ci) and 5.0 mm (1.5 cGy/sec•Ci) is similar to the standard catheter total dose rate. The relative error associated with the MCNP4B simulation data is generated individually for each tally by the code and corresponds to one standard deviation of the mean. The absolute error corresponding to 2 standard deviations, is less than 2% for photon simulation and less than 5% for electron simulations.

B. Comparison of MCNP4B computer simulation data to the film studies data

 Using the MD-55-2 GafChromic film™, measurements were made of the dose rate as a function of radial distance (mm) from the center of the sourcewire. For the standard catheter sourcewire film study, (see FIG. 6c and Table 1, columns 1 and 3), the total dose rate exhibits a steep dose rate gradient near the sourcewire. There is a pronounced difference or under response of the dose rate data between the film study and the computer simulation. Beyond 1.0 mm, as the electrons are attenuated in the medium, the film study dose rate matches the computer simulation dose rate. For the platinum coated catheter sourcewire film study, (see FIG. 6d and Table I, columns 1 and 5), the MD-55-2 film study dose rate matches the MCNP4B computer simulation data very closely.


IV. CONCLUSION

  The platinum coated catheter effectively shields the electron contribution to the dose rate. The platinum filter provides the irradiated vessel wall with a more linear dose rate. Utilizing the standard catheter, the dose to the vessel wall will not be linear with respect to distance from the source wire. This data does not imply a more effective means for treatment, which is beyond the scope of this paper. MCNP4B code can accurately predict the dosimetric parameters around a high dose rate Iridium-192 sourcewire. MCNP4B computer simulations and experimental techniques were used to completely characterize the dose rate distribution around the newly designed AngioRad™ high intensity Iridium-192 sourcewire. The GafChromic film study performed in this paper verified the MCNP4B computer simulation data.
  Originally, the platinum was introduced to verify the accuracy of the MCNP4B computer simulation data since we suspected that the film was under responding to a field containing a large distribution of low-energy electrons. Atomic electrons and beta particles originating in the Iridium-192 source core contribute significantly to the dose rate at short distances from the source. It is shown that the lower than expected dose rates per curie measured by the film with the standard catheter could be explained if the film under responds to photon energies below 100 keV. There are other studies that point to this under-response of radiochromic film to photon energies below 100 keV (20).

Acknowledgments

 The authors wish to thank AngioRad™ System for providing the HDR afterloader system and the Iridium-192 sourcewire used in our study.

a)Author to whom correspondence should be addressed; e-mail:ppapin@sciences.sdsu.edu

        This paper is under review for publication in Medical Physics

S. Pai, L. E. Reinstein, G. Gluckman, Z. Xu, and T. Weiss, “The use of improved radiochromic film for in vivo quality assurance of high dose rate brachytherapy,” Med Phys. 25, 1217-1221 (1999).

The Afterloader and Iridium-192 sourcewire were provided by Interventional Therapies LLC, United States Surgical Corporation, Norwalk, Ct., USA.

A. Durairaj and D. P. Faxon, “The ARTISTIC and ARREST trials.” J Invasive Cardiol. 12(1), 44-9 (2000).

D. Schaart, M. C. Clarijs, and A. J. J. Bos, “On the applicability of the AAPM TG-60/TG-43 dose calculation formalism to intravascular line sources: Proposal for an adapted formalism,” Med Phys. 28, 638-654 (2001).

R. Nath, L. Anderson, G. Luxton, K. Weaver, J. F. Williamson, and A. S. Meigooni, “Dosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy Committee Task Group 43,” Med. Phys. 22, 209-234 (1995).

GafChromic Dosimetry Media Data Sheet, Nuclear Associates, 100 Voice Road, Carle Place, NY 11514-0349. Also available at http://www.victoreen.com

J. F. Briemeister, “MCNP-A general Monte Carlo n-particle transport code, version 4B,”. Los Alamos National Laboratory Report No. LA-13181, 1997.

R. Nath et al., “Intravascular brachytherapy physics: Report of the AAPM Radiation Therapy Committee Task Group 60,” Med. Phys. 26, 119-152 (1999).

Figure 2

MD-55-2 Gafchromic Film™ is composed of a highly uniform transparent coating, sensitive to ionizing radiation. The two thin radiosensitive layers are made of colorless organic microcrystals of a radiation-sensitive monomer uniformly dispersed in a gelatin binder on a polyester base.

Plastic Water

Radiochromic Film

Iridium-192 Source

"Intravascular Brachytherapy: An Opportunity for Radiation Oncology?"
Charles W. Coffey II, PhD

Percutaneous transluminal coronary angioplasty is an interventional procedure to open obstructed (stenotic) coronary arteries. However, restenosis is a significant problem associated with these balloon angioplasty procedures. Over the years, both physical and chemical methods have been tried, with limited success, to reduce the incidence of restenosis following balloon angioplasty.

Beginning in 1995, phase I clinical trials were begun in the United States to investigate the safety and efficacy of using radiation to reduce this restenotic process. Since that time, a number of trials have been initiated not only to study the issues of safety and efficacy but also to investigate a variety of methods for intravascular brachytherapy radiation dose delivery.

Coronary Intravascular Brachytherapy: Gamma or Beta
P. Tripuraneni
Radiation Oncology, Scripps Clinic, La Jolla, CA, USA

Over the past five years, more than five thousand patients have been enrolled onto coronary vascular brachytherapy protocols. The data for decreasing restenosis with application of brachytherapy in patients with in-stent restenosis is maturing, and both gamma and beta radiation delivery systems are close to formal FDA approval. The first landmark trial was SCRIPPS I, a 55 patient, single-center randomized study using 192Ir based system demonstrated a statistically significant 68% decrease in target lesion revascularization (TLR) and 48% decrease in angiographic restenosis at 3 year follow-up. A second, single-center, 130 patient, 192Ir based system randomized trial, WRIST, confirmed a statistically significant reduction in clinical and angiographic restenosis.

The next landmark trial, GAMMA I, is first multi centered randomized trial using 192Ir based system involved 12 institutions and 252 patients. This trial showed a statistically significant 47% reduction in TLR and 56% reduction of in-stent restenosis. A follow-up GAMMA II multi-centered registry of 125 patients using simplified dosimetry showed similar improved outcome compared to the placebo arm of GAMMA I. The efficacy of 90Sr/Y based system was confirmed by the multi-centered, 476 patient randomized START trial and showed a statistically significant reduction in TLR of 44% and a 66% decrease in angiographic restenosis at 8 month follow-up. The pending results of the START 40/20 multicentered registry are eagerly anticipated. The results of INHIBIT trail using P-32 based system are also eagerly awaited.
It is not possible, however, to compare the gamma and beta trials directly due to different entry criteria. For example, the lesion length in the START trial was restricted to a maximum of 20 mm, whereas the GAMMA I and II trials included lesions up to 45mm. The TLR arte of 45% in the placebo arm of GAMMAI and TLR rate of 23% in the placebo arm of START confirm that the risk actors of the patients enrolled into these trials are very different and thereby direct comparison is not possible at this time.

For de-novo stenotic lesions, the results of the BETAMED dose-finding study using 90Y based system are promising and indicate a decrease in restenosis at higher dose levels. The pending results of another land mark trial, BETA CATH, with 1456 patient, multicentered, randomized 90Sr/Y based system trial for de-novo stenotic lesions have the potential to change the field of interventional cardiology dramatically if significantly positive.
With better understanding and application of radiation oncology concepts to vascular brachytherapy, problems such as geographic miss and/or edge restenosis should be overcome. The complication of subacute thrombosis should also become less significant by eliminating restenting at the brachytherapy procedure and the prolonged use of anti-platelet therapy. While there are other competing modalities such as Rapamycin and Taxol coated stents, sonotherapy etc in the very early phases of clinical trials, the future of intravascular brachytherapy appears bright.

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Physics Today Article
Physicists and physicians are working together to devise new methods for exploiting the power of ionizing radiation to treat cancer and coronary artery disease.

Bert M. Coursey and Ravinder Nath

Each year in the US, about 200 000 patients receive therapy with radionuclides, most commonly in the form of sealed sources for treating gynecological and head and neck cancers and radiopharmaceuticals for treating thyroid cancer. Known as brachytherapy, this kind of treatment has attracted a resurgence of interest in the medical world, primarily because it offers a simple procedure for delivering high radiation doses to a tumor but minimal doses to the surrounding healthy tissue. Brachytherapy can provide this optimal dose distribution because radiation sources are implanted either in the tumor or very close to it. (Brachys is Greek for “near.”) This advantage is not shared by external beam therapy, in which the source of radiation is about 1 m away from the patien

Recent successes with two new forms of radionuclide therapy—radioactive seeds for treating prostate cancer and radioactive sources for preventing the reclosing of arteries following balloon angioplasty—presage the treatment of hundreds of thousands of additional patients annually in the US alone. And radiopharmaceuticals containing many of the same radionuclides also offer promise for treating certain cancers that have been resistant to other types of therapy.

A brief history
Radionuclides were first used in therapy nearly a century ago, after Pierre Curie and others noticed that radium sources brought into prolonged contact with skin produced burns. Physicians used this observation to design treatments for surface lesions, such as those seen in lupus. By 1915, therapy with sealed sources of radium-226 or radon-222 had become widely available. But in the 1940s and 1950s, as concerns grew about the risks of radiation exposure to medical personnel, medical professionals lost interest in brachytherapy.

Two technical innovations began to allay those concerns. In the 1950s, so-called afterloading techniques (remote source handling with increasingly sophisticated robotics) were introduced that dramatically reduced personnel exposure. Around the same time, several new reactor-produced radionuclides with better radiation safety characteristics became available. For example, when ready supplies of cobalt-60 (which has a high specific activity, a 5.27-y halflife, and 1.25-MeV gamma rays) became available 40 years ago, external beam therapy with 60Co quickly supplanted the 250-kV x-ray tubes then in use. Even today, 60Co machines remain a vital and dominant treatment option for radiotherapy in developing countries. During the same period, the fission product cesium-137 became available as a safer alternative to 226Ra for brachytherapy, and it is still in active use for treating gynecological cancers. (See box 1 below for information on how radioactivity is quantified.)
Radionuclide therapy remains an important treatment option today because ionizing radiation from radionuclides can kill cells, and thus inhibit growth in the benign and cancerous lesions that result from proliferative diseases. Other cytotoxic agents exist, but radiation is simply the most effective way of controlling the proliferation of cells without unacceptable morbidity. It is the treatment of choice for a large number of cancer patients. Radiation kills cells by damaging the DNA in the cell nucleus, thereby inhibiting cellular reproduction. To damage DNA, the energy of the radiation—in the form of photons, electrons, or heavier charged particles—has to exceed a few tens of electron volts. However, if the radiation is delivered from outside the body, as in external beam radiotherapy, then photon energies of several million electron volts are needed simply to penetrate the tissues and reach the deeper-seated tumors in the body. By contrast, brachytherapy implants can be successfully performed with radionuclides that emit photons with energies as low as 20 keV. For example, palladium-103, which is used for prostate implantation, has an average energy of just 21 keV. Radiopharmaceutical therapies also allow a radionuclide to deliver its decay energy close to, or even inside, the target cells.