KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver.

BACKGROUND: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). METHODS: 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student's t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. RESULTS: Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student's t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. CONCLUSION: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Partial volume effect correction in PET using regularized iterative deconvolution with variance control based on local topology.

Correcting positron emission tomography (PET) images for the partial volume effect (PVE) due to the limited resolution of PET has been a long-standing challenge. Various approaches including incorporation of the system response function in the reconstruction have been previously tested. We present a post-reconstruction PVE correction based on iterative deconvolution using a 3D maximum likelihood expectation-maximization (MLEM) algorithm. To achieve convergence we used a one step late (OSL) regularization procedure based on the assumption of local monotonic behavior of the PET signal following Alenius et al. This technique was further modified to selectively control variance depending on the local topology of the PET image. No prior 'anatomic' information is needed in this approach. An estimate of the noise properties of the image is used instead. The procedure was tested for symmetric and isotropic deconvolution functions with Gaussian shape and full width at half-maximum (FWHM) ranging from 6.31 mm to infinity. The method was applied to simulated and experimental scans of the NEMA NU 2 image quality phantom with the GE Discovery LS PET/CT scanner. The phantom contained uniform activity spheres with diameters ranging from 1 cm to 3.7 cm within uniform background. The optimal sphere activity to variance ratio was obtained when the deconvolution function was replaced by a step function few voxels wide. In this case, the deconvolution method converged in approximately 3-5 iterations for most points on both the simulated and experimental images. For the 1 cm diameter sphere, the contrast recovery improved from 12% to 36% in the simulated and from 21% to 55% in the experimental data. Recovery coefficients between 80% and 120% were obtained for all larger spheres, except for the 13 mm diameter sphere in the simulated scan (68%). No increase in variance was observed except for a few voxels neighboring strong activity gradients and inside the largest spheres. Testing the method for patient images increased the visibility of small lesions in non-uniform background and preserved the overall image quality. Regularized iterative deconvolution with variance control based on the local properties of the PET image and on estimated image noise is a promising approach for partial volume effect corrections in PET.

The three-dimensional scintillation dosimetry method: test for a 106Ru eye plaque applicator.

The need for fast, accurate and high resolution dosimetric quality assurance in radiation therapy has been outpacing the development of new and improved 2D and 3D dosimetry techniques. This paper summarizes the efforts to create a novel and potentially very fast, 3D dosimetry method based on the observation of scintillation light from an irradiated liquid scintillator volume serving simultaneously as a phantom material and as a dose detector medium. The method, named three-dimensional scintillation dosimetry (3DSD), uses visible light images of the liquid scintillator volume at multiple angles and applies a tomographic algorithm to a series of these images to reconstruct the scintillation light emission density in each voxel of the volume. It is based on the hypothesis that with careful design and data processing, one can achieve acceptable proportionality between the local light emission density and the locally absorbed dose. The method is applied to a Ru-106 eye plaque immersed in a 16.4 cm3 liquid scintillator volume and the reconstructed 3D dose map is compared along selected profiles and planes with radiochromic film and diode measurements. The comparison indicates that the 3DSD method agrees, within 25% for most points or within approximately 2 mm distance to agreement, with the relative radiochromic film and diode dose distributions in a small (approximately 4.5 mm high and approximately 12 mm diameter) volume in the unobstructed, high gradient dose region outside the edge of the plaque. For a comparison, the reproducibility of the radiochromic film results for our measurements ranges from 10 to 15% within this volume. At present, the 3DSD method is not accurate close to the edge of the plaque, and further than approximately 10 mm (<10% central axis depth dose) from the plaque surface. Improvement strategies, considered important to provide a more accurate quick check of the dose profiles in 3D for brachytherapy applicators, are discussed.

Validation of Monte Carlo dose calculations near 125I sources in the presence of bounded heterogeneities.

PURPOSE: Dose distributions around low energy (< 60 keV) brachytherapy sources, such as 125I, are known to be very sensitive to changes in tissue composition. Available 125I dosimetry data describe the effects of replacing the entire water medium by heterogeneous material. This work extends our knowledge of tissue heterogeneity effects to the domain of bounded tissue heterogeneities, simulating clinical situations. Our goals are three-fold: (a) to experimentally characterize the variation of dose rate as a function of location and dimensions of the heterogeneity, (b) to confirm the accuracy of Monte Carlo dose calculation methods in the presence of bounded tissue heterogeneities, and (c) to use the Monte Carlo method to characterize the dependence of heterogeneity correction factors (HCF) on the irradiation geometry. METHODS AND MATERIALS: Thermoluminescent dosimeters (TLD) were used to measure the deviations from the homogeneous dose distribution of an 125I seed due to cylindrical tissue heterogeneities. A solid water phantom was machined accurately to accommodate the long axis of the heterogeneous cylinder in the transverse plane of a 125I source. Profiles were obtained perpendicular to and along the cylinder axis, in the region downstream of the heterogeneity. Measurements were repeated at the corresponding points in homogeneous solid water. The measured heterogeneity correction factor (HCF) was defined as the ratio of the detector reading in the heterogeneous medium to that in the homogeneous medium at that point. The same ratio was simulated by a Monte Carlo photon transport (MCPT) code, using accurate modeling of the source, phantom, and detector geometry. In addition, Monte Carlo-based parametric studies were performed to identify the dependence of HCF on heterogeneity dimensions and distance from the source. RESULTS: Measured and calculated HCFs reveal excellent agreement (< or = 5% average) over a wide range of materials and geometries. HCFs downstream of 20 mm diameter by 10 mm thick hard bone cylinders vary from 0.12 to 0.30 with respect to distance, while for an inner bone cylinder of the same dimension, it varies from 0.72 to 0.83. For 6 mm diameter by 10 mm thick hard bone and inner bone cylinders, HCF varies 0.27-0.58 and 0.77-0.88, respectively. For lucite, fat, and air, the dependence of HCF on the 3D irradiation geometry was much less pronounced. CONCLUSION: Monte Carlo simulation is a powerful, convenient, and accurate tool for investigating the long neglected area of tissue composition heterogeneity corrections. Simple one dimensional dose calculation models that depend only on the heterogeneity thickness cannot accurately characterize 125I dose distributions in the presence of bone-like heterogeneities.

Monte Carlo-aided dosimetry of the Source Tech Medical Model STM1251 I-125 interstitial brachytherapy source.

We have used Monte Carlo photon transport simulations to calculate the dosimetric parameters of a new 125I seed, the Source Tech Medical Model STM125I source for interstitial brachytherapy. We followed the recommendations of the AAPM Task Group 43 and determined the following parameters: dose-rate constant, radial dose function, anisotropy function, anisotropy factor, and anisotropy constant. The recently (January 1999) revised National Institute of Standards and Technology I-125 standard for air-kerma strength calibration was taken into account as well as updated interaction cross-section data. The calculated dose-rate constant, when normalized to the simulated wide-angle, free-air chamber measurement of air-kerma strength, is 0.980 cGy h(-1) U(-1). The calculated radial dose function for the Model STM 1251 source is more penetrating than that of the model 6711 seed (by 18% at 5 cm distance), but agrees closely (within statistical errors) with that of the model 6702 seed up to distances of 10 cm. The STM125I source anisotropy functions indicate that its dose distribution is somewhat more anisotropic than that of the model 6702 and 6711 seeds at 1 cm distance but is comparable at larger distances. The Model STM125I anisotropy constant is very similar to that of the model 6711, 6702, and MED363I A/M seeds.

Analytical approach to heterogeneity correction factor calculation for brachytherapy.

In brachytherapy treatment planning, the effects of tissue and applicator heterogeneities are commonly neglected due to lack of accurate, general, and fast three-dimensional (3D) dose-computational algorithms. A novel approach, based on analytical calculation of scattered photon fluxes inside and around a disk-shaped heterogeneity, has been developed for use in the three-dimensional scatter-subtraction algorithm. Specifically, our model predicts the central-ray dose distribution for a collimated photon isotropic source or brachytherapy "minibeam" in the presence of a slab of heterogeneous material. The model accounts for the lateral dimensions, location, composition, density, and thickness of the heterogeneity using precalculated scatter-to-primary ratios (SPRs) for the corresponding homogeneous problem. The model is applicable to the entire brachytherapy energy range (25 to 662 keV) and to a broad range of materials having atomic numbers of 13 to 82, densities of 2.7 g.cm-3 (Al) to 21.45 g.cm-3 (Pt) and thicknesses up to 1 mean free path. For this range of heterogeneous materials, the heterogeneity correction factors (HCFs) vary from 0.09 to 0.75. The model underestimates HCF when multiple scattering prevails and overestimates HCF when absorption dominates. However, the analytic model agrees with Monte Carlo photon transport (MCPT) benchmark calculations within 1.8% to 10% for 125I, 169Yb, 192Ir, and 137Cs for a wide variety of materials, with the exception of Ag. For 125I shielded by Ag, where the mean discrepancy can exceed 25%, the error is due to K-edge characteristic x rays originating within the heterogeneity. The proposed approach provides reductions in CPU time required of 5 x 10(4)-10(5) and 100 in comparison with direct MCPT simulation and 1D numerical integration, respectively. The limitations of model applicability, as determined by the physical properties of heterogeneity material and accuracy required, are also discussed.

Measurement and calculation of heterogeneity correction factors for an Ir-192 high dose-rate brachytherapy source behind tungsten alloy and steel shields.

Shields made of high atomic number material are commonly used in vaginal applicators with high dose-rate (HDR) 192Ir remotely afterloaded brachytherapy sources. However little data is available for the dose distribution around such shields. Heterogeneity correction factors (HCFs) are defined as the ratio of the dose to a point with the heterogeneity (shield) in place, divided by the dose to the same point with no heterogeneity. Using thermoluminescent dosimeters (TLDs) in solid water phantom we have measured the HCFs behind 6 and 20 mm diam tungsten alloy disks, 4 and 2 mm thick and a 4 mm thick steel disk, positioned 15 mm from the source. For each measurement point, the heterogeneity correction factors were also inferred from Monte Carlo simulations, which accurately modeled the experimental geometry. The agreement between measured and calculated HCFs on the average was within 6%. Tungsten alloy disks resulted in about two times greater dose reduction in water (HCF approximately 0.4, for 20 x 4 mm disk) than for a steel disk with the same dimensions (HCF approximately 0.85). Reducing the disk diameter to 6 mm increased the dose transmission up to about 25%. Increasing the source-to-detector distance from 4 to 7 cm caused a change in HCF from 2% to more than 20%, depending on disk material and diameter. The detector artifact effects arising from the finite size and different composition of the TLD chips were determined.

New water equivalent liquid scintillation solutions for 3D dosimetry.

Despite recent advances in radiochromic film and gel dosimetry techniques, radiation therapy still lacks an efficient, accurate, and convenient dose measurement method capable of measuring the dose simultaneously over a plane or a volume (3D). A possibility for creating such a 3D method based on observing scintillation photons emitted from an irradiated volume was recently reported [A. S. Kirov et al., Med. Phys. 26, 1069 (1999)]. In the present article, we investigate the potential to use a liquid scintillation solution (LS) as a dose sensitive media and, simultaneously, as a water equivalent phantom material which fills the measurement volume. We show that matching water density in addition to energy absorption properties is important for using the LS solution as a phantom. Through a parametric study of the LS attenuation and absorption coefficients as well as Monte Carlo dose calculations and scintillation efficiency measurements we developed novel LS materials. For the new solutions, the calculated dose in LS is within 8% of the dose to water for depths up to 5 cm for photons having energies between 30 keV and 2 MeV. The new LS solutions, which are loaded with a Si containing compound, retain more than 85% of the scintillation efficiency of the unloaded solutions and exhibit high localization of the scintillation process. The new LS solutions are superior with respect to efficiency and water equivalence to plastic scintillator materials used in dosimetry and may be used apart from the mentioned 3D method.

Quantitative evaluation of radiochromic film response for two-dimensional dosimetry.

Radiochromic film (RCF) is attractive as a thin, high resolution, 2D planar dosimeter. We have studied the uniformity, linearity, and reproducibility of a commercially supplied RCF system (model MD-55). Forty 12 cm long strips of RCF were exposed to uniform doses of 6 MV x rays. Optical density (OD) distributions were measured by a helium-neon scanning laser (633 nm) 2D densitometer and also with a manual densitometer. All film strips showed 8%-15% variations in OD values independent of densitometry technique which are evidently due to nonuniform dispersal of the sensor medium. A double exposure technique was developed to solve this problem. The film is first exposed to a uniform beam, which defines a pixel-by-pixel nonuniformity correction matrix. The film is then exposed to the unknown dose distribution, rescanned, and the net OD at each pixel corrected for nonuniformity. The double exposure technique reduces OD/unit dose variation to a 2%-5% random fluctuation. RCF response was found to deviate significantly from linearity at low doses (40% change in net OD/Gy from 1 to 30 Gy); a finding not previously reported. To study the tradeoff between statistical noise and spatial resolution, OD was averaged over blocks of adjacent 50 microns pixels (ranging from 1 x 1 to 10 x 10 pixels). Reproducibility, defined as the standard deviation of repeated single-pixel measurements on separate film pieces, was 2% at 30 Gy for a resolution of 0.25 mm. With careful correction for nonlinearity and nonuniformity, RCF is a promising quantitative 2D dosimeter for radiation oncology applications.

Quantitative optical densitometry with scanning-laser film digitizers.

A new process for eliminating two types of artifacts inherent in commercially available transmission scanning-laser film digitizers is presented. The first kind of artifact results in nonreproducible interference-pattern fluctuations as large as 7%. The second kind results in spreading of transmitted light from low-to-high optical density (OD) in regions with rapidly varying ODs, producing errors as large as 50%. These OD artifacts cause the loss of precision for films with low-OD regions (first type) and the loss of accuracy for films with regions of high-OD near high-OD gradients (second type). Test radiochromic films, produced by uniform exposure to a 6 MV photon beam and a high dose rate 192Ir brachytherapy source, along with test radiographic films were used to characterize the artifacts of a commercially available scanning-laser film digitizer. The interference-pattern artifact was eliminated by digitizing the films on a masked diffusing ground-glass scanning bed. The light-transmission artifact was eliminated through discrete-fast-Fourier-transform (DFFT) deconvolution of transmission profiles with measured digitizer line-spread functions. Obtaining precise OD distributions after the DFFT deconvolution required prior removal of the interference-pattern artifact and application of a low-pass Wiener noise filter. Light-transmission artifacts are particularly significant for applications requiring measurement of high-gradient OD distributions, such as brachytherapy or conformal photon-beam film dosimetry and quantitation of two-dimensional electrophoresis gels. Errors as large as 15%-35% occur in OD distributions representative of these applications. The data collection and correction process developed in this study successfully removes these artifacts.

Quantitative verification of 192Ir PDR and HDR source structure by pin-hole autoradiography.

For precise localization of the center and determination of the dimensions of the radioactive material within the capsule of brachytherapy sources, we have developed a method based on simultaneous pin-hole autoradiography of two sources. We constructed a variable magnification pin-hole camera consisting of two telescopically fitted Plexiglas cylinders which can accommodate two radioactive sources on the plate covering the top cylinder. The 192Ir pulsed and high dose-rate sources were studied and an 192Ir seed was used as a reference source. The magnification factor was determined from the dimensions of the 192Ir seed image, which was geometrically well defined by a separate transmission radiography experiment. The observed position for the center of radioactivity in the PDR and the HDR source capsules are in agreement with the vendor specifications. The distance from the tip of the PDR capsule to its center of radioactivity was found in this way to be 0.79 +/- 0.21 mm, which agrees with the position (0.85 mm) of the pellet situated closer to the tip as specified by the vendor. Quantitative verification of the internal source structure using this method enhances the accuracy with which the dose distribution near brachytherapy sources can be predicted by three-dimensional Monte Carlo calculations.

Towards two-dimensional brachytherapy dosimetry using plastic scintillator: new highly efficient water equivalent plastic scintillator materials.

Plastic scintillator (PS) has been proposed for both one- and two-dimensional (1D and 2D) dose measurements for radiation therapy applications. For low-energy photon modalities (e.g., brachytherapy), an efficient water equivalent scintillator is needed. To perform 2D measurements, a high localization of the scintillation process is required. Guided by comparison of the mass energy absorption coefficients as a function of energy and of the dose distribution as a function of distance from the radioactive source, as modeled by Monte Carlo photon transport simulation, a small quantity of medium atomic number (Z) atoms (4% Cl) was incorporated in a polyvinyl toluene (PVT) based PS to approximate closely (within 10%) the radiological properties of water in the 20-662 keV energy range. However, the scintillation efficiency of commercial PS mixtures drops as much as 70% when loaded with high atomic number additives. We developed experimental techniques to assess the scintillation efficiency and locality of 15 new PS mixtures. These mixtures differ by the type of the scintillation dyes and the type of compound containing the medium Z atoms (chlorine). To achieve higher material stability, 4-chlorostyrene was used as a loading compound to ensure polymerization with the PVT base. Two of the new PS materials exhibited scintillation efficiencies within 30% of one of the most efficient commercially available products (BC-400), which is not water equivalent at such low energies. These new scintillator materials are promising candidates for the development of an accurate and efficient radiation dosimetry method not only for brachytherapy, but also for superficial and diagnostic applications.

Experimental validation of Monte Carlo dose calculations about a high-intensity Ir-192 source for pulsed dose-rate brachytherapy.

Despite widespread use of high-intensity Ir-192 remotely afterloaded sources, no published measured or calculated dose-rate tables for currently used source designs are available. For a pulsed dose-rate Ir-192 source, both transverse axis (0.5-10 cm) and two-dimensional polar dose-rate profiles (1.5, 3, and 5 cm) were measured with thermoluminescent dosimetry in a solid water phantom. Dose rates were normalized to measured air-kerma strength, and the source geometry was verified by pinhole autoradiography and transmission radiography. At each measurement point, dose rates were calculated by a Monte Carlo photon transport (MCPT) code, which realistically modeled the experimental phantom, source, and detector geometry. Agreement between MCPT absolute dose-rate calculations and measurements averaged 3% and was less than 5%, demonstrating that Monte Carlo simulation is an accurate and powerful tool for two-dimensional dosimetric characterization of high activity Ir-192 sources.

Validation of a precision radiochromic film dosimetry system for quantitative two-dimensional imaging of acute exposure dose distributions.

We present an evaluation of the precision and accuracy of image-based radiochromic film (RCF) dosimetry performed using a commercial RCF product (Gafchromic MD-55-2, Nuclear Associates, Inc.) and a commercial high-spatial resolution (100 microm pixel size) He-Ne scanning-laser film-digitizer (Personal Densitometer, Molecular Dynamics, Inc.) as an optical density (OD) imaging system. The precision and accuracy of this dosimetry system are evaluated by performing RCF imaging dosimetry in well characterized conformal external beam and brachytherapy high dose-rate (HDR) radiation fields. Benchmarking of image-based RCF dosimetry is necessary due to many potential errors inherent to RCF dosimetry including: a temperature-dependent time evolution of RCF dose response; nonuniform response of RCF; and optical-polarization artifacts. In addition, laser-densitometer imaging artifacts can produce systematic OD measurement errors as large as 35% in the presence of high OD gradients. We present a RCF exposure and readout protocol that was developed for the accurate dosimetry of high dose rate (HDR) radiation sources. This protocol follows and expands upon the guidelines set forth by the American Association of Physicists in Medicine (AAPM) Task Group 55 report. Particular attention is focused on the OD imaging system, a scanning-laser film digitizer, modified to eliminate OD artifacts that were not addressed in the AAPM Task Group 55 report. RCF precision using this technique was evaluated with films given uniform 6 MV x-ray doses between 1 and 200 Gy. RCF absolute dose accuracy using this technique was evaluated by comparing RCF measurements to small volume ionization chamber measurements for conformal external-beam sources and an experimentally validated Monte Carlo photon-transport simulation code for a 192Ir brachytherapy source. Pixel-to-pixel standard deviations of uniformly irradiated films were less than 1% for doses between 10 and 150 Gy; between 1% and 5% for lower doses down to 1 Gy and 1% and 1.5% for higher doses up to 200 Gy. Pixel averaging to form 200-800 microm pixels reduces these standard deviations by a factor of 2 to 5. Comparisons of absolute dose show agreement within 1.5%-4% of dose benchmarks, consistent with a highly accurate dosimeter limited by its observed precision and the precision of the dose standards to which it is compared. These results provide a comprehensive benchmarking of RCF, enabling its use in the commissioning of novel HDR therapy sources.

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.

TLD, diode and Monte Carlo dosimetry of an 192Ir source for high dose-rate brachytherapy.

Very few dosimetry data are available for the current generation of high-dose-rate (HDR) 192Ir sources, which have broad application in remotely afterloaded brachytherapy. We have measured the two-dimensional dose rate distribution around a microSelectron-HDR source and used the results to validate Monte Carlo simulations. Thermoluminescent dosimeters (TLDs) in solid-water phantoms were used to measure the transverse-axis dose rates in the distance range 0.5-10 cm and the polar dose-rate profiles at 1.5, 3 and 5 cm distance from the source. At close distances, 2-40 mm from the HDR source, we performed transverse axis dose-rate measurements with a Si diode in water. We performed diode measurements at the same distances also for a pulsed dose-rate (PDR) source to compare the results for 192Ir sources with different encapsulation. Both the HDR and the PDR sources were decayed, separated from their cables and calibrated prior to the measurements. The measured dose rates were compared with Monte Carlo photon transport calculations, which realistically modelled the experimental and source geometry at each measurement point. Agreement between Monte Carlo photon transport absolute dose-rate calculations and measurements was, on average, within 5%. From the transverse-axis experimental data, we deduced a value for the dose-rate constant lambda 0 of 192Ir HDR sources of 1.14 cGy h-1 U-1 +/- 5%. This value agrees within the experimental error with the Monte Carlo estimate of 1.115 cGy h-1 U-1 +/- 0.5%. Excellent agreement with previously measured anisotropy functions was observed. Higher anisotropy is observed for the point at 0 degree along the source cable for which no previous data have been reported.

Plastic scintillator response to low-energy photons.

The plastic scintillator (PS) is a promising dosimeter for brachytherapy and other low-energy photon applications because of its high sensitivity and approximate tissue equivalence. As part of our project to develop a new PS material which maximizes sensitivity and radiological equivalence to water, we have measured the response, epsilon (light output/unit air kerma), of PS to low-energy bremsstrahlung (20 to 57 keV average energies) x-rays as well as photons emitted by 99mTc, 192Ir, and 137Cs sources, all of which were calibrated in terms of air kerma. The PS systems studied were a standard commercial PS, BC400 (Bicron Corporation, Newbury, OH), and our new sensitive and quench-resistant scintillator (polyvinyltoluene base and binary dye system) with and without 4% Cl loading intended to match the effective atomic number of water. For low-energy x-rays, epsilon was 20-57% relative to epsilon for 192Ir photons. Chlorine loading clearly reduced the energy dependence of epsilon, which ranged from 46% to 85% relative to 192Ir. However, even after using Monte Carlo photon-transport simulation to correct for the non-air equivalence of the PS, inherent dosimetric sensitivity still varied by 30% over the 20-400 keV energy range. Our work, one of the few measurements of PS response to low-energy photons, appears to confirm Birks' 1955 finding that ionization quenching reduces sensitivity to electrons below 125 keV. However, our results cannot be explained by Birks' widely used unimolecular quenching model.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

Using an external gating signal to estimate noise in PET with an emphasis on tracer avid tumors.

The purpose of this study is to establish and validate a methodology for estimating the standard deviation of voxels with large activity concentrations within a PET image using replicate imaging that is immediately available for use in the clinic. To do this, ensembles of voxels in the averaged replicate images were compared to the corresponding ensembles in images derived from summed sinograms. In addition, the replicate imaging noise estimate was compared to a noise estimate based on an ensemble of voxels within a region. To make this comparison two phantoms were used. The first phantom was a seven-chamber phantom constructed of 1 liter plastic bottles. Each chamber of this phantom was filled with a different activity concentration relative to the lowest activity concentration with ratios of 1:1, 1:1, 2:1, 2:1, 4:1, 8:1 and 16:1. The second phantom was a GE Well-Counter phantom. These phantoms were imaged and reconstructed on a GE DSTE PET/CT scanner with 2D and 3D reprojection filtered backprojection (FBP), and with 2D- and 3D-ordered subset expectation maximization (OSEM). A series of tests were applied to the resulting images that showed that the region and replicate imaging methods for estimating standard deviation were equivalent for backprojection reconstructions. Furthermore, the noise properties of the FBP algorithms allowed scaling the replicate estimates of the standard deviation by a factor of 1/square root N, where N is the number of replicate images, to obtain the standard deviation of the full data image. This was not the case for OSEM image reconstruction. Due to nonlinearity of the OSEM algorithm, the noise is shown to be both position and activity concentration dependent in such a way that no simple scaling factor can be used to extrapolate noise as a function of counts. The use of the Well-Counter phantom contributed to the development of a heuristic extrapolation of the noise as a function of radius in FBP. In addition, the signal-to-noise ratio for high uptake objects was confirmed to be higher with backprojection image reconstruction methods. These techniques were applied to several patient data sets acquired in either 2D or 3D mode, with (18)F (FLT and FDG). Images of the standard deviation and signal-to-noise ratios were constructed and the standard deviations of the tumors' uptake were determined. Finally, a radial noise extrapolation relationship deduced in this paper was applied to patient data.

Quantitative verification of 192 Ir PDR and HDR source structure by pin-hole autoradiography.

For precise localization of the center and determination of the dimensions of the radioactive material within the capsule of brachytherapy sources, we have developed a method based on simultaneous pin-hole autoradiography of two sources. We constructed a variable magnification pin-hole camera consisting of two telescopically fitted Plexiglas cylinders which can accommodate two radioactive sources on the plate covering the top cylinder. The 192 Ir pulsed and high dose-rate sources were studied and an 192 Ir seed was used as a reference source. The magnification factor was determined from the dimensions of the 192 Ir seed image, which was geometrically well defined by a separate transmission radiography experiment. The observed position for the center of radioactivity in the PDR and the HDR source capsules are in agreement with the vendor specifications. The distance from the tip of the PDR capsule to its center of radioactivity was found in this way to be 0.79±0.21 mm, which agrees with the position (0.85 mm) of the pellet situated closer to the tip as specified by the vendor. Quantitative verification of the internal source structure using this method enhances the accuracy with which the dose distribution near brachytherapy sources can be predicted by three-dimensional Monte Carlo calculations.