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Background: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. Aims: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. Materials and Methods: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. Results: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. Discussion: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. Conclusion: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application. Ministerio de Economía y Competitividad FPA2016-77689-C2-1-R National Institutes of Health U24CA215123 France-Greece PICS 8235 European Space Agency 4000126645/19/NL/BW Australian Research Council ARC DP170100967, DP170102423 Susan G Komen Foundation for the Cure IIR13262248

The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage – radiobiology, radiation physics, radiation protection and, in particular, medical physics – requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC)simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs)and double strand breaks (DSBs)in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%. © 2019 Associazione Italiana di Fisica Medica

Over the last decade one of the most significant technological advances made in the field of radiation detectors for nuclear medicine was the development of Silicon Photomultipler (SiPM) sensors. At present only a small number of SiPM based radiation detectors for Single Photon Emission Computed Tomography (SPECT) applications have been explored, and even fewer experimental prototypes developed. An in-silico investigation into the optimal design of a Philips DPC3200 SiPM photosensor-based thin monolithic scintillator detector for SPECT applications was undertaken using the Monte Carlo radiation transport modelling toolkit Geant4 version 10.5. The performance of the 20 different SPECT radiation detector configurations, 4 scintillator materials (NaI(Tl), GAGG(Ce), CsI(Tl) and LaBr3(Ce)) and 5 thicknesses (1–5 mm), were determined through the use of seven figures of merit. It was found that a crystal thickness range of 4–5 mm was required for all four materials to ensure acceptable energy resolution, sensitivity and spatial resolution performance with the Philips DPC3200 SiPM. Any thinner than this and the performance of all four materials was found to degrade rapidly due to a high probability of material specific fluorescence x-ray escape after incident gamma/x-ray photoelectric absorption. When factoring in each material's magnetic resonance imaging compatibility, hygroscopy, and cost, it was found that CsI(Tl) represents the most promising material to construct tileable Philips digital SiPM based thin monolithic scintillator detectors for SPECT applications.

International audience; The 3rd Geant4 International Conference at the Physics-Medicine-Biology Frontier, 29–31 October 2018, was organized in Bordeaux, France, by the Centre d'Etudes Nucléaires de Bordeaux-Gradignan (http://www.cenbg.in2p3.fr), a CNRS/IN2P3 and Bordeaux University research laboratory. The conference was chaired by Sébastien Incerti (CNRS/IN2P3, Bordeaux, France), with the support of two co-chairs Jeremy M. C. Brown (TUDelft, Delft, The Netherlands) and Susanna Guatelli (Wollongong University, Wollongong, Australia).

Neutron Computed Tomography (CT) is an increasingly utilised non-destructive analysis tool in material science, palaeontology, and cultural heritage. With the development of new neutron imaging facilities (such as DINGO, ANSTO, Australia) new opportunities arise to maximise their performance through the implementation of statistically driven image reconstruction methods which have yet to see wide scale application in neutron transmission tomography. This work outlines the implementation of a convex algorithm statistical image reconstruction framework applicable to the geometry of most neutron tomography instruments with the aim of obtaining similar imaging quality to conventional ramp filtered back-projection via the inverse Radon transform, but using a lower number of measured projections to increase object throughput. Through comparison of the output of these two frameworks using a tomographic scan of a known 3 material cylindrical phantom obtain with the DINGO neutron radiography instrument (ANSTO, Australia), this work illustrates the advantages of statistical image reconstruction techniques over conventional filter back-projection. It was found that the statistical image reconstruction framework was capable of obtaining image estimates of similar quality with respect to filtered back-projection using only 12.5% the number of projections, potentially increasing object throughput at neutron imaging facilities such as DINGO eight-fold.

International audience; We report on the recent progress within the Geant4 electromagnetic physics subpackages. Several new interfaces and models recently introduced are already used in LHC applications and may be useful for any type of simulation. Significant developments were carried out to improve the user interface, develop models of single and multiple scattering, and validate high energy models. Part of these developments are included in the Geant4 10.2 release and the full set are available in the new version 10.3 of December, 2016.

Laplacian Erosion, an image deblurring technique for multi-plane Gamma-cameras, has been developed and tested for planar imaging using a GEANT4 Monte Carlo model of the Pixelated Emission Detector for RadioisOtopes (PEDRO) as a test platform. A contrast and Derenzo-like phantom composed of 125I were both employed to investigate the dependence of detection plane and pinhole geometry on the performance of Laplacian Erosion. Three different pinhole geometries were tested. It was found that, for the test system, the performance of Laplacian Erosion was inversely proportional to the detection plane offset, and directly proportional to the pinhole diameter. All tested pinhole geometries saw a reduction in the level of image blurring associated with the pinhole geometry. However, the reduction in image blurring came at the cost of signal to noise ratio in the image. The application of Laplacian Erosion was shown to reduce the level of image blurring associated with pinhole geometry and improve recovered image quality in multi-plane Gamma-cameras for the targeted radiotracer 125I.

International audience; At very low radiation dose rates, the effects of energy depositions in cells by ionizing radiation is best understood stochastically, as ionizing particles deposit energy along tracks separated by distances often much larger than the size of cells. We present a thorough analysis of the stochastic impact of the natural radiative background on cells, focusing our attention on E. coli grown as part of a long term evolution experiment in both underground and surface laboratories. The chance per day that a particle track interacts with a cell in the surface laboratory was found to be 6 × 10−5 day−1, 100 times less than the expected daily mutation rate for E. coli under our experimental conditions. In order for the chance cells are hit to approach the mutation rate, a gamma background dose rate of 20 μGy hr−1 is predicted to be required.

Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here., Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 835, ISSN:0168-9002, ISSN:1872-9576

We present the outcomes of combined feasibility studies carried out at Elettra and Australian Synchrotron to evaluate novel protocols for threedimensional (3D) mammographic phase contrast imaging. A custom designed plastic phantom and some tissue samples have been studied at diverse resolution scales and experimental conditions. Several computed tomography (CT) reconstruction algorithms with different pre-processing and post-processing steps have been considered. Special attention was paid to the effect of phase retrieval on the diagnostic value of the reconstructed images. The images were quantitatively evaluated using objective quality indices in comparison with subjective assessments performed by three experienced radiologists and one pathologist. We show that the propagation-based phase-contrast imaging (PBI) leads to substantial improvement to the contrast-to-noise and to the intrinsic quality of the reconstructed CT images compared with conventional techniques as well as to an important reduction of the delivered doses, thus opening the way to clinical implementations.

The Pixelated Emission Detector for RadiOisotopes (PEDRO) is a hybrid imaging system designed for the measurement of single photon emission from small animal models. The proof-of-principle device consists of a Compton-camera situated behind a mechanical collimator and is intended to provide optimal detection characteristics over a broad spectral range, from 30 to 511 keV. An automated routine has been developed for the optimization of large-area slits in the outer regions of a collimator which has a central region allocated for pinholes. The optimization was tested with a GEANT4 model of the experimental prototype. The data were blurred with the expected position and energy resolution parameters and a Bayesian interaction ordering algorithm was applied. Images were reconstructed using cone back-projection. The results show that the optimization technique allows the large-area slits to both sample fully and extend the primary field of view (FoV) determined by the pinholes. The slits were found to provide truncation of the back-projected cones of response and also an increase in the success rate of the interaction ordering algorithm. These factors resulted in an increase in the contrast and signal-to-noise ratio of the reconstructed image estimates. Of the two configurations tested, the cylindrical geometry outperformed the square geometry, primarily because of a decrease in artifacts. This was due to isotropic modulation of the cone surfaces, that can be achieved with a circular shape. Also, the cylindrical geometry provided increased sampling of the FoV due to more optimal positioning of the slits. The use of the cylindrical collimator and application of the transmission function in the reconstruction was found to improve the resolution of the system by a factor of 20, as compared to the uncollimated Compton camera. Although this system is designed for small animal imaging, the technique can be applied to any application of single photon imaging.

The Pixelated Emission Detector for RadiOisotopes (PEDRO) is a hybrid imager designed for the measurement of single photon emission from small animals. The proof-of-principle device currently under development consists of a Compton-camera situated behind a mechanical modulator. The combination of mechanical and electronic (hybrid) collimation should provide optimal detection characteristics over a broad spectral range ( 30 keV ≤ E γ ≤ 511 keV ) , through a reduction in the sensitivity-resolution trade-off, inherent in conventional mechanically collimated configurations. This paper presents GEANT4 simulation results from the PEDRO geometry operated only as a Compton camera in order to gauge its advantage when used in concert with mechanical collimation—regardless of the collimation pattern. The optimization of multiple detector spacing and resolution parameters is performed utilizing the Median Distance of Closest Approach (MDCA) and has been shown to result in an optimum distance, beyond which only a loss in sensitivity occurs.

Results are presented of a recent experiment at the Imaging and Medical beamline of the Australian Synchrotron intended to contribute to the implementation of low-dose high-sensitivity three-dimensional mammographic phase-contrast imaging, initially at synchrotrons and subsequently in hospitals and medical imaging clinics. The effect of such imaging parameters as X-ray energy, source size, detector resolution, sample-to-detector distance, scanning and data processing strategies in the case of propagation-based phase-contrast computed tomography (CT) have been tested, quantified, evaluated and optimized using a plastic phantom simulating relevant breast-tissue characteristics. Analysis of the data collected using a Hamamatsu CMOS Flat Panel Sensor, with a pixel size of 100 µm, revealed the presence of propagation-based phase contrast and demonstrated significant improvement of the quality of phase-contrast CT imaging compared with conventional (absorption-based) CT, at medically acceptable radiation doses.

BACKGROUND: A marked elevation of serum leptin is observed soon after the start of peritoneal dialysis (PD), suggesting that leptin production may be stimulated by this treatment. Glucose metabolism is the major factor regulating leptin. The current study was designed to test if glucose-based PD fluids might regulate leptin production in vitro. METHODS: 3T3-L1 adipocytes were exposed to a 50:50 mixture of dialysis solutions and medium M199 containing 10% serum for

AGeant4Monte Carlo simulation of the X-ray fluorescence microprobe (XFM) end-station at the Australian Synchrotron has been developed. The simulation is required for optimization of the scan configuration and reconstruction algorithms. As part of the simulation process, a Gaussian beam model was developed. Experimental validation of this simulation has tested the efficacy for use of the low-energy physics models inGeant4for this synchrotron-based technique. The observed spectral distributions calculated in the 384 pixel Maia detector, positioned in the standard back-scatter configuration, were compared with those obtained from experiments performed at three incident X-ray beam energies: 18.5, 11.0 and 6.8 keV. The reduced χ-squared (\chi^{2}_{\rm{red}}) was calculated for the scatter and fluorescence regions of the spectra and demonstrates that the simulations successfully reproduce the scatter distributions. Discrepancies were shown to occur in the multiple-scatter tail of the Compton continuum. The model was shown to be particularly sensitive to the impurities present in the beryllium window of the Maia detector and their concentrations were optimized to improve the \chi^{2}_{\rm{red}} parameterization in the low-energy fluorescence regions of the spectra.

Marked hyperleptinaemia and metabolic acidosis are common findings in patients with chronic renal failure. In animal models, both leptin administration and acidosis reduce food intake. However, leptin causes loss of body fat, while acidosis induces muscle wasting. Whether a low pH and leptin production are related has not been studied. Leptin secretion was measured in cultured 3T3-L1 adipocytes exposed to acid or control pH for up to 96 h. In addition, serum leptin was compared between acidotic and bicarbonate-treated uraemic Wistar rats using the remnant model. Leptin levels in the culture medium were decreased at an acid pH of 7.1 compared with a control pH of 7.5 at 96 h (562±78 and 831±103 pg·48 h-1·well-1 respectively; mean±S.E.M.; P = 0.037). Similarly, serum leptin in uraemic rats was found to be lower in the acidotic group than in the bicarbonate-treated group, although this observation fell just short of statistical significance (1273±171 compared with 2059±376 pg/ml; P = 0.07). In conclusion, acidosis decreases leptin secretion from cultured adipocytes. Accordingly, acidotic uraemic rats seem to exhibit lower serum leptin levels than their bicarbonate-supplemented counterparts. This study is the first report providing a link between acidosis and leptin levels.

BACKGROUND Glomerulosclerosis and interstitial fibrosis, which are cardinal features of the end-stage kidney, result from accumulation of extracellular matrix proteins, particularly collagen, in the glomerular mesangium and renal interstitium. This study examined the effect of D-penicillamine (DPC), which inhibits collagen deposition, on disease progression in the remnant kidney. METHODS Two groups of 10 rats underwent two-thirds nephrectomy and were pair-fed 20% casein paste (Gp 1) or the same paste supplemented with 90 mg/kg body wt per day of DPC (Gp 2). Two further groups of five non-nephrectomized animals also received 20% casein paste either alone (Gp 3) or supplemented with DPC (Gp 4). In a further experiment, systolic blood pressure was compared at 1 and 4 weeks after nephrectomy in eight DPC-treated remnants and eight untreated controls. RESULTS Gp 2 developed significantly less proteinuria than Gp 1 (41 +/- 9 vs 142 +/- 33 mg/24 h at 6 weeks, P < 0.005; 136 +/- 36 vs 282 +/- 59 mg/24 h at 12 weeks, P < 0.05). At sacrifice after 12 weeks, glomerular filtration rates were higher (1.34 +/- 0.08 vs 1.07 +/- 0.1 ml/min, P < 0.05), kidney total collagen content was lower (14.9 +/- 1.5 vs 26.9 +/- 5.4 mg/kidney, P < 0.05) and glomerular abnormalities, interstitial fibrosis and lymphocytic infiltration were less marked in Gp 2 compared with Gp 1. DPC had no effect on protein excretion, total kidney collagen or GFR in non-nephrectomized rats, and did not influence the early rise in blood pressure seen after two-thirds nephrectomy. CONCLUSIONS These findings demonstrate that DPC reduces renal injury in the remnant kidney, and raise the possibility of a therapeutic role for DPC in the treatment of patients with chronic renal failure.

Monte Carlo based radiation transport modelling is a useful tool in evaluating the interaction and effect of radiation in a defined environment. The process of simulating Compton scattering is of interest in a large number of different fields. Of the range of available Monte Carlo radiation transport programs, Geant4, one of the most popular, integrated the effects of Doppler broadening into their standard low energy Compton scattering package in 2008. However, there still exists a significant limitation within this standard Compton scattering package regarding the algorithms that determine the emission direction of Compton electrons. Here we outline the development of the Monash University Low Energy Compton Scattering (MULECS) package. The package addresses the current limitation of Compton electron directionality of Geant4 through the inclusion of additional directional information of the pre-collision momentum. MULECS is intended to replace the standard Compton scattering package of Geant4 to improve the accuracy of emission imaging simulations below 2 MeV.

Compton reconstruction requires the computationally intensive, yet highly parallelizable, task of Cone of Response (CoR) back-projection. The acceleration of CoR back-projection is of significant importance as a faster algorithm allows the user to increase either the size or resolution of the imaging volume. Such acceleration also lends itself to the realization of real-time reconstruction. The image estimate is formed by calculating and histogramming voxel-cone intersections in the imaging volume. As the level of computation increases with the cube of the length or resolution of the volume, the bottle-neck in processing the dataset is at the imaging-voxel level, as opposed to the event level. The reconstruction algorithm developed for the Pixelated Emission Detector for RadiOisotopes (PEDRO) system was optimized for threading at the voxel level and implemented in the C++ programming language. The benchmark C++ code was then extended with OpenCL to assess the acceleration that could be obtained by running the algorithm on a selection of commercially available Graphical Processing Units (GPUs). Increases of up to 102 times the bench-mark speed were achieved

The Pixelated Emission Detector for RadiOisotopes (PEDRO) is a hybrid imaging system designed for the measurement of single photon emission from small animal models. The proof-of-principle device consists of a Compton-camera situated behind a mechanical collimator and is intended to provide optimal detection characteristics over a broad spectral range, from 30 keV to 511 keV. An automated routine has been developed for the optimization of the mechanical collimator which consists of pinholes and open slits. The optimization was tested with a Geant4 model of the experimental prototype. The data were blurred with the expected position and energy resolution parameters and a Bayesian interaction ordering algorithm was applied. The results show that the optimization technique allows the large-area slits to sample fully the primary field of view (FoV). The slits were found to provide truncation of the back-projected cones of response and also an increase in the success rate of the interaction ordering algorithm. These factors resulted in an increase in the contrast and signal-to-noise ratios of the reconstructed image estimates.

In severe chronic renal failure (CRF) with associated metabolic acidosis, abnormalities in protein metabolism and amino acid (AA) profiles in the fed state are well described. To evaluate the effect of early uraemia and the influence of acid-base status on protein metabolism and AA profiles, three groups of pair-fed rats were studied: group I - rats with 1+ 1/2 nephrectomy; group II - rats with 1+ 1/2 nephrectomy receiving NaHCO3 supplementation, and group III - sham-operated rats with NaHCO3 supplementation. After 4 weeks, serum creatinine values were similar in groups I and II (111 +/- 5 and 119 +/- 4 mumol/l) and higher than in group III (51 +/- 5 mumol/l, p0.0001); HCO-3 was reduced only in group I (22.4 +/- 0.8 mmol/l) compared to group II (28.3 +/- 0.6 mmol/l, p0.001) and group III (28.2 +/- 1.3 mmol/l, p0.001). In the uraemic animals (groups I and II) arterial AA profiles showed increased levels of phenylalanine, glycine, glutamate, proline and alanine. The marked increase of threonine in group I was corrected by NaHCO3 supplementation in group II. The total nonessential AA were higher both in group I (1,832 +/- 53 mumol/l, p0.05) and group II (1,788 +/- 103 mumol/l, p0.05) than in group III (1,542 +/- 54 mumol/l). These results are similar to those described in the fed state of uraemic patients. Intracellular AA changes were detected, especially in group II namely increased glycine and a decrease in threonine and serine levels. No signs of malnutrition or changes in alkali-soluble protein (ASP) or ASP/DNA ratio in liver and muscle were observed. These results show that AA abnormalities in the fed state occur early in the course of CRF, and that the marked increase of threonine is corrected by NaHCO3 supplementation. These data suggest that either an impaired utilization of the ingested proteins might occur before the appearance of major alterations in endogenous protein metabolism or acid-base status might alter AA metabolic rate per se.