Extension de l'outil Monte Carlo généraliste Geant4 pour la simulation de la radiolyse de l'eau dans le cadre du projet Geant4-DNA

Ce travail, réalisé dans le cadre du projet Geant4-DNA, consiste à concevoir un prototype pour la simulation des effets chimiques précoces des rayonnements ionisants. Le modèle de simulation étudié repose sur la représentation particule-continuum où toutes les molécules sont explicitement simulées et où le solvant est traité comme un continuum. La méthode proposée par cette thèse a pour but d'améliorer les performances de ce type de simulation. Elle se base sur (1) la combinaison d'une méthode de pas en temps dynamiques avec un processus de pont Brownien pour la prise en compte des réactions chimiques et afin d'éviter une simulation à pas en temps fixe, coûteuse en temps de calcul, et (2) sur la structure de données k-d tree pour la recherche du voisin le plus proche permettant, pour une molécule donnée, une localisation rapide du réactif le plus proche. La précision de l'algorithme est démontrée par la comparaison des rendements radiochimiques en fonction du temps et en fonction du transfert d'énergie linéaire avec des résultats d'autres codes Monte-Carlo et des données expérimentales. A partir de ce prototype, une tentative de prédiction du nombre et du type d'interactions radicaux-ADN a été entreprise basée sur d'une description simplifiée du noyau cellulaire.The purpose of this work, performed under the Geant4-DNA project, is to design a prototype for simulating early chemical effects of ionizing radiation. The studied simulation model is based on the particle-continuum representation where all the molecules are explicitly simulated, and where the solvent is treated as a continuum. The method proposed by this thesis aims at improving the performance of this type of simulation. It is based on (1) a dynamical time steps method with a Brownian bridge process, to account for chemical reactions, which avoids the costly fixed time-step simulations, and (2) on the k-d tree data structure for quickly locating, for a given molecule, its closest reactants. The accuracy of the algorithm is demonstrated by comparing radiochemical yields over time and depending on the linear energy transfer with results obtained from other Monte Carlo codes and experimental data. Using this prototype, an attempt to predict the number and type of radical attacks on DNA has been performed using a simplified description of the cell nucleus

Extension de l'outil Monte Carlo généraliste Geant4 pour la simulation de la radiolyse de l'eau dans le cadre du projet Geant4-DNA

Ce travail, réalisé dans le cadre du projet Geant4-DNA, consiste à concevoir un prototype pour la simulation des effets chimiques précoces des rayonnements ionisants. Le modèle de simulation étudié repose sur la représentation particule-continuum où toutes les molécules sont explicitement simulées et où le solvant est traité comme un continuum. La méthode proposée par cette thèse a pour but d'améliorer les performances de ce type de simulation. Elle se base sur (1) la combinaison d'une méthode de pas en temps dynamiques avec un processus de pont Brownien pour la prise en compte des réactions chimiques et afin d'éviter une simulation à pas en temps fixe, coûteuse en temps de calcul, et (2) sur la structure de données k-d tree pour la recherche du voisin le plus proche permettant, pour une molécule donnée, une localisation rapide du réactif le plus proche. La précision de l'algorithme est démontrée par la comparaison des rendements radiochimiques en fonction du temps et en fonction du transfert d'énergie linéaire avec des résultats d'autres codes Monte-Carlo et des données expérimentales. A partir de ce prototype, une tentative de prédiction du nombre et du type d'interactions radicaux-ADN a été entreprise basée sur d'une description simplifiée du noyau cellulaire.The purpose of this work, performed under the Geant4-DNA project, is to design a prototype for simulating early chemical effects of ionizing radiation. The studied simulation model is based on the particle-continuum representation where all the molecules are explicitly simulated, and where the solvent is treated as a continuum. The method proposed by this thesis aims at improving the performance of this type of simulation. It is based on (1) a dynamical time steps method with a Brownian bridge process, to account for chemical reactions, which avoids the costly fixed time-step simulations, and (2) on the k-d tree data structure for quickly locating, for a given molecule, its closest reactants. The accuracy of the algorithm is demonstrated by comparing radiochemical yields over time and depending on the linear energy transfer with results obtained from other Monte Carlo codes and experimental data. Using this prototype, an attempt to predict the number and type of radical attacks on DNA has been performed using a simplified description of the cell nucleus

Mechanistic DNA damage simulations in Geant4-DNA Part 2: Electron and proton damage in a bacterial cell

We extended a generic Geant4 application for mechanistic DNA damage simulations to an Escherichia coli cell geometry, finding electron damage yields and proton damage yields largely in line with experimental results. Depending on the simulation of radical scavenging, electrons double strand breaks (DSBs) yields range from 0.004 to 0.010 DSB Gy-1 Mbp-1, while protons have yields ranging from 0.004 DSB Gy-1 Mbp-1 at low LETs and with strict assumptions concerning scavenging, up to 0.020 DSB Gy-1 Mbp-1 at high LETs and when scavenging is weakest. Mechanistic DNA damage simulations can provide important limits on the extent to which physical processes can impact biology in low background experiments. We demonstrate the utility of these studies for low dose radiation biology calculating that in E. coli, the median rate at which the radiation background induces double strand breaks is 2.8 × 10-8 DSB day-1, significantly less than the mutation rate per generation measured in E. coli, which is on the order of 10-3

Mechanistic DNA damage simulations in Geant4-DNA part 1: A parameter study in a simplified geometry

Mechanistic modelling of DNA damage in Monte Carlo simulations is highly sensitive to the parameters that define DNA damage. In this work, we use a simple testing geometry to investigate how different choices of physics models and damage model parameters can change the estimation of DNA damage in a mechanistic DNA damage simulation built in Geant4-DNA. The choice of physics model can lead to variations by up to a factor of two in the yield of physically induced strand breaks, and the parameters that determine scavenging, and physical and chemical single strand break induction can have even larger consequences. Using low energy electrons as primary particles, a variety of parameters are tested in this geometry in order to arrive at a parameter set consistent with past simulation studies. We find that the modelling of scavenging can play an important role in determining results, and speculate that high-scavenging regimes, where only chemical radicals within 1 nm of DNA are simulated, could provide a good means of testing mechanistic DNA simulation

Geant4 visualization: pBR322 plasmid DNA molecule irradiation by 20 MeV proton in liquid water

<p><strong>Geant4 simulation of pBR322 plasmid DNA irradiation by 20 MeV proton particle in liquid water.</strong></p> <p>Computer visualization of plasmid DNA irradiation in liquid water as modelled by the Geant4 Monte Carlo track structure code.</p> <p>pBR322 plasmid DNA geometry created using A. Vologodskii's group (see Huang, J., Schlick, T. and Vologodskii, T. (2001) Dynamics of site juxtaposition in supercoiled DNA. Proc. Natl. Acad. Sci. USA, 98, 968-973) was included in a Geant4-DNA physical and chemical stage simulation of liquid water sphere irradiation by a 20 MeV proton track.</p> <p>First the physical stage of radiation action is modelled; proton track is shown in green, yellow dots correspond to interaction events. Secondaries are followed down to thermalization.</p> <p>Next, the chemical stage simulation for first 100 ns is visualized. Individual chemical species diffusing in space and reacting with each other are shown as colour trails, the color codes chemical species type.</p> <p>Visualization combines the plasmid DNA geometry interface to A. Vologodskii's group code written by Václav Štěpán and the chem3 Geant4 example by M. Karamitros, S. Meylan, Y. Perrot and V. Štěpán.</p> <p>For more information about water radiolysis and chemical stage modelling using Geant4, please see  "Diffusion-controlled reactions modeling in Geant4-DNA" by M. Karamitros et al., doi:10.1016/j.jcp.2014.06.011</p

Geant4-DNA visualization: Evolution of 1 keV electron track in liquid water in space and time

<p>Geant4-DNA generated track of 1 keV electron, followed up to 100 ns during chemical stage.<br>Using pre-release Geant4 10.1 code.</p> <p>First, the physical stage of radiation action is modeled, using Geant4-DNA physics. 1 keV electron track is fully slowed down and thermalized in a 150 nm sphere of liquid water.</p> <p>Yellow points correspond to interaction events in liquid water.</p> <p>Next, the chemical stage simulation for first 100 ns is visualized. Individual radical species diffusing in space and reacting with each other are shown as colour trails, the color coding chemical species type.</p> <p>References:</p> <p>Geant4 10.0, patch 01, Geant4 DNA chemistry code e964ead.<br>Code using the chem3 example by M. Karamitros, S. Meylan, Y. Perrot and V. Štěpán, video rendered by V. Štěpán on March 31, 2014.</p> <p>Internal ref: chem3-100ns-1kev-e</p> <p> </p

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.

PurposeSimulation 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.MethodsThis new approach has been designed to respect the current Geant4-DNA chemistry framework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make it more convenient for biological damage simulations. Estimates of the evolution of free species as well as biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for the dynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, and this newly implemented IRT.ResultsResults show a gain in computation time of a factor of 30 for high LET particle tracks with a better than 10% agreement on the number of DNA hits between the value obtained with the IRT method as implemented in this work and the SBS method currently available in Geant4-DNA.ConclusionOffering in Geant4-DNA more efficient methods for the chemical step based on the IRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in this paper

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 producedby 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 isat the origin of the independent reaction time (IRT) method, is proposed in the chemical stage ofGeant4-DNA.Methods: This new approach has been designed to respect the current Geant4-DNA chemistryframework while proposing a variant IRT method. Based on the synchronous algorithm, this implementation allows us to access the information concerning the position of radicals and may make itmore convenient for biological damage simulations. Estimates of the evolution of free species as wellas biological hits in a segment of DNA chromatin fiber in Geant4-DNA were compared for thedynamic time step approach of the step-by-step (SBS) method, currently used in Geant4-DNA, andthis newly implemented IRT.Results: Results show a gain in computation time of a factor of 30 for high LET particle tracks witha better than 10% agreement on the number of DNA hits between the value obtained with the IRTmethod as implemented in this work and the SBS method currently available in Geant4-DNA.Conclusion: Offering in Geant4-DNA more efficient methods for the chemical step based on theIRT method is a task in progress. For the calculation of biological damage, information on the position of chemical species is a crucial point. This can be achieved using the method presented in thispape

Independent reaction times method in Geant4‐DNA: Implementation and performance

PurposeThe 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&nbsp;eV of deposited energy.MethodsThe computational efficiency of IRT, as implemented, is compared to that from available Geant4-DNA step-by-step simulations for electrons, protons and alpha particles covering a wide range of linear energy transfer (LET). The accuracy of both methods is verified using published measured data from fast electron irradiations for • OH and eaq- for time-dependent G-values. For IRT, simulations in the presence of scavengers irradiated by cobalt-60 γ-ray and 2&nbsp;MeV protons are compared with measured data for different scavenging capacities. In addition, a qualitative assessment comparing measured LET-dependent G-values with Geant4-DNA calculations in pure liquid water is presented.ResultsThe IRT improved the computational efficiency by three orders of magnitude relative to the step-by-step method while differences in G-values by 3.9% at 1&nbsp;μs were found. At 7&nbsp;ps, • OH and eaq- yields calculated with IRT differed from recent published measured data by 5%&nbsp;±&nbsp;4% and 2%&nbsp;±&nbsp;4%, respectively. At 1&nbsp;μs, differences were 9%&nbsp;±&nbsp;5% and 6%&nbsp;±&nbsp;7% for • OH and eaq- , respectively. Uncertainties are one standard deviation. Finally, G-values at different scavenging capacities and LET-dependent G-values reproduced the behavior of measurements for all radiation qualities.ConclusionThe comprehensive validation of the Geant4-DNA capabilities to accurately simulate the chemistry following water radiolysis is an ongoing work. The implementation presented in this work is a necessary step to facilitate performing such a task