New models for PIXE simulation with Geant4

Particle induced X-ray emission (PIXE) is a physical effect that is not yet adequately modelled in Geant4. The current status as in Geant4 9.2 release is reviewed and new developments are described. The capabilities of the software prototype are illustrated in application to the shielding of the X-ray detectors of the eROSITA telescope on the upcoming Spectrum-X-Gamma space mission.Comment: To be published in the Proceedings of the CHEP (Computing in High Energy Physics) 2009 conferenc

The Geant4-DNA project

The Geant4-DNA project proposes to develop an open-source simulation software based and fully included in the general-purpose Geant4 Monte Carlo simulation toolkit. The main objective of this software is to simulate biological damages induced by ionising radiation at the cellular and sub-cellular scale. This project was originally initiated by the European Space Agency for the prediction of deleterious effects of radiation that may affect astronauts during future long duration space exploration missions. In this paper, the Geant4-DNA collaboration presents an overview of the whole ongoing project, including its most recent developments already available in the last Geant4 public release (9.3 BETA), as well as an illustration example simulating the direct irradiation of a chromatin fibre. Expected extensions involving several research domains, such as particle physics, chemistry and cellular and molecular biology, within a fully interdiciplinary activity of the Geant4 collaboration are also discussed.Comment: presented by S. Incerti at the ASIA SIMULATION CONFERENCE 2009, October 7-9, 2009, Ritsumeikan University, Shiga, Japa

Geant4 physics processes for microdosimetry simulation: design foundation and implementation of the first set of models

New physical processes specific for microdosimetry simulation are under development in the Geant4 Low Energy Electromagnetic package. The first set of models implemented for this purpose cover the interactions of electrons, protons and light ions in liquid water; they address a physics domain relevant to the simulation of radiation effects in biological systems, where water represents an important component. The design developed for effectively handling particle interactions down to a low energy scale and the physics models implemented in the first public release of the software are described

Models of biological effects of radiation in the Geant4 toolkit

A project, named Geant4-DNA, is in progress to extend the Geant4 simulation toolkit to model the effects of radiation with biological systems at cellular and DNA level. The first component implemented in the first development cycle of the project describes the fractional survival of a population of cells irradiated with photons or charged particles. The software system developed provides the user the option to choose among a small set of alternative models for the calculation of mammalian cell survival after irradiation. The flexible design adopted makes the system open to further extension to implement other cell survival models available in literature. The preliminary design of a prototype of the cell survival models implemented and preliminary results in some selected cell lines are described

Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons

© 2018, The Author(s). This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs

Quantitative Genetic Analyses of Postcanine Morphological Crown Variation

Objectives: This article presents estimates of narrow-sense heritability and bivariate genetic correlation for 14 tooth crown morphological variants scored on permanent premolars, first molars, and second molars. The objective is to inform data collection and analytical practices in dental biodistance and to provide insights on the development of molar crowns as integrated structures. Materials and Methods: African American dental casts from the Menegaz-Bock collection were recorded for the Arizona State University Dental Anthropology System. Estimates of narrow-sense heritability and genetic correlation were generated using SOLAR v.8.1.1, which included assessment of age, sex, and birth year as covariates. Both continuous scale and dichotomized estimates are provided. Results: Heritability estimates were nonsignificant for the majority of variables; however, for variables yielding significant estimates, values were moderate to high in magnitude and comparable to previous studies. Comparing left and right-side heritability estimates suggests directional asymmetry in the expression of environmental variance, something not seen in anterior tooth traits. Genetic correlations were moderate among antimeres and metameres and low for different traits scored on the same tooth crown. Although several negative correlations were noted, few reached statistical significance. Results affirm some of the current data cleaning and analytical practices in dental biodistance, but others are called into question. These include the pooling of males and females and combining left and right-side data into a single dataset. Conclusions: In comparison to anterior tooth crown traits, postcanine heritabilities were more often non-significant; however, those traits with significant heritability also tended to produce higher estimates. Genetic correlations were unremarkable, in part, because they were underpowered. However, M1 results may provide insight into the complex relationship between genes, environment, and development in determining ultimate crown form

Small beams, fast predictions: a comparison of machine learning dose prediction models for proton minibeam therapy

Background: Dose calculations for novel radiotherapy cancer treatments such as proton minibeam radiation therapy is often done using full Monte Carlo (MC) simulations. As MC simulations can be very time consuming for this kind of application, deep learning models have been considered to accelerate dose estimation in cancer patients. Purpose: This work systematically evaluates the dose prediction accuracy, speed and generalization performance of three selected state-of-the-art deep learning models for dose prediction applied to the proton minibeam therapy. The strengths and weaknesses of those models are thoroughly investigated, helping other researchers to decide on a viable algorithm for their own application. Methods: The following recently published models are compared: first, a 3D U-Net model trained as a regression network, second, a 3D U-Net trained as a generator of a generative adversarial network (GAN) and third, a dose transformer model which interprets the dose prediction as a sequence translation task. These models are trained to emulate the result of MC simulations. The dose depositions of a proton minibeam with a diameter of 800μm and an energy of 20–100 MeV inside a simple head phantom calculated by full Geant4 MC simulations are used as a case study for this comparison. The spatial resolution is 0.5 mm. Special attention is put on the evaluation of the generalization performance of the investigated models. Results: Dose predictions with all models are produced in the order of a second on a GPU, the 3D U-Net models being fastest with an average of 130 ms. An investigated 3D U-Net regression model is found to show the strongest performance with overall 61.0%±0.5% of all voxels exhibiting a deviation in energy deposition prediction of less than 3% compared to full MC simulations with no spatial deviation allowed. The 3D U-Net models are observed to show better generalization performance for target geometry variations, while the transformer-based model shows better generalization with regard to the proton energy. Conclusions: This paper reveals that (1) all studied deep learning models are significantly faster than non-machine learning approaches predicting the dose in the order of seconds compared to hours for MC, (2) all models provide reasonable accuracy, and (3) the regression-trained 3D U-Net provides the most accurate predictions

Radiation dose enhancement at tissue-tungsten interfaces in HDR brachytherapy

© 2014 Institute of Physics and Engineering in Medicine. HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an 192Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HD

BrachyView, A novel inbody imaging system for HDR prostate brachytherapy: Design and Monte Carlo feasibility study

Purpose: High dose rate (HDR) brachytherapy is a form of radiation therapy for treating prostate cancer whereby a high activity radiation source is moved between predefined positions inside applicators inserted within the treatment volume. Accurate positioning of the source is essential in delivering the desired dose to the target area while avoiding radiation injury to the surrounding tissue. In this paper, HDR BrachyView, a novel inbody dosimetric imaging system for real time monitoring and verification of the radioactive seed position in HDR prostate brachytherapy treatment is introduced. The current prototype consists of a 15 × 60 mm2 silicon pixel detector with a multipinhole tungsten collimator placed 6.5 mm above the detector. Seven identical pinholes allow full imaging coverage of the entire treatment volume. The combined pinhole and pixel sensor arrangement is geometrically designed to be able to resolve the three-dimensional location of the source. The probe may be rotated to keep the whole prostate within the transverse plane. The purpose of this paper is to demonstrate the efficacy of the design through computer simulation, and to estimate the accuracy in resolving the source position (in detector plane and in 3D space) as part of the feasibility study for the BrachyView project. Methods: Monte Carlo simulations were performed using the GEANT4 radiation transport model, with a 192Ir source placed in different locations within a prostate phantom. A geometrically accurate model of the detector and collimator were constructed. Simulations were conducted with a single pinhole to evaluate the pinhole design and the signal to background ratio obtained. Second, a pair of adjacent pinholes were simulated to evaluate the error in calculated source location. Results: Simulation results show that accurate determination of the true source position is easily obtainable within the typical one second source dwell time. The maximum error in the estimated projection position was found to be 0.95 mm in the imaging (detector) plane, resulting in a maximum source positioning estimation error of 1.48 mm. Conclusions: HDR BrachyView is a feasible design for real-time source tracking in HDR prostate brachytherapy. It is capable of resolving the source position within a subsecond dwell time. In combination with anatomical information obtained from transrectal ultrasound imaging, HDR BrachyView adds a significant quality assurance capability to HDR brachytherapy treatment systems. © 2013 American Association of Physicists in Medicine

Vpu Antagonizes BST-2–Mediated Restriction of HIV-1 Release via β-TrCP and Endo-Lysosomal Trafficking

The interferon-induced transmembrane protein BST-2/CD317 (tetherin) restricts the release of diverse enveloped viruses from infected cells. The HIV-1 accessory protein Vpu antagonizes this restriction by an unknown mechanism that likely involves the down-regulation of BST-2 from the cell surface. Here, we show that the optimal removal of BST-2 from the plasma membrane by Vpu requires the cellular protein β-TrCP, a substrate adaptor for a multi-subunit SCF E3 ubiquitin ligase complex and a known Vpu-interacting protein. β-TrCP is also required for the optimal enhancement of virion-release by Vpu. Mutations in the DSGxxS β-TrCP binding-motif of Vpu impair both the down-regulation of BST-2 and the enhancement of virion-release. Such mutations also confer dominant-negative activity, consistent with a model in which Vpu links BST-2 to β-TrCP. Optimal down-regulation of BST-2 from the cell surface by Vpu also requires the endocytic clathrin adaptor AP-2, although the rate of endocytosis is not increased; these data suggest that Vpu induces post-endocytic membrane trafficking events whose net effect is the removal of BST-2 from the cell surface. In addition to its marked effect on cell-surface levels, Vpu modestly decreases the total cellular levels of BST-2. The decreases in cell-surface and intracellular BST-2 are inhibited by bafilomycin A1, an inhibitor of endosomal acidification; these data suggest that Vpu induces late endosomal targeting and partial degradation of BST-2 in lysosomes. The Vpu-mediated decrease in surface expression is associated with reduced co-localization of BST-2 and the virion protein Gag along the plasma membrane. Together, the data support a model in which Vpu co-opts the β-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor