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Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed.
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Working Group (WG) 6 'Computational Dosimetry' of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications.
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Proteção Radiológica , Radiometria , Estudos Transversais , Método de Monte Carlo , Nêutrons , Doses de RadiaçãoRESUMO
Objective. The mechanisms of radiation-induced DNA damage can be understood via the fundamental acquisition of knowledge through a combination of experiments and modeling. Currently, most biological experiments are performed by irradiating an entire cell population, whereas modeling of radiation-induced effects is usually performed via Monte Carlo simulations with track structure codes coupled to realistic DNA geometries of a single-cell nucleus. However, the difference in scale between the two methods hinders a direct comparison because the dose distribution in the cell population is not necessarily uniform owing to the stochastic nature of the energy deposition. Thus, this study proposed the MINAS TIRITH tool to model the distribution of radiation-induced DNA damage in a cell population.Approach. The proposed method is based on precomputed databases of microdosimetric parameters and DNA damage distributions generated using the Geant4-DNA Monte Carlo Toolkit. First, a specific energyzwas assigned to each cell of an irradiated population for a particular absorbed doseDabs,following microdosimetric formalism. Then, each cell was assigned a realistic number of DNA damage events according to the specific energyz,respecting the stochastic character of its occurrence.Main results. This study validated the MINAS TIRITH tool by comparing its results with those obtained using the Geant4-DNA track structure code and a Geant4-DNA based simulation chain for DNA damage calculation. The different elements of comparison indicated consistency between MINAS TIRITH and the Monte Carlo simulation in case of the dose distribution in the population and the calculation of the amount of DNA damage.Significance. MINAS TIRITH is a new approach for the calculation of radiation-induced DNA damage at the cell population level that facilitates reasonable simulation times compared to those obtained with track structure codes. Moreover, this tool enables a more direct comparison between modeling and biological experimentation.
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Dano ao DNA , DNA , Simulação por Computador , DNA/química , Método de Monte CarloRESUMO
In the domains of medicine and space exploration, refining risk assessment models for protecting healthy tissue from ionizing radiation is crucial. Understanding radiation-induced effects requires biological experimentations at the cellular population level and the cellular scale modeling using Monte Carlo track structure codes. We present MINAS TIRITH, a tool using Geant4-DNA Monte Carlo-generated databases to study DNA damage distribution at the cell population scale. It introduces a DNA damage location module and proposes a method to convert double-strand breaks (DSB) into DNA Damage Response foci. We evaluate damage location precision and DSB-foci conversion parameters. MINAS TIRITH's accuracy is validated againstγ-H2AX foci distribution from cell population exposed to monoenergetic neutron beams (2.5 or 15.1 MeV) under different configurations, yielding mixed radiation fields. Strong agreement between simulation and experimental results was found demonstrating MINAS TIRITH's predictive precision in radiation-induced DNA damage topology. Additionally, modeling intercellular damage variability within a population subjected to a specific macroscopic dose identifies subpopulations, enhancing realistic fate models. This approach advances our understanding of radiation-induced effects on cellular systems for risk assessment improvement.
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Núcleo Celular , Dano ao DNA , Núcleo Celular/efeitos da radiação , Radiação Ionizante , Nêutrons , Método de Monte CarloRESUMO
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 by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after â¢OH + DNA and H⢠+ DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.
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Dano ao DNA , Dimetil Sulfóxido , Simulação por Computador , DNA/química , Método de Monte Carlo , Conformação de Ácido Nucleico , PlasmídeosRESUMO
Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed.
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Ouro , Nanopartículas Metálicas , Método de Monte Carlo , Radiografia , Dosagem Radioterapêutica , Incerteza , Raios XRESUMO
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. The evaluation of Geant4-DNA was accomplished with TOPAS-nBio. For that, we compared predicted time-dependentGvalues in pure liquid water for·OH, e-aq, and H2with published experimental data. For H2O2and H·, simulation of added scavengers at different concentrations resulted in better agreement with measurements. In addition, DNA geometry information was integrated with chemistry simulation in TOPAS-nBio to realize reactions between radiolytic chemical species and DNA. This was used in the estimation of the yield of single-strand breaks (SSB) induced by137Csγ-ray radiolysis of supercoiled pUC18 plasmids dissolved in aerated solutions containing DMSO. The efficiency of SSB induction by reaction between radiolytic species and DNA used in the simulation was chosen to provide the best agreement with published measurements. An RMS displacement of 1.24 nm provided agreement with measured data within experimental uncertainties for time-dependentGvalues and under the presence of scavengers. SSB efficiencies of 24% and 0.5% for·OH and H·, respectively, led to an overall agreement of TOPAS-nBio results within experimental uncertainties. The efficiencies obtained agreed with values obtained with published non-homogeneous kinetic model and step-by-step Monte Carlo simulations but disagreed by 12% with published direct measurements. Improvement of the spatial resolution of the DNA damage model might mitigate such disagreement. In conclusion, with these improvements, Geant4-DNA/TOPAS-nBio provides a fast, accurate, and user-friendly tool for simulating DNA damage under low linear energy transfer irradiation.
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Dano ao DNA , Água , Simulação por Computador , Transferência Linear de Energia , Método de Monte CarloRESUMO
PURPOSE: The GEANT4 general-purpose Monte Carlo simulation toolkit is able to simulate physical interaction processes of electrons, hydrogen and helium atoms with charge states (H0, H+) and (He0, He+, He2+), respectively, in liquid water, the main component of biological systems, down to the electron volt regime and the submicrometer scale, providing GEANT4 users with the so-called "GEANT4-DNA" physics models suitable for microdosimetry simulation applications. The corresponding software has been recently re-engineered in order to provide GEANT4 users with a coherent and unique approach to the simulation of electromagnetic interactions within the GEANT4 toolkit framework (since GEANT4 version 9.3 beta). This work presents a quantitative comparison of these physics models with a collection of experimental data in water collected from the literature. METHODS: An evaluation of the closeness between the total and differential cross section models available in the GEANT4 toolkit for microdosimetry and experimental reference data is performed using a dedicated statistical toolkit that includes the Kolmogorov-Smirnov statistical test. The authors used experimental data acquired in water vapor as direct measurements in the liquid phase are not yet available in the literature. Comparisons with several recommendations are also presented. RESULTS: The authors have assessed the compatibility of experimental data with GEANT4 microdosimetry models by means of quantitative methods. The results show that microdosimetric measurements in liquid water are necessary to assess quantitatively the validity of the software implementation for the liquid water phase. Nevertheless, a comparison with existing experimental data in water vapor provides a qualitative appreciation of the plausibility of the simulation models. The existing reference data themselves should undergo a critical interpretation and selection, as some of the series exhibit significant deviations from each other. CONCLUSIONS: The GEANT4-DNA physics models available in the GEANT4 toolkit have been compared in this article to available experimental data in the water vapor phase as well as to several published recommendations on the mass stopping power. These models represent a first step in the extension of the GEANT4 Monte Carlo toolkit to the simulation of biological effects of ionizing radiation.
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Modelos Teóricos , Água , Dano ao DNA , Elasticidade , Elétrons , Hélio , Método de Monte Carlo , Prótons , Radiometria , Espalhamento de Radiação , SoftwareRESUMO
The decision to irradiate during pregnancy is based on a risk benefit compromise of two kinds: maternal risk and fetal risk. The aim of this work is to determine the foetal risk, and uterine dose measurement in proton therapy. Foetal exposure during treatment is linked to two sources: the treatment phase, and the repositioning phase. An Alderson-Rando anthropomorphic ghost (170cm, 74kg) was positioned on the table in the treatment position. A tissue-equivalent proportional counter (TEPC), adapted to the analysis of complex radiation fields (neutron and photonics), was used to determine the irradiation related to the treatment phase. An AT1123 radiation survey meter was used to measure photons generated by X-ray radiation. I dosimetry was proposed using radio-photoluminescent dosimeters, allowing for a daily check of the dose received in the uterus. The treatment phase produces higher uterine doses than the positioning phase, but these remain very low. The equivalent dose received in the uterus for the entire treatment is estimated at 840 µSv. Using a methodology for measuring the out-of-field dose with pencil beam scanning proton therapy, the foetal dose in the first trimester was well below the acceptance dose of 100 mGy determined by the International Commission on Radiological Protection.
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Feto/efeitos da radiação , Posicionamento do Paciente/efeitos adversos , Complicações Neoplásicas na Gravidez/radioterapia , Exposição à Radiação , Útero/efeitos da radiação , Adulto , Feminino , Cabeça/efeitos da radiação , Humanos , Nêutrons , Posicionamento do Paciente/métodos , Imagens de Fantasmas , Fótons , Gravidez , Primeiro Trimestre da GravidezRESUMO
PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.
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Ouro/química , Nanopartículas Metálicas/química , Radioterapia/métodos , Animais , Simulação por Computador , Elétrons , Humanos , Imageamento Tridimensional , Técnicas In Vitro , Camundongos , Método de Monte Carlo , Neoplasias/diagnóstico por imagem , Controle de Qualidade , Radiometria , Reprodutibilidade dos Testes , Água , Raios XRESUMO
Ionizing radiation is a peculiar perturbation when it comes to damage to biological systems: it proceeds through discrete energy depositions, over a short temporal scale and a spatial scale critical for subcellular targets as DNA, whose damage complexity determines the outcome of the exposure. This lies at the basis of the success of track structure (and nanodosimetry) and microdosimetry in radiation biology. However, such reductionist approaches cannot account for the complex network of interactions regulating the overall response of the system to radiation, particularly when effects are manifest at the supracellular level and involve long times. Systems radiation biology is increasingly gaining ground, but the gap between reductionist and holistic approaches is becoming larger. This paper presents considerations on what roles track structure and microdosimetry can have in the attempt to fill this gap, and on how they can be further exploited to interpret radiobiological data and inform systemic approaches.
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Radiobiologia , Radiometria/métodos , Biologia de Sistemas , Dano ao DNA/efeitos da radiação , Doses de Radiação , Radiação Ionizante , Eficiência Biológica RelativaRESUMO
PURPOSE: In this work, we present simulated double-strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi-scale description of the DNA target from the molecular level to the whole human genome representation. METHODS: The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4-DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. RESULTS: More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. CONCLUSIONS: The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes.
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Núcleo Celular/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Heterocromatina , Método de Monte Carlo , Radiação Ionizante , Núcleo Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Eucromatina , Células Endoteliais da Veia Umbilical Humana , HumanosRESUMO
Within EURADOS Working Group 6 'Computational Dosimetry', the micro and nanodosimetry task group 6.2 has recently conducted a Monte Carlo (MC) exercise open to participants around the world. The aim of this exercise is to quantify the contribution to the uncertainty of micro and nanodosimetric simulation results arising from the use of different electron-impact cross-sections, and hence physical models, employed by different MC codes (GEANT4-DNA, PENELOPE, MCNP6, FLUKA, NASIC and PHITS). Comparison of the participants' simulation results for both micro and nanodosimetric quantities using different MC codes was the first step of the exercise. The deviation between results is due to different cross-sections but also different tracking methods and particle transport cut-off energies. The second step of the exercise will involve using identical cross-section datasets to account only for the other variations in the first step, thus enabling the determination of the uncertainty contribution due to different cross-sections. This paper presents a comparison of the MC simulation results obtained in the first part of the exercise. For the microdosimetric simulations, particularly in the configuration where the electron source is contained within the micrometric target, the choice of MC code has a small influence on the results. For the nanodosimetric results, on the other hand, the mean ionisation cluster size distribution (ICSD) was sensitive to the physical models used in the MC codes. The ICSD was therefore chosen to study the influence of different cross-section data on the uncertainty of simulation results.
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Método de Monte Carlo , Radiometria/métodos , Incerteza , Simulação por Computador , Elétrons , Europa (Continente) , Radioisótopos do Iodo , Modelos Estatísticos , Modelos Teóricos , SoftwareRESUMO
Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.
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Dano ao DNA , Simulação por Computador , Reparo do DNA , Transferência Linear de Energia , Modelos Teóricos , Método de Monte CarloRESUMO
This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path ). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.
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In 2011, the International Commission on Radiological Protection (ICRP) reviewed its recommendation concerning the equivalent dose limit for the eye lens, lowering it to 20 mSv in a year, for occupational exposure in planned exposure situations. The ICRP's statement does not contain any explicit recommendations regarding the organ dose limit for the eye lens for public exposure. For the moment, no change is proposed. But, to be coherent in the overall approach, the current equivalent limit for the public might be lowered. A similar yardstick than in the former recommendation may be used, that is to say a reduction of 10 times lower than that for occupational exposure. In this context, additional data on potential scenarios for public exposure of the eye lens are necessary. This paper, mainly based on a literature study, aims to provide, as far as possible, an exhaustive list of the situations in which members of the public can be exposed at the level of the eye lens. Once these situations have been defined, some calculations, made to assess the associated doses to the eye lens, are presented. This literature study did not reveal any current situations where members of the public would receive significant radiation doses to the eye lens. Indeed, the situations in which the dose to the eye lens might reach around 1 mSv per year for the public are extremely rare.
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Exposição Ambiental/efeitos adversos , Cristalino/efeitos da radiação , Materiais de Construção , Materiais Dentários , Humanos , Cooperação Internacional , Joias , Lentes , Exposição Ocupacional , Lesões por Radiação/prevenção & controle , Proteção Radiológica/métodos , Radiometria , Medição de Risco , Televisão , Trítio/análise , ArmasRESUMO
The high-energy programme of the HINDAS European project has provided a large amount of experimental data and led to a better understanding of the spallation reaction mechanism and the development of more reliable spallation models. These data, or the new models, which have been implemented into high-energy transport codes, can be now used to predict with a larger confidence or, at least with a known uncertainty, some important quantities for the design of spallation sources. In this paper, examples concerning the residue production in a Pb-Bi target and the high-energy neutrons escaping the target are presented. In the first case, the activity and the amount of radioactive volatile elements that can be released, in case of a containment failure, are calculated and the level of confidence of the calculation is assessed. The second example shows that the models correctly predict the high-energy tail of the neutron spectrum, which is important for radioprotection in the facility.
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Algoritmos , Monitoramento de Radiação/métodos , Proteção Radiológica/métodos , Radioisótopos/análise , Software , Desenho de Equipamento/métodos , Nêutrons , Doses de Radiação , Medição de Risco/métodos , Fatores de RiscoRESUMO
This article presents the results of the simulated irradiation with protons and alpha particles of two different geometrical models, representing a cell nucleus and its chromatin content. The characteristics of the energy deposition are studied at both micrometric and nanometric length scales. In particular, the stochastic distributions of the quantities associated with the total energy deposit in the micrometric volume are derived and compared with the physical characteristics of the clusters of energy deposits. An innovative multi-scale correlation method is introduced and tested against the simulations' data. This new approach links the two relevant length scales exploiting the differences in the kinetic energy spectra of the secondary electrons produced by the primary particles. The characteristics of the energy deposition of the electrons in the chosen material are determined in the first instance. Few free parameters of the model, linking the electrons energy deposits with the total energy deposit of the primary particles, can be used for summarising the characteristic of the irradiation with the chosen radiation quality at the two different length scales.
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Partículas alfa , Simulação por Computador , Prótons , Exposição à Radiação/análise , Núcleo Celular , Cromatina , Elétrons , Humanos , Transferência Linear de EnergiaRESUMO
The aim of this study was to evaluate the influence of the geometrical detail of the DNA on nanodosimetric parameters of track structure induced by protons and alpha particles of different energies (LET values ranging from 1 to 162.5 keV µm-1) as calculated by Geant4-DNA Monte Carlo simulations.The first geometry considered consisted of a well-structured placement of a realistic description of the DNA double helix wrapped around cylindrical histones (GeomHist) forming a 18 kbp-long chromatin fiber. In the second geometry considered, the DNA was modeled as a total of 1800 ten bp-long homogeneous cylinders (2.3 nm diameter and 3.4 nm height) placed in random positions and orientations (GeomCyl). As for GeomHist, GeomCyl contained a DNA material equivalent to 18 kbp. Geant4-DNA track structure simulations were performed and ionizations were counted in the scoring volumes. For GeomCyl, clusters were defined as the number of ionizations (ν) scored in each 10 bp-long cylinder. For GeomHist, clusters of ionizations scored in the sugar-phosphate groups of the double-helix were revealed by the DBSCAN clustering algorithm according to a proximity criteria among ionizations separated by less than 10 bp. The topology of the ionization clusters formed using GeomHist and GeomCyl geometries were compared in terms of biologically relevant nanodosimetric quantities.The discontinuous modeling of the DNA for GeomCyl led to smaller cluster sizes than for GeomHist. The continuous modeling of the DNA molecule for GeomHist allowed the merging of ionization points by the DBSCAN algorithm giving rise to larger clusters, which were not detectable within the GeomCyl geometry. Mean cluster size (m1) was found to be of the order of 10% higher for GeomHist compared to GeomCyl for LET < 15 keV µm-1. For higher LETs, the difference increased with LET similarly for protons and alpha particles. Both geometries showed the same relationship between m1 and the cumulative relative frequency of clusters with v≥3 (f3) within statistical variations, independently of particle type. In order to obtain ionization cluster size distributions relevant for biological DNA lesions, the complex DNA geometry and a scoring method without fixed boundaries should be preferred to the simple cylindrical geometry with a fixed scoring volume.
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DNA/química , Prótons , Doses de Radiação , Partículas alfa , Simulação por Computador , DNA/efeitos da radiação , Dano ao DNA , Método de Monte CarloRESUMO
The research project BioQuaRT within the European Metrology Research Programme aimed at correlating ion track structure characteristics with the biological effects of radiation and developed measurement and simulation techniques for determining ion track structure on different length scales from about 2 nm to about 10 µm. Within this framework, we investigated methods to translate track-structure quantities derived on a nanometre scale to macroscopic dimensions. Here we make use of parameterizations that link the energy of the projectile to the ionization pattern of the track using nanodosimetric ionization cluster size distributions. They were defined with data generated by simulations of ion tracks in liquid water using the Geant4 Monte Carlo toolkit with the Geant4-DNA processes. For the clinical situation with a mixed radiation field, where particles of various energies hit a cell from several directions, we have to find macroscopic relevant mean values. They can be determined by appropriate local weighting functions for the identified parameterization. We show that a stopping power weighted mean value of the mentioned track structure properties can describe the overall track structure in a cell exposed to a mixed radiation field. The parameterization, together with the presented stopping power weighting approach, show how nanometric track structure properties could be integrated into treatment planning systems without the need to perform time consuming simulations on the nanometer level for each individual patient.