Investigation of hydrogen peroxide yields and oxygen consumption in high dose rate irradiation: a TOPAS-nBio Monte Carlo study.

TOPAS-nBio enables users to simulate dose rate-dependent radiation chemical yields in water radiolysis accounting for inter-track and long-term chemistry for pulsed irradiation. This study aims to extend the TOPAS-nBio chemistry for the special case of continuous high-dose rate scenario, where both intertrack and longer time reactions need to be considered, and to quantitatively validate the extended framework by comparing the results with experimental data.The inter-track chemistry and escape-values were first evaluated by the independent reaction time method.

Modeling the oxygen effect in DNA strand break induced by gamma-rays with TOPAS-nBio.

To present and validate a method to simulate from first principles the effect of oxygen on radiation-induced double-strand breaks (DSBs) using the Monte Carlo Track-structure code TOPAS-nBio.Two chemical models based on the oxygen fixation hypothesis (OFH) were developed in TOPAS-nBio by considering an oxygen adduct state of DNA and creating a competition kinetic mechanism between oxygen and the radioprotective molecule WR-1065. We named these models 'simple' and 'detailed' due to the way they handle the hydrogen abstraction pathways.

TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level.

This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm) irradiated by MV X-rays at several absorbed dose values from 0-8 Gy.

An interface tool to parametrize treatment plans for the TrueBeam radiotherapy system into TOPAS parameter control files for Monte Carlo simulation.

Purpose: The Monte Carlo (MC) method, the gold standard method for radiotherapy dose calculations, is underused in clinical research applications mainly due to computational speed limitations. Another reason is the time-consuming and error prone conversion of treatment plan specifications into MC parameters. To address this issue, we developed an interface tool that creates a set of TOPAS parameter control files (PCF) from information exported from a clinical treatment planning system (TPS) for plans delivered by the TrueBeam radiotherapy system.

A framework for in-field and out-of-field patient specific secondary cancer risk estimates from treatment plans using the TOPAS Monte Carlo system.

. To allow the estimation of secondary cancer risks from radiation therapy treatment plans in a comprehensive and user-friendly Monte Carlo (MC) framework..

Lithium inelastic cross-sections and their impact on micro and nano dosimetry of boron neutron capture.

To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV u. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques.The Classical Trajectory Monte Carlo method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV uto 10 MeV u.

TOPAS simulation of photoneutrons in radiotherapy: accuracy and speed with variance reduction.

. We provide optimal particle split numbers for speeding up TOPAS Monte Carlo simulations of linear accelerator (linac) treatment heads while maintaining accuracy. In addition, we provide a new TOPAS physics module for simulating photoneutron production and transport.

Creating uniform cluster dose spread-out Bragg peaks for proton and carbon beams.

Background: Preliminary data have shown a close association of the generalized ionization cluster size dose (in short, cluster dose) with cell survival, independent of particle type, and energy, when cluster dose is derived from an ionization detail parameter preferred for its association with cell survival. Such results suggest cluster dose has the potential to replace RBE-weighted dose in proton and ion beam radiotherapy treatment plan optimization, should a uniform cluster dose lead to comparable biological effects. However, further preclinical investigations are warranted to confirm this premise.

A digital male pelvis phantom series showing anatomical variations over the course of fractionated radiotherapy treatment.

Background: Daily IGRT images show day-to-day anatomical variations in patients undergoing fractionated prostate radiotherapy. This is of particular importance in particle beam treatments.

Purpose: To develop a digital phantom series showing variation in pelvic anatomy for evaluating treatment planning and IGRT procedures in particle radiotherapy.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy.

. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP)..

An integrated Monte Carlo track-structure simulation framework for modeling inter and intra-track effects on homogenous chemistry.

. The TOPAS-nBio Monte Carlo track structure simulation code, a wrapper of Geant4-DNA, was extended for its use in pulsed and longtime homogeneous chemistry simulations using the Gillespie algorithm..

TOPAS-imaging: extensions to the TOPAS simulation toolkit for medical imaging systems.

. The TOol for PArticle Simulation (TOPAS) is a Geant4-based Monte Carlo software application that has been used for both research and clinical studies in medical physics. So far, most users of TOPAS have focused on radiotherapy-related studies, such as modeling radiation therapy delivery systems or patient dose calculation.

Impact of DNA Geometry and Scoring on Monte Carlo Track-Structure Simulations of Initial Radiation-Induced Damage.

Track structure Monte Carlo simulations are a useful tool to investigate the damage induced to DNA by ionizing radiation. These simulations usually rely on simplified geometrical representations of the DNA subcomponents. DNA damage is determined by the physical and physicochemical processes occurring within these volumes.

TOPAS-nBio simulation of temperature-dependent indirect DNA strand break yields.

Current Monte Carlo simulations of DNA damage have been reported only at ambient temperature. The aim of this work is to use TOPAS-nBio to simulate the yields of DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) produced in plasmids under low-LET irradiation incorporating the effect of the temperature changes in the environment. A new feature was implemented in TOPAS-nBio to incorporate reaction rates used in the simulation of the chemical stage of water radiolysis as a function of temperature.

DNA damage modeled with Geant4-DNA: effects of plasmid DNA conformation and experimental conditions.

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated byCo orCs-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling.

TOPAS-nBio validation for simulating water radiolysis and DNA damage under low-LET irradiation.

The chemical stage of the Monte Carlo track-structure simulation code Geant4-DNA has been revised and validated. The root-mean-square (RMS) empirical parameter that dictates the displacement of water molecules after an ionization and excitation event in Geant4-DNA has been shortened to better fit experimental data. The pre-defined dissociation channels and branching ratios were not modified, but the reaction rate coefficients for simulating the chemical stage of water radiolysis were updated.

Dispersion calibration for the National Ignition Facility electron-positron-proton spectrometers for intense laser matter interactions.

Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility Electron-Positron-Proton Spectrometers (EPPSs). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement quality. The dispersion of low-energy electrons and positrons may be affected by fringe magnetic fields near the entrance of the EPPS.

A Millimeter-scale Single Charged Particle Dosimeter for Cancer Radiotherapy.

This paper presents a millimeter-scale CMOS 64×64 single charged particle radiation detector system for external beam cancer radiotherapy. A 1×1 m diode measures energy deposition by a single charged particle in the depletion region, and the array design provides a large detection area of 512×512 m. Instead of sensing the voltage drop caused by radiation, the proposed system measures the pulse width, i.

Assessment of DNA damage with an adapted independent reaction time approach implemented in Geant4-DNA for the simulation of diffusion-controlled reactions between radio-induced reactive species and a chromatin fiber.

Purpose: Simulation of indirect damage originating from the attack of free radical species produced by ionizing radiation on biological molecules based on the independent pair approximation is investigated in this work. In addition, a new approach, relying on the independent pair approximation that is at the origin of the independent reaction time (IRT) method, is proposed in the chemical stage of Geant4-DNA.

Methods: This new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method.

Independent reaction times method in Geant4-DNA: Implementation and performance.

Purpose: The simulation of individual particle tracks and the chemical stage following water radiolysis in biological tissue is an effective means of improving our knowledge of the physico-chemical contribution to the biological effect of ionizing radiation. However, the step-by-step simulation of the reaction kinetics of radiolytic species is the most time-consuming task in Monte Carlo track-structure simulations, with long simulation times that are an impediment to research. In this work, we present the implementation of the independent reaction times (IRT) method in Geant4-DNA Monte Carlo toolkit to improve the computational efficiency of calculating G-values, defined as the number of chemical species created or lost per 100 eV of deposited energy.

LET-Dependent Intertrack Yields in Proton Irradiation at Ultra-High Dose Rates Relevant for FLASH Therapy.

FLASH radiotherapy delivers a high dose (≥10 Gy) at a high rate (≥40 Gy/s). In this way, particles are delivered in pulses as short as a few nanoseconds. At that rate, intertrack reactions between chemical species produced within the same pulse may affect the heterogeneous chemistry stage of water radiolysis.

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio.

The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

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.

Monte Carlo track-structure for the radionuclide Copper-64: characterization of S-values, nanodosimetry and quantification of direct damage to DNA.

TOPAS-nBio was used to simulate, collision-to-collision, the complete trajectories of electrons in water generated during the explicit simulation of Cu decay. S-values and direct damage to the DNA were calculated representing the cell (C) and the cell nucleus (N) with concentric spheres of 5 μm and 4 μm in radius, respectively. The considered 'target'←'source' configurations, including the cell surface (Cs) and cytoplasm (Cy), were: C←C, C←Cs, N←N, N←Cy and N←Cs.