Monte Carlo-aided dosimetry of a new high dose-rate brachytherapy source

In this article we introduce a new high-intensity 192Ir source design for use in a recently reengineered microSelectron-HDR remote afterloading device for high dose-rate (HDR) brachytherapy. The maximum rigid length and outer diameter of the new source are reduced to 4.95 and 0.90 mm, respectively, compared to 5.50 and 1.10 mm for the previous source design introduced in 1991. In addition, a smaller diameter and more flexible steel cable are used, allowing the source cable to negotiate smaller diameter catheters or more tortuously curved catheters. Using Monte Carlo photon transport simulation, the complete two-dimensional (2-D) dose-rate distribution is calculated over the 0.1-7 cm distance range and are presented both as conventional 2-D Cartesian lookup tables and in the formalism recommended by the American Association of Physicists in Medicine Task Group 43 (TG-43) Report. The dose distribution of this source is very similar to that of its predecessor, except near the source tip and in the shadow of the cable assembly, where differences of 5%-8% are apparent. The accuracy of various methods for extrapolating beyond the tubulated anisotropy functions to short distances is evaluated. It is demonstrated that linear extrapolation from the anisotropy functions defined by TG-43 accurately (+/- 2%) estimates dose rate at short and long distances lying outside the radial distance range of the original measured data from which the anisotropy and radial dose functions were derived. In contrast, the algorithm used on the vendor's planning system results in large calculation errors at distances less than 5 mm.     

In vitro reconstitution of neurotransmitter release

Photon activation is a radiotherapy technique in which an element is added to the absorbing medium to raise the probability that a photoelectric interaction will occur, thus causing an increase in the absorption of ionizing radiation. Binding energies of key elements within an absorbing medium are closely matched with the incident photon energies to maximize the production of free electrons and subsequent absorption of their kinetic energies. The purpose of this research was to quantify potential dose enhancement using a silver tetraphenyl sulfonato porphyrin (AgTPPS4) in tumors as a photon activator for use with interstitial 125I brachytherapy. A three-dimensional Monte Carlo dosimetry model was developed using the EGS4 coding system. The photon source was modeled using spectral gamma emissions from models 6702 or 6711 brachytherapy seeds for comparison. Absorbed dose within the tumor volume was calculated for AgTPPS4 concentrations ranging between 0 and 20 mmol/kg tumor weight. These theoretical studies demonstrated linear increases in dose absorbed by the tumor with corresponding increases in AgTPPS4 concentration. The required AgTPPS4 concentration (RSC) to achieve at least a ten percent absorbed dose increase is approximately 6.5 mmol/kg tumor weight for model 6702 seeds. In vivo biodistribution and in vitro toxicity studies were conducted to determine if the theoretically derived RSC could be achieved biologically. Cell toxicity studies showed that TPPS4 porphyrin derivatives were cytotoxic at concentrations required to provide significant brachytherapy dose enhancement. Reverse phase HPLC confirmed that toxicity was due to intrinsic properties of the TPPS4 molecule, not the presence of free silver, drug impurities, or metabolites. Further research is necessary to develop a nontoxic molecular carrier for delivering silver to the DNA of tumor cells.     

Dose rate constants for 125I, 103Pd, 192Ir and 169Yb brachytherapy sources: an EGS4 Monte Carlo study

An exhaustive revision of dosimetry data for 192Ir, 125I, 103Pd and 169Yb brachytherapy sources has been performed by means of the EGS4 simulation system. The DLC-136/PHOTX cross section library, water molecular form factors, bound Compton scattering and Doppler broadening of the Compton-scattered photon energy were considered in the calculations. The absorbed dose rate per unit contained activity in a medium at 1 cm in water and air-kerma strength per unit contained activity for each seed model were calculated, allowing the dose rate constant (DRC) A to be estimated. The influence of the calibration procedure on source strength for low-energy brachytherapy seeds is discussed. Conversion factors for 125I and 103Pd seeds to obtain the dose rate in liquid water from the dose rate measured in a solid water phantom with a detector calibrated for dose to water were calculated. A theoretical estimate of the DRC for a 103Pd model 200 seed equal to 0.669 +/- 0.002 cGy h(-1) U(-1) is obtained. Comparison of obtained DRCs with measured and calculated published results shows agreement within 1.5% for 192Ir, 169Yb and 125I sources.     

Scoring functions for computational algorithms applicable to the design of spiked oligonucleotides

PURPOSE: Two developments in 125I-sealed source dosimetry have necessitated swift and accurate implementation of TG43 dosimetry in clinic: (a) the dosimetry constants of 125I endorsed by the AAPM Task Group 43 Report result in calculated dose rate that deviates by as much as 15% from currently accepted dose-rate distributions, and (b) The National Institute of Standards and Technology (NIST) has proposed modifying the 125I air-kerma strength standard by approximately 10%. METHODS AND MATERIALS: The ad hoc committee of AAPM Radiation Therapy Committee describes specific procedures to implement these two developments without causing confusion and mistakes. CONCLUSIONS: Confusion and mistakes may be avoided when the following two general steps are taken: 1) STEP I, TG-43 implementation, and 2) STEP II, new air-kerma strength standard implementation when available from NIST.     

Experimental determination of dosimetry functions of Ir-192 sources

Experimental data related to the dosimetric characteristics of Ir-192 brachytherapy sources are limited. The aim of this work was to obtain the dosimetry functions required by the American Association of Physicists in Medicine Task Group 43 for both a low and a high dose-rate iridium-192 brachytherapy source through dose measurements in a water-equivalent phantom. Dose measurements have been performed using lithium fluoride thermoluminescent detectors positioned in a polystyrene phantom at distances from the source that vary from 1 to 10 cm, with 1 cm intervals, and at angles that vary from 0 degree to 170 degrees with 10 degrees intervals. The anisotropy functions, radial dose functions, and dose rate constants were determined for both brachytherapy sources. The precision of results obtained on those relatively fine intervals of angles and distances provides clinics with the possibility to use and interpolate the complete data sets for treatment planning.     

In-water calibration of PDR 192Ir brachytherapy sources with an NE2571 ionization chamber

An ionometric calibration procedure for 192Ir PDR brachytherapy sources in terms of dose rate to water is presented. The calibration of the source is performed directly in a water phantom at short distances (1.0, 2.5 and 5.0 cm) using an NE2571 Farmer type ion chamber. To convert the measured air-kerma rate in water to dose rate to water a conversion factor (CF) was calculated by adapting the medium-energy x-ray dosimetry protocol for a point source geometry (diverging beam). The obtained CF was verified using two different methods. Firstly, the CF was calculated by Monte Carlo simulations, where the source-ionization chamber geometry was modelled accurately. In a second method, a combination of Monte Carlo simulations and measurements of the air-kerma rate in water (at 1.0, 2.5 and 5.0 cm distance) and in air (1 m distance) was used to determine the CF. The obtained CFs were also compared with conversion factors calculated with the adapted dosimetry protocol for high-energy photons introduced by T?lli. All calculations were done for a Gammamed PDR 192Ir source-NE2571 chamber geometry. The conversion factors obtained with the four different methods agree to within 1% at the three distances of interest. We obtained the following values (medium-energy x-ray protocol): CF(1 cm) = 1.458; CF(2.5 cm) = 1.162; CF(5.0 cm) = 1.112 (1 sigma = 0.7% for the three distances of interest). The obtained results were checked with TLD measurements. The values of the specific dose rate constant and the radial dose function calculated in this work are in accordance with the literature data.     

A survey of physics and dosimetry practice of permanent prostate brachytherapy in the United States

PURPOSE: To obtain data with regard to current physics and dosimetry practice in transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S. by conducting a survey of institutions performing this procedure with the greatest frequency. METHODS AND MATERIALS: Seventy brachytherapists with the greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page comprehensive questionnaire included questions on both clinical and physics and dosimetry practice. Individuals not responding initially were sent additional mailings and telephoned. Physics and dosimetry practice summary statistics are reported. Clinical practice data is reported separately. RESULTS: Thirty-five (50%) surveys were returned. Participants included 29 (83%) from the private sector and 6 (17%) from academic programs. Among responding clinicians, 125I (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most brachytherapists perform preplans (86%), predominately employing ultrasound imaging (85%). Commercial treatment planning systems are used more frequently (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are most commonly performed by a physicist (69%). A wide range of apparent activities (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg. 1.32). Of those assaying sources (71%), the range in number assayed (1 to all) and maximum accepted difference from vendor stated activity (2-20%) varies greatly. Most respondents feel that the manufacturers criteria for source activity are sufficiently stringent (88%); however, some report that vendors do not always meet their criteria (44%). Most postimplant dosimetry imaging occurs on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2 h (avg.) to complete. Calculational formalisms and parameters vary substantially. At the time of the survey, few institutions have adopted AAPM TG-43 recommendations (21%). Only half (50%) of those not using TG-43 indicated an intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi apparent activity source permanently implanted varied significantly. For 125I, doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy. CONCLUSION: While several areas of current physics and dosimetry practice are consistent among institutions, treatment planning and dose calculation techniques vary considerably. These data demonstrate a relative lack of consensus with regard to these practices. Furthermore, the wide variety of calculational techniques and benchmark data lead to calculated doses which vary by clinically significant amounts. It is apparent that the lack of standardization with regard to treatment planning and dose calculation practice in TIPPB must be addressed prior to performing any meaningful comparison of clinical results between institutions.     

How to manage the dyspeptic patient

A simple system which facilitates the verification of the calibration of iodine-125 sources in rigid absorbable suture, on the remote traceability basis, was developed. It consists of a plastic jig accommodating a sterile closed-end 16 gauge plastic catheter. The iodine-125 source in rigid absorbable suture is placed into the sterile closed-end 16 gauge plastic catheter. The jig fits in a standard dose calibrator. The sterility of the strand is maintained while a reasonable number of seeds used for an actual implant can be easily measured. This is an improvement over the current recommended practice of assaying just one separate seed of the same strength designation. This system brings the calibration procedure for the rigid sterile seed strands in line with the AAPM TG-40 recommendation for the rest of radioactive seed products.     

Optimization of permanent 125I prostate implants using fast simulated annealing

PURPOSE: Treatment planning of ultrasound-guided transperineal 125I permanent prostatic implants is a time-consuming task, due to the large number of seeds used and the very large number of possible source arrangements within the target volume. The goal of this work is to develop an algorithm based on fast simulated annealing allowing consistent and automatic dose distribution optimization in permanent 125I prostatic implants. METHODS AND MATERIALS: Fast simulated annealing is used to optimize the dose distribution by finding the best seed distribution through the minimization of a cost function. The cost function includes constraints on the dose at the periphery of the planned target volume and on the dose uniformity within this volume. Adjustment between peripheral dose and the dose uniformity can be achieved by varying the weight factor in the cost function. RESULTS: Fast simulated annealing algorithm finds very good seed distributions within 20,000 iterations. The computer time needed for the optimization of a typical permanent implant involving 60 seeds and 14 needles is approximately 15 min. An additional 5 min are necessary for isodose distribution computations and miscellaneous outputs. CONCLUSION: The use of fast simulated annealing allows for an efficient and rapid optimization of dose distribution. This algorithm is now routinely used at our institution in the clinical planning of 125I permanent transperineal prostate implants for early stage prostatic carcinoma.     

阻抑溴酚蓝褪色动力学光度法测定痕量钛（Ⅳ）

基于在盐酸介质中及热90℃的条件下, 痕量钛(Ⅳ)对高碘酸钾氧化溴酚蓝褪色反应有显著催化作用,据此建立了催化动力学光度法测定痕量钛(Ⅳ)的新分析方法。研究了最佳试验条件。在波长599nm处的吸光度差值△A与Ti(Ⅳ)的质量浓度ρ在0.10–2.0 ug./mL范围内呈良好的线性关系, 检出限为7.87×10-10 g/mL。对1 μg Ti（Ⅳ）/25 mL标准溶液测定12次,求得标准偏差为1.25%。测定了动力学参数,反应物钛(Ⅳ)是一级反应,在试验条件下,总反应为准一级反应,表观速率常数为5.85×10-4 /s,表观活化能为45.42 kJ/mol。该分析方法用于炼钢烧结矿1和烧结矿3中痕量钛(Ⅳ)的测定,样品中钛含量分别1.34%和4.30%与参照值吻合较好。RSD（n=6）为0.18% 和0.15% , 加标回收率在98%–101%范围,符合痕量分析要求。     

Michaelis-Menten kinetics determine cyclosporine steady-state concentrations: a population analysis in kidney transplant patients

Dosage adjustments of cyclosporine are confounded with an unexpected degree of variability, thus invalidating a direct proportionality between the oral dose rate and the steady-state concentration. In 1033 observations of dose rate and average steady-state concentration collected during therapeutic monitoring (area under the curve method) in 134 adult kidney transplant patients, a population pharmacokinetic analysis showed that a Michaelis-Menten model fitted the data better than a linear clearance model. It was further shown that the Michaelis-Menten constant (Km) parameter of the Michaelis-Menten model (the average steady-state concentration at half-maximal dose rate) increased during the first 4 months after transplantation whereas the maximal dose rate of the Michaelis-Menten model (Vmax) remained constant. The following parameters with interindividual variation in parenthesis were estimated: Vmax = 852 mg/24 hr (43%) and Km at 114 days after transplantation = 349 ng/ml (117%). An algorithm was derived from this population model that guides the clinician during the adjustment of oral cyclosporine dose rates.     

Two-dimensional scatter integration method for brachytherapy dose calculations in 3D geometry

In brachytherapy clinical practice, applicator shielding and tissue heterogeneities are usually not explicitly taken into account. None of the existing dose computational methods are able to reconcile accurate dose calculation in complex three-dimensional (3D) geometries with high efficiency and simplicity. We propose a new model that performs two-dimensional integration of the scattered dose component. The model calculates the effective primary dose at the point of interest and estimates the scatter dose as a superposition of the scatter contributions from pyramid-shaped minibeams. The approach generalizes a previous scatter subtraction model designed to calculate the dose for axial points in simple cylindrically symmetric geometry by dividing the scattering volume into spatial regions coaxial with the source-to-measurement point direction. To allow for azimuthal variation of the primary dose, these minibeams were divided into equally spaced azimuthally distributed pyramidal volumes. The model uses precalculated scatter-to-primary ratios (SPRs) for collimated isotropic sources. Effective primary dose, which includes the radiation scattered in the source capsule, is used to achieve independence from the source structure. For realistic models of the 192Ir HDR and PDR sources, the algorithm agrees with Monte Carlo within 2.5% and for the 125I type 6702 seed within 6%. The 2D scatter integration (2DSI) model has the potential to estimate the dose behind high-density heterogeneities both accurately and efficiently. The algorithm is much faster than Monte Carlo methods and predicts the dose around sources with different gamma-ray energies and differently shaped capsules with high accuracy.     

Benchmarking the MCNP code for Monte Carlo modelling of an in vivo neutron activation analysis system

The Monte Carlo computer code MCNP (version 4A) has been used to develop a personal computer-based model of the Swansea in vivo neutron activation analysis (IVNAA) system. The model included specification of the neutron source (252Cf), collimators, reflectors and shielding. The MCNP model was 'benchmarked' against fast neutron and thermal neutron fluence data obtained experimentally from the IVNAA system. The Swansea system allows two irradiation geometries using 'short' and 'long' collimators, which provide alternative dose rates for IVNAA. The data presented here relate to the short collimator, although results of similar accuracy were obtained using the long collimator. The fast neutron fluence was measured in air at a series of depths inside the collimator. The measurements agreed with the MCNP simulation within the statistical uncertainty (5-10%) of the calculations. The thermal neutron fluence was measured and calculated inside the cuboidal water phantom. The depth of maximum thermal fluence was 3.2 cm (measured) and 3.0 cm (calculated). The width of the 50% thermal fluence level across the phantom at its mid-depth was found to be the same by both MCNP and experiment. This benchmarking exercise has given us a high degree of confidence in MCNP as a tool for the design of IVNAA systems.     

Nicotinic acetylcholine receptor from rat brain. Solubilization, partial purification, and characterization

Nicotinic acetylcholine receptor protein (nAChR) has been solubilized from rat cerebral cortices by extracting a crude membrane fraction with the nonionic detergent Triton X-100 (polyoxyethylene-p-t-octylphenol). The solubilized nAChR was partially purified by affinity chromatography (Naja naja siamensis alpha-toxin affinity arm, linked to Sepharose 4B) and characterized by binding of 125I-labeled alpha-bungarotoxin. The reaction of labeled toxin and nAChR appears to be second order with a rate constant (k1) equal to 0.38 X 10(5) M-1 S-1 at 20 degrees. The toxin-nAChR complex dissociates with a dissociation rate constant (k-1) of 1.23 X 10(-5) S-1 at 20 degrees (t 1/2 = 15.6 h). The kinetically determined dissociation constant (Kd) for the complex is 3.24 X 10(-10) M. A variety of cholinergic ligands were studied for their ability to inhibit binding of labeled toxin. The results indicate that the brain receptor is indeed nicotinic. The s20, w and v of the toxin-nAChR complex in 0.1% Triton were determined by velocity sedimentation in D2O and H2O sucrose gradients. The values are 12.9 S and 0.80 cm3 g-1. The Stokes radius of the complex determined by gel filtration equals 7.5 nm. The Mr of the complex calculated from the hydrodynamic parameters, and corrected for bound detergent, equals 357,000.     

Magnetic resonance imaging of microbubbles in a superheated emulsion chamber for brachytherapy dosimetry

This paper describes development of magnetic resonance imaging (MRI) techniques for three-dimensional (3D) imaging of a position-sensitive detector for brachytherapy dosimetry. The detector is a 0.5 l chamber containing an emulsion of halocarbon-115 droplets in a tissue-equivalent glycerin-based gel. The halocarbon droplets are highly superheated and expand into vapor microbubbles upon irradiation. Brachytherapy sources can be inserted into the superheated emulsion chamber to create distributions of bubbles. Three-dimensional MRI of the chamber is then performed. A 3D gradient-echo technique was optimized for spatial resolution and contrast between bubbles and gel. Susceptibility gradients at the interfaces between bubbles and gel are exploited to enhance contrast so microscopic bubbles can be imaged using relatively large voxel sizes. Three-dimensional gradient-echo images are obtained with an isotropic resolution of 300 microns over a 77 mm x 77 mm x 9.6 mm field-of-view in an imaging time of 14 min. A post-processing technique was developed to semi-automatically segment the bubbles from the images and to assess dose distributions based on the measured bubble densities. Relative dose distributions are computed from MR images for a 125I brachytherapy source and the results compare favorably to relative radial dose distributions calculated as recommended by Task Group 43 of the American Association of Physicists in Medicine.