Effect of FLASH dose-rate and oxygen concentration in the production of HOin cellular-like media versus water: a Monte Carlo track-structure study.

To study the effect of dose-rate in the time evolution of chemical yields produced in pure water versus a cellular-like environment for FLASH radiotherapy research. A version of TOPAS-nBio with Tau-Leaping algorithm was used to simulate the homogenous chemistry stage of water radiolysis using three chemical models: 1) liquid water model that considered scavenging of eaq-, H● by dissolved oxygen; 2) Michaels & Hunt model that considered scavenging of ●OH, eaq-, and H● by biomolecules existing in cellular environment; 3) Wardman model that considered model 2) and the chemical repair enzyme glutathione (GHS). H2O2 concentrations at conventional and FLASH dose-rates were compared with published measurements.

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.

Tumor growth and vascular redistribution contributes to the dosimetric preferential effect of microbeam radiotherapy: a Monte Carlo study.

The radiobiological mechanisms behind the favorable response of tissues to microbeam radiation therapy (MRT) are not fully described yet. Among other factors, the differential action to tumor and normal tissue vasculature is considered to contribute to MRT efficacy. This computational study evaluates the relevance of tumor growth stage and associated vascular redistribution to this effect.

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.

A clustering tool for generating biological geometries for computational modeling in radiobiology.

To develop a computational tool that converts biological images into geometries compatible with computational software dedicated to the Monte Carlo simulation of radiation transport (TOPAS), and subsequent biological tissue responses (CompuCell3D). The depiction of individual biological entities from segmentation images is essential in computational radiobiological modeling for two reasons: image pixels or voxels representing a biological structure, like a cell, should behave as a single entity when simulating biological processes, and the action of radiation in tissues is described by the association of biological endpoints to physical quantities, as radiation dose, scored the entire group of voxels assembling a cell.The tool is capable of cropping and resizing the images and performing clustering of image voxels to create independent entities (clusters) by assigning a unique identifier to these voxels conforming to the same cluster.

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.

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.

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.

Cellular lethal damage of Cu incorporated in mammalian genome evaluated with Monte Carlo methods.

Purpose: Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations.

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)..

GEANT4-DNA simulation of temperature-dependent and pH-dependent yields of chemical radiolytic species.

GEANT4-DNA can simulate radiation chemical yield (-value) for radiolytic species such as the hydrated electron (eaq-) with the independent reaction times (IRT) method, however, only at room temperature and neutral pH. This work aims to modify the GEANT4-DNA source code to enable the calculation of-values for radiolytic species at different temperatures and pH values.In the GEANT4-DNA source code, values of chemical parameters such as reaction rate constant, diffusion coefficient, Onsager radius, and water density were replaced by corresponding temperature-dependent polynomials.

Microdosimetric Analysis for Boron Neutron Capture Therapy via Monte Carlo Track Structure Simulation with Modified Lithium Cross-sections.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio.

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..

Dosimetric characterization of single- and dual-port temporary tissue expanders for postmastectomy radiotherapy using Monte Carlo methods.

Purpose: The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE.

Methods: The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1).

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.

Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA.

Purpose: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology.

Methods: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs.

Development of Ultra-High Dose-Rate (FLASH) Particle Therapy.

Research efforts in FLASH radiotherapy have increased at an accelerated pace recently. FLASH radiotherapy involves ultra-high dose rates and has shown to reduce toxicity to normal tissue while maintaining tumor response in pre-clinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies performed to-date with proton, electron, and heavy ion FLASH radiotherapy, with particular emphasis on the physical aspects of each study and the advantages and disadvantages of each modality.

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.

The relation between microdosimetry and induction of direct damage to DNA by alpha particles.

In radiopharmaceutical treatments-particles are employed to treat tumor cells. However, the mechanism that drives the biological effect induced is not well known. Being ionizing radiation,-particles can affect biological organisms by producing damage to the DNA, either directly or indirectly.

Geant4-DNA simulation of the pre-chemical stage of water radiolysis and its impact on initial radiochemical yields.

This paper demonstrates the impact of the pre-chemical stage, especially the dissociation scheme and the associated probabilities, on water radiolysis simulation using the Geant4-DNA Monte Carlo track structure simulation toolkit. The models and parameters provided by TRACs have been collected and implemented into Geant4-DNA. In order to evaluate their influence on water radiolysis simulation, the radiochemical yields (G-values) are evaluated as a function of time and LET using the "chem6" Geant4-DNA example, and they are compared with published experimental and calculated data.