Review of chemical models and applications in Geant4-DNA: Report from the ESA BioRad III Project.

A chemistry module has been implemented in Geant4-DNA since Geant4 version 10.1 to simulate the radiolysis of water after irradiation. It has been used in a number of applications, including the calculation of G-values and early DNA damage, allowing the comparison with experimental data. Since the first version, numerous modifications have been made to the module to improve the computational efficiency and extend the simulation to homogeneous kinetics in bulk solution. With these new developments, new applications have been proposed and released as Geant4 examples, showing how to use chemical processes and models. This work reviews the models implemented and application developments for modeling water radiolysis in Geant4-DNA as reported in the ESA BioRad III Project.

The general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension to investigate mechanisms underlying the FLASH effect in radiotherapy: Current status and challenges.

FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown. One way to approach this problem is to gain insight into the initial parameters that can distinguish FLASH from conventional irradiation by simulating particle transport in aqueous media using the general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension. This review article discusses the current status of Geant4 and Geant4-DNA simulations to investigate mechanisms underlying the FLASH effect, as well as the challenges faced in this research field. One of the primary challenges is to accurately simulate the experimental irradiation parameters. Another challenge is the temporal extension of the simulations. This review also focuses on two hypotheses to explain the FLASH effect - namely the oxygen depletion hypothesis and the inter-track interactions hypothesis - and discusses how the Geant4 toolkit can be used to investigate them. The aim of this review is to provide an overview of Geant4 and Geant4-DNA simulations for FLASH radiotherapy and to highlight the challenges that need to be overcome in order to better study the FLASH effect.

Modeling of scavenging systems in water radiolysis with Geant4-DNA.

PURPOSE: This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of H2O2 following a 60Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons. METHODS: To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers. The first application area example required two computational steps to perform water radiolysis using NO2- and NO3- as scavengers and a 60Co irradiation. The oxygen depletion computation technique for the second application area example consisted of simulating track segments of 1 MeV electrons and determining the radio-induced loss and gain of oxygen molecules. RESULTS: The production of H2O2 under variable scavenging levels is consistent with the literature; the mean relative difference between the SBS and IRT methods is 7.2 % ± 0.5 %. For the oxygen depletion 1 µs post-irradiation, the mean relative difference between both methods is equal to 9.8 % ± 0.3 %. The results in the microsecond scale depend on the initial partial pressure of oxygen in water. In addition, the computed oxygen depletions agree well with the literature. CONCLUSIONS: The Geant4-DNA toolkit makes it possible to simulate water radiolysis in the presence of scavengers. This feature offers perspectives in radiobiology, with the possibility of simulating cell-relevant scavenging mechanisms.

Geant4-DNA Modeling of Water Radiolysis beyond the Microsecond: An On-Lattice Stochastic Approach.

In this work, we use the next sub-volume method (NSM) to investigate the possibility of using the compartment-based ("on-lattice") model to simulate water radiolysis. We, first, start with a brief description of the reaction-diffusion master equation (RDME) in a spatially discretized simulation volume ("mesh"), which is divided into sub-volumes (or "voxels"). We then discuss the choice of voxel size and merging technique of a given mesh, along with the evolution of the system using the hierarchical algorithm for the RDME ("hRDME"). Since the compartment-based model cannot describe high concentration species of early radiation-induced spurs, we propose a combination of the particle-based step-by-step ("SBS") Brownian dynamics model and the compartment-based model ("SBS-RDME model") for the simulation. We, finally, use the particle-based SBS Brownian dynamics model of Geant4-DNA as a reference to test the model implementation through several benchmarks. We find that the compartment-based model can efficiently simulate the system with a large number of species and for longer timescales, beyond the microsecond, with a reasonable computing time. Our aim in developing this model is to study the production and evolution of reactive oxygen species generated under irradiation with different dose rate conditions, such as in FLASH and conventional radiotherapy.