Monte Carlo model for a prototype CT-compatible, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer.

PURPOSE: Current, clinically applicable intracavitary brachytherapy applicators that utilize shielded ovoids contain a pair of tungsten-alloy shields which serve to reduce dose delivered to the rectum and bladder during source afterloading. After applicator insertion, these fixed shields are not necessarily positioned to provide optimal shielding of these critical structures due to variations in patient anatomies. The authors present a dosimetric evaluation of a novel prototype intracavitary brachytherapy ovoid [anatomically adaptive applicator (A3)], featuring a single shield whose position can be adjusted with two degrees of freedom: Rotation about and translation along the long axis of the ovoid. METHODS: The dosimetry of the device for a HDR 192Ir was characterized using radiochromic film measurements for various shield orientations. A MCNPX Monte Carlo model was developed of the prototype ovoid and integrated with a previously validated model of a v2 mHDR 192Ir source (Nucletron Co.). The model was validated for three distinct shield orientations using film measurements. RESULTS: For the most complex case, 91% of the absolute simulated and measured dose points agreed within 2% or 2 mm and 96% agreed within 10% or 2 mm. CONCLUSIONS: Validation of the Monte Carlo model facilitates future investigations into any dosimetric advantages the use of the A3 may have over the current state of art with respect to optimization and customization of dose delivery as a function of patient anatomical geometries.

Comparison of a 3-D multi-group SN particle transport code with Monte Carlo for intracavitary brachytherapy of the cervix uteri.

A patient dose distribution was calculated by a 3D multi-group S N particle transport code for intracavitary brachytherapy of the cervix uteri and compared to previously published Monte Carlo results. A Cs-137 LDR intracavitary brachytherapy CT data set was chosen from our clinical database. MCNPX version 2.5.c, was used to calculate the dose distribution. A 3D multi-group S N particle transport code, Attila version 6.1.1 was used to simulate the same patient. Each patient applicator was built in SolidWorks, a mechanical design package, and then assembled with a coordinate transformation and rotation for the patient. The SolidWorks exported applicator geometry was imported into Attila for calculation. Dose matrices were overlaid on the patient CT data set. Dose volume histograms and point doses were compared. The MCNPX calculation required 14.8 hours, whereas the Attila calculation required 22.2 minutes on a 1.8 GHz AMD Opteron CPU. Agreement between Attila and MCNPX dose calculations at the ICRU 38 points was within +/- 3%. Calculated doses to the 2 cc and 5 cc volumes of highest dose differed by not more than +/- 1.1% between the two codes. Dose and DVH overlays agreed well qualitatively. Attila can calculate dose accurately and efficiently for this Cs-137 CT-based patient geometry. Our data showed that a three-group cross-section set is adequate for Cs-137 computations. Future work is aimed at implementing an optimized version of Attila for radiotherapy calculations.

Feasibility of a multigroup deterministic solution method for three-dimensional radiotherapy dose calculations.

PURPOSE: To investigate the potential of a novel deterministic solver, Attila, for external photon beam radiotherapy dose calculations. METHODS AND MATERIALS: Two hypothetical cases for prostate and head-and-neck cancer photon beam treatment plans were calculated using Attila and EGSnrc Monte Carlo simulations. Open beams were modeled as isotropic photon point sources collimated to specified field sizes. The sources had a realistic energy spectrum calculated by Monte Carlo for a Varian Clinac 2100 operated in a 6-MV photon mode. The Attila computational grids consisted of 106,000 elements, or 424,000 spatial degrees of freedom, for the prostate case, and 123,000 tetrahedral elements, or 492,000 spatial degrees of freedom, for the head-and-neck cases. RESULTS: For both cases, results demonstrate excellent agreement between Attila and EGSnrc in all areas, including the build-up regions, near heterogeneities, and at the beam penumbra. Dose agreement for 99% of the voxels was within the 3% (relative point-wise difference) or 3-mm distance-to-agreement criterion. Localized differences between the Attila and EGSnrc results were observed at bone and soft-tissue interfaces and are attributable to the effect of voxel material homogenization in calculating dose-to-medium in EGSnrc. For both cases, Attila calculation times were <20 central processing unit minutes on a single 2.2-GHz AMD Opteron processor. CONCLUSIONS: The methods in Attila have the potential to be the basis for an efficient dose engine for patient-specific treatment planning, providing accuracy similar to that obtained by Monte Carlo.

Optimization of deterministic transport parameters for the calculation of the dose distribution around a high dose-rate 192Ir brachytherapy source.

The goal of this work was to calculate the dose distribution around a high dose-rate 192Ir brachytherapy source using a multi-group discrete ordinates code and then to compare the results with a Monte Carlo calculated dose distribution. The unstructured tetrahedral mesh discrete ordinates code Attila version 6.1.1 was used to calculate the photon kerma rate distribution in water around the Nucletron microSelectron mHDRv2 source. MCNPX 2.5.c was used to compute the Monte Carlo water photon kerma rate distribution. Two hundred million histories were simulated, resulting in standard errors of the mean of less than 3% overall. The number of energy groups, S(n) (angular order), P(n) (scattering order), and mesh elements were varied in addition to the method of analytic ray tracing to assess their effects on the deterministic solution. Water photon kerma rate matrices were exported from both codes into an in-house data analysis software. This software quantified the percent dose difference distribution, the number of points within +/- 3% and +/- 5%, and the mean percent difference between the two codes. The data demonstrated that a 5 energy-group cross-section set calculated results to within 0.5% of a 15 group cross-section set. S12 was sufficient to resolve the solution in angle. P2 expansion of the scattering cross-section was necessary to compute accurate distributions. A computational mesh with 55 064 tetrahedral elements in a 30 cm diameter phantom resolved the solution spatially. An efficiency factor of 110 with the above parameters was realized in comparison to MC methods. The Attila code provided an accurate and efficient solution of the Boltzmann transport equation for the mHDRv2 source.

N-ethyl-N-nitrosourea (ENU)-induced meningiomatosis and meningioma in p16(INK4a)/p19(ARF) tumor suppressor gene-deficient mice.

The cyclin-dependent kinase (CDK) inhibitor p16(INK4a) and the MDM2 ubiquitin ligase inhibitor p19(ARF) are critical to the regulation of cell cycle progression. Their loss by deletion, mutation or epigenetic silencing is a common molecular alteration in many human cancers. To investigate the role of p16(INK4a)/p19(ARF) deficiency in CNS tumor pathogenesis, pregnant mice bearing p16(-/-)/p19(-/-), p16(+/-)/p19(+/-), and p16(+/+)/p19(+/+) embryos were exposed transplacentally on gestation day 14 to a single dose of the potent carcinogen, ethylnitrosourea (ENU). p16(+/-)/p19(+/-) male mice treated with ENU developed meningial proliferative lesions with a high incidence (5/10). The incidence was lower in other ENU-treated animals of both sexes and none occurred in saline-treated control animals. The lesions ranged from widespread meningeal proliferation and plaque-like thickening by neoplastic spindle cells consistent with meningiomatosis to a larger discrete mass consistent with a meningioma. Ultrastructural analysis revealed the presence of intercellular junctions between cells, supporting a meningothelial histogenesis. Spontaneous meningiomas occur rarely in wild-type mice but are a common neoplasm afflicting humans, accounting for between 13 and 26% of primary intracranial neoplasms. This ENU inducible meningeal lesion in p16(+/-)/p19(+/-) mice may provide additional insight into the pathogenesis of meningeal neoplasia and aid the development of therapeutics.

Retrospective dosimetric comparison of low-dose-rate and pulsed-dose-rate intracavitary brachytherapy using a tandem and mini-ovoids.

The purpose of this study was to compare the dose distribution of Iridium-192 ((192)Ir) pulsed-dose-rate (PDR) brachytherapy to that of Cesium-137 ((137)Cs) low-dose-rate (LDR) brachytherapy around mini-ovoids and an intrauterine tandem. Ten patient treatment plans were selected from our clinical database, all of which used mini-ovoids and an intrauterine tandem. A commercial treatment planning system using AAPM TG43 formalism was used to calculate the dose in water for both the (137)Cs and (192)Ir sources. For equivalent system loadings, we compared the dose distributions in relevant clinical planes, points A and B, and to the ICRU bladder and rectal reference points. The mean PDR doses to points A and B were 3% +/- 1% and 6% +/- 1% higher than the LDR doses, respectively. For the rectum point, the PDR dose was 4% +/- 3% lower than the LDR dose, mainly because of the (192)Ir PDR source anisotropy. For the bladder point, the PDR dose was 1% +/- 4% higher than the LDR dose. We conclude that the PDR and LDR dose distributions are equivalent for intracavitary brachytherapy with a tandem and mini-ovoids. These findings will aid in the transfer from the current practice of LDR intracavitary brachytherapy to PDR for the treatment of gynecologic cancers.

Comparison between an event-by-event Monte Carlo code, NOREC, and ETRAN for electron scaled point kernels between 20 keV and 1 MeV.

An event-by-event Monte Carlo code called NOREC, a substantially improved version of the Oak Ridge electron transport code (OREC), was released in 2003, after a number of modifications to OREC. In spite of some earlier work, the characteristics of the code have not been clearly shown so far, especially for a wide range of electron energies. Therefore, NOREC was used in this study to generate one of the popular dosimetric quantities, the scaled point kernel, for a number of electron energies between 0.02 and 1.0 MeV. Calculated kernels were compared with the most well-known published kernels based on a condensed history Monte Carlo code, ETRAN, to show not only general agreement between the codes for the electron energy range considered but also possible differences between an event-by-event code and a condensed history code. There was general agreement between the kernels within about 5% up to 0.7 r/r (0) for 100 keV and 1 MeV electrons. Note that r/r (0) denotes the scaled distance, where r is the radial distance from the source to the dose point and r (0) is the continuous slowing down approximation (CSDA) range of a mono-energetic electron. For the same range of scaled distances, the discrepancies for 20 and 500 keV electrons were up to 6 and 12%, respectively. Especially, there was more pronounced disagreement for 500 keV electrons than for 20 keV electrons. The degree of disagreement for 500 keV electrons decreased when NOREC results were compared with published EGS4/PRESTA results, producing similar agreement to other electron energies.

Comparison of a finite-element multigroup discrete-ordinates code with Monte Carlo for radiotherapy calculations.

Radiotherapy calculations often involve complex geometries such as interfaces between materials of vastly differing atomic number, such as lung, bone and/or air interfaces. Monte Carlo methods have been used to calculate accurately the perturbation effects of the interfaces. However, these methods can be computationally expensive for routine clinical calculations. An alternative approach is to solve the Boltzmann equation deterministically. We present one such deterministic code, Attila. Further, we computed a brachytherapy example and an external beam benchmark to compare the results with data previously calculated by MCNPX and EGS4. Our data suggest that the presented deterministic code is as accurate as EGS4 and MCNPX for the transport geometries examined in this study.

Dose modification factors for 192Ir high-dose-rate irradiation using Monte Carlo simulation.

A recently introduced brachytherapy system for partial breast irradiation, MammoSite, consists of a balloon applicator filled with contrast solution and a catheter for insertion of an 192Ir high-dose-rate (HDR) source. In using this system, the treatment dose is typically prescribed to be delivered 1 cm from the balloon's surface. Most treatment-planning systems currently in use for brachytherapy procedures use water-based dosimetry with no correction for heterogeneity. Therefore, these systems assume that full scatter exists regardless of the amount of tissue beyond the prescription line. This assumption might not be a reasonable one, especially when the tissue beyond the prescription line is thin. In such a case, the resulting limited scatter could cause an underdose to be delivered along the prescription line. We used Monte Carlo simulations to investigate how the thickness of the tissue between the surface of the balloon and the skin or lung affected the treatment dose delivery. Calculations were based on a spherical water phantom with a diameter of 30 cm and balloons with diameters of 4 cm, 5 cm, and 6 cm. The dose modification factor is defined as the ratio of the dose rate at the typical prescription distance of 1 cm from the balloon's surface with full scatter obtained using the water phantom to the dose rate with a finite tissue thickness (from 0 cm to 10 cm) beyond the prescription line. The dose modification factor was found to be dependent on the balloon diameter and was 1.098 for the 4-cm balloon and 1.132 for the 6-cm balloon with no tissue beyond the prescription distance at the breast-skin interface. The dose modification factor at the breast-lung interface was 1.067 for the 4-cm balloon and 1.096 for the 6-cm balloon. Even 5 cm of tissue beyond the prescription distance could not result in full scatter. Thus, we found that considering the effect of diminished scatter is important to accurate dosimetry. Not accounting for the dose modification factor may result in delivering a lower dose than is prescribed.

The optimization of dose delivery for intraoperative high-dose-rate radiation therapy using curved HAM applicators.

BACKGROUND AND PURPOSE: To determine the effect of the curvature of Harrison-Anderson-Mick applicators on the dose distribution in high-dose-rate intraoperative radiation therapy (HDR-IORT). MATERIAL AND METHODS: Treatment planning was performed with flat applicators using (192)Ir as the radioactive source, and dwell times were optimized using dose-point optimization techniques. These optimized dwell times were then used for the curved applicators, and the dose distributions that would actually be delivered to patients were determined. RESULTS: The dose directly below the central catheter was strongly dependent on the curvature of the applicator. Steep parabolic curves caused underdoses of as much as 19% at a point 1cm from the convex side of the applicator. The rate of dose reduction with increasing distance from the applicator surface was also a function of the curvature of the applicator. CONCLUSIONS: The curvature of the applicator profoundly affects dosimetry and can be exploited to optimize coverage of the target during HDR-IORT procedures. To ensure accurate dose delivery, these dose perturbations must be accounted for in the planning process. We recommend maintaining a dosimetry atlas of various applicator sizes and curvatures in addition to one for flat applicators.

Monte Carlo calculations of the dose distribution around a commercial gynecologic tandem applicator.

BACKGROUND AND PURPOSE: Dose rate distributions around Fletcher Suit Delclos (FSD) tandem applicators used for intracavitary brachytherapy are usually calculated by assuming each source is a point source and summing the contributions from each of the sources. Consequently, interpellet attenuation and scattering are ignored. Additional error may be introduced because the applicator walls and tip screw are not considered. The focus of this study was a Monte Carlo simulation of a Selectron tandem, verification of the calculations, and presentation of the implications of the point-source approximation for treatment planning. MATERIALS AND METHODS: MCNPX 2.4.k was used to calculate dose rate distributions around straight and curved tandems. The Monte Carlo calculations were verified with radiochromic film. RESULTS: MCNPX calculated dose to within +/-2% or +/-2 mm for 97% of the points on the film parallel to the long axis and 98% on a film perpendicular to the long axis of the straight portion of the tandem. The point source approximation overestimated dose by as much as 33% superior to the tip of the tandem as compared to MCNPX. The point source approximation overestimated dose when photons passed through multiple pellets by as much as 18% as compared to MCNPX. Laterally, the dose distribution was not affected greatly. CONCLUSIONS: Interpellet attenuation was a dominant factor in determining the distribution along the length of the pellet train. MCNPX calculated doses accurately when the pellets and applicator walls were included in the geometry. The point source approximation is adequate lateral to the tandem. The point source approximation does not calculate dose accurately superior to the tandem or when photons pass through multiple pellets.

Dosimetric evaluation of the Fletcher-Williamson ovoid for pulsed-dose-rate brachytherapy: a Monte Carlo study.

We used radiochromic film dosimetry to validate a Monte Carlo (MC) model of a 192Ir pulsed-dose-rate (PDR) source inside a Fletcher-Williamson ovoid. MD-55-2 radiochromic film was placed in a high-impact polystyrene phantom in a plane parallel to and displaced 2.0 cm medially from the long axis of the ovoid. MC N-particle transport code (MCNPX) version 2.4 was used to model the ovoid and the 192Ir source. Energy deposition was calculated using a track-length estimator modified by an energy-dependent heating function, which is a good approximation of the collision kerma. To convert the estimates of the MC dose per simulated particle to clinically relevant absolute dosimetry, additional MC models of an actual and a virtual 192Ir source in dry air were simulated to determine air kerma strength for the penetrating part of the photon spectrum (>11.3 keV). The absolute dose distributions predicted by MCNPX agreed with the film results and were within +/-9.4% (k = 2) and within +/-2% or within a distance to agreement of 2 mm for 94% of the dose grid. Additional MC models characterized the uncertainty resulting from source positioning inside the ovoid. For a worst-case scenario of 1 mm off centre from the nominal source position in the 3 mm diameter ovoid shaft, the average dose deviation over the film plane was +/-5% (1sigma = +/-4%), with maximum deviation near the sharp dose-gradient provided by the shields of -20% to + 26%. A validated MC model is the first requirement to simulate common LDR clinical loadings (5-20 mgRaEq) and, thus, will aid in the transition from the current 137Cs Selectron LDR ICBT to PDR for treatment of gynecologic cancers.

A three-dimensional computed tomography-assisted Monte Carlo evaluation of ovoid shielding on the dose to the bladder and rectum in intracavitary radiotherapy for cervical cancer.

PURPOSE: To determine the effects of Fletcher Suit Delclos ovoid shielding on dose to the bladder and rectum during intracavitary radiotherapy for cervical cancer. METHODS AND MATERIALS: The Monte Carlo method was used to calculate the dose in 12 patients receiving low-dose-rate intracavitary radiotherapy with both shielded and unshielded ovoids. Cumulative dose-difference surface histograms were computed for the bladder and rectum. Doses to the 2-cm(3) and 5-cm(3) volumes of highest dose were computed for the bladder and rectum with and without shielding. RESULTS: Shielding affected dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the rectum (10.1% and 11.1% differences, respectively). Shielding did not have a major impact on the dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the bladder. The average dose reduction to 5% of the surface area of the bladder was 53 cGy. Reductions as large as 150 cGy were observed to 5% of the surface area of the bladder. The average dose reduction to 5% of the surface area of the rectum was 195 cGy. Reductions as large as 405 cGy were observed to 5% of the surface area of the rectum. CONCLUSIONS: Our data suggest that the ovoid shields can greatly reduce the radiation dose delivered to the rectum. We did not find the same degree of effect on the dose to the bladder. To calculate the dose accurately, however, the ovoid shields must be included in the dose model.

Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with radiochromic film and normoxic polymer gel dosimetry.

The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy (ICB) for cervical cancer contain shields to reduce dose to the bladder and rectum. Many treatment planning systems (TPS) do not include the shields and other ovoid structures in the dose calculation. Instead, TPSs calculate dose by summing the dose contributions from the individual sources and ignoring ovoid structures such as the shields. The goal of this work was to calculate the dose distribution with Monte Carlo around a Selectron FSD ovoid and compare these calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry. Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron FSD ovoid with and without shields. RCF measurements were performed in a plane parallel to and displaced laterally 1.25 cm from the long axis of the ovoid. MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF and MAGIC gel were irradiated with four 33 microGy m2 h(-1) Cs-137 pellets for a period of 24 h. Results indicated that MCNPX calculated dose to within +/- 2% or 2 mm for 98% of points compared with RCF measurements and to within +/- 3% or 3 mm for 98% of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c can calculate dose accurately in the presence of the ovoid shields, that RCF and MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution and the ovoid shields reduce the dose by as much as 50%.

Dose perturbation of a novel cobalt chromium coronary stent on 32P intravascular brachytherapy: a monte carlo study.

Intravascular brachytherapy has been adopted for the indication of in-stent restenosis on the basis of results of clinical trials using mainly stainless steel stents. Recently, a new stent made of cobalt-chromium L-605 alloy (CoCr, p=9.22 g/cm3) (MULTI-LINK VISION) was introduced as an alternative to the 316L stainless steel stent design (SS, p=7.87 g/cm3) (MULTI-LINK PENTA). In this work, we used the Monte Carlo code MCNPX to compare the dose distribution for the 32P GALILEO source in CoCr and SS 8 mm stent models. The dose perturbation factor (DPF), defined as the ratio of the dose in water with the presence of a stent to the dose without a stent, was used to compare results. Both stent designs were virtually expanded to diameters of 2.0, 3.0, and 4.0 mm using finite element models. The complicated strut shapes of both the CoCr and SS stents were simplified using circular rings with an effective width to yield a metal-to-tissue ratio identical to that of the actual stents. The mean DPF at a 1 mm tissue depth, over the entire stented length of 8 mm, was 0.935 for the CoCr stent and 0.911 for the SS stent. The mean DPF at the intima (0.05 mm radial distance from the strut outer surface), over the entire stented length of 8 mm, was 0.950 for CoCr, and 0.926 for SS. The maximum DPFs directly behind the CoCr and SS struts were 0.689 and 0.644, respectively. All DPF estimates have a standard deviation of +/-0.6%(k=2), approximating the 95% confidence interval. Although the CoCr stent has a higher effective atomic number and greater density than the SS stent, the DPFs for the two stents are similar, probably because the metal-to-tissue ratio and strut thickness of the CoCr stent are lower than those of the SS stent.

Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with radiochromic film and normoxic polymer gel dosimetry.

The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy (ICB) for cervical cancer contain shields to reduce dose to the bladder and rectum. Many treatment planning systems (TPS) do not include the shields and other ovoid structures in the dose calculation. Instead, TPSs calculate dose by summing the dose contributions from the individual sources and ignoring ovoid structures such as the shields. The goal of this work was to calculate the dose distribution with Monte Carlo around a Selectron FSD ovoid and compare these calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry. Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron FSD ovoid with and without shields. RCF measurements were performed in a plane parallel to and displaced laterally 1.25 cm from the long axis of the ovoid. MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF and MAGIC gel were irradiated with four 33µGym2h-1 Cs-137 pellets for a period of 24 h. Results indicated that MCNPX calculated dose to within ±2% or 2 mm for 98% of points compared with RCF measurements and to within ±3% or 3 mm for 98% of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c can calculate dose accurately in the presence of the ovoid shields, that RCF and MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution and the ovoid shields reduce the dose by as much as 50%.

Contrast effects on dosimetry of a partial breast irradiation system.

MammoSite is a high-dose rate brachytherapy procedure for partial breast irradiation, which uses a balloon filled with radiopaque iodine-based contrast solution and catheter for insertion of 192Ir high-dose-rate source. The radiopaque material helps visualizing the balloon contour, catheter, and source position within the balloon, which is essential for computerized tomography-based treatment planning and for daily QA using x-ray radiographs. Because of the high content of iodine in contrast media, increased absorption and attenuation of photons may take place within the balloon, which would affect the resultant dose rates outside the balloon. The impact of the concentration of the radiopaque solution on the physical dosimetry of this brachytherapy procedure is investigated in this study using MCNPX (version 2.4) Monte Carlo simulation. Calculations were based on a 30 cm diameter water sphere phantom. The source geometry was that of the Nucletron microSelectron HDR v2 192Ir source. Concentration of the iodine-based radiopaque solution was varied from 5% to 25% by volume, a range recommended by the balloon's manufacturer. Balloon diameters of 4, 5, and 6 cm were simulated. Dose rate per unit air-kerma strength was calculated in 1 mm scoring bin steps. The dose rate reduction at the typical prescription line of 1 cm away from the balloon surface ranged from - 0.8% for the smallest balloon diameter and contrast concentration to a maximum of - 5.7% for the largest balloon diameter and contrast concentration, relative to a water-filled balloon. Limiting the contrast concentration to 10% would insure less than 3% reduction in the prescription dose, regardless of balloon diameter.

A segmented 32P source Monte Carlo model to derive AAPM TG-60 dosimetric parameters used for intravascular brachytherapy.

A new high dose rate 20 mm 32P intravascular brachytherapy (IVB) beta source used with automated stepping has recently been introduced. The AAPM Task Group 60 recommends that beta IVB sources should have well characterized dosimetric parameters in water. In this study, Monte Carlo simulations (MCNPX v 2.4) were used to derive these parameters for a 2 mm source segment rather than the entire 20 mm source to ensure the correct formulation using the traditional TG-60 and TG-43 polar coordinate system (r, theta) parameters. The dose rate at the reference depth of 2 mm, the radial dose function, and the anisotropy function were generated for the 2 mm 32P source segment at the mid-plane, distal edge and proximal edge of the original 20 mm source. Our results indicate that the anisotropy of the 2 mm distal and proximal segments are the same, but differ from that of the mid-plane segment due to the perturbation of the adjacent tungsten marker. Using the TG-60 formulation of the mid-plane and edge segments resulted in dose distributions similar to those obtained for a 20 mm linear beta source model. The segmented formulation provides a method consistent with the familiar TG-60 formulation and ability to calculate the dose-distribution inside curved vessels.

The metallothionein-null phenotype is associated with heightened sensitivity to lead toxicity and an inability to form inclusion bodies.

Susceptibility to lead toxicity in MT-null mice and cells, lacking the major forms of the metallothionein (MT) gene, was compared to wild-type (WT) mice or cells. Male MT-null and WT mice received lead in the drinking water (0 to 4000 ppm) for 10 to 20 weeks. Lead did not alter body weight in any group. Unlike WT mice, lead-treated MT-null mice showed dose-related nephromegaly. In addition, after lead exposure renal function was significantly diminished in MT-null mice in comparison to WT mice. MT-null mice accumulated less renal lead than WT mice and did not form lead inclusion bodies, which were present in the kidneys of WT mice. In gene array analysis, renal glutathione S-transferases were up-regulated after lead in MT-null mice only. In vitro studies on fibroblast cell lines derived from MT-null and WT mice showed that MT-null cells were much more sensitive to lead cytotoxicity. MT-null cells accumulated less lead and formed no inclusion bodies. The MT-null phenotype seems to preclude lead-induced inclusion body formation and increases lead toxicity at the organ and cellular level despite reducing lead accumulation. This study reveals important roles for MT in chronic lead toxicity, lead accumulation, and inclusion body formation.