Microdosimetry of electrons in liquid water using the low-energy models of Geant4

The biological effects of ionizing radiation at the cellular level are frequently studied using the well-known formalism of microdosimetry, which provides a quantitative description of the stochastic aspects of energy deposition in irradiated media. Energy deposition can be simulated using Monte Carlo codes, some adopting a computationally efficient condensed-history approach, while others follow a more detailed track-structure approach. In this work, we present the simulation of microdosimetry spectra and related quantities (frequency-mean and dose-mean lineal energies) for incident monoenergetic electrons (50 eV-10 keV) in spheres of liquid water with dimensions comparable to the size of biological targets: base pairs (2 nm diameter), nucleosomes (10 nm), chromatin fibres (30 nm) and chromosomes (300 nm). Simulations are performed using the condensed-history low-energy physics models ( Livermore and Penelope ) and the track-structure Geant4-DNA physics models, available in the Geant4 Monte Carlo simulation toolkit. The spectra are compared and the influence of simulation parameters and different physics models, with emphasis on recent developments, is discussed, underlining the suitability of Geant4-DNA models for microdosimetry simulations. It is further shown that with an appropriate choice of simulation parameters, condensed-history transport may yield reasonable results for sphere sizes as small as a few tens of a nanometer

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources

Simulation of DNA damage using the “molecularDNA” example application of Geant4-DNA

The scientific community has a large interest in the studies of DNA damage and response after exposure to ionizing radiation. Several in-silico methods have been proposed so far to model and study the mechanisms of DNA damage using Monte Carlo simulations. The “molecularDNA” example is one of the most recent applications to simulate the irradiation of human cancer cells and bacteria using Geant4-DNA. This example enables the simulation of the physical, physico-chemical and chemical stages of liquid water irradiation, including radiolytic processes following the particle irradiation of the pre-defined human cell geometries and it can be used to calculate the early direct and non-direct DNA damage such as single (SSB) and double strand breaks (DSB) as well as DNA fragment distribution. The application is user friendly and can be used following simple macro commands. The results of the Monte Carlo simulation are compared to experimental data of DSB yields, as well as with previously published simulation data.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, September 28-29, 2023; Kragujeva

Simulation of DNA damage using Geant4-DNA: an overview of the “molecularDNA” example application

Purpose The scientific community shows great interest in the study of DNA damage induction, DNA damage repair, and the biological effects on cells and cellular systems after exposure to ionizing radiation. Several in silico methods have been proposed so far to study these mechanisms using Monte Carlo simulations. This study outlines a Geant4-DNA example application, named “molecularDNA”, publicly released in the 11.1 version of Geant4 (December 2022). Methods It was developed for novice Geant4 users and requires only a basic understanding of scripting languages to get started. The example includes two different DNA-scale geometries of biological targets, namely “cylinders” and “human cell”. This public version is based on a previous prototype and includes new features, such as: the adoption of a new approach for the modeling of the chemical stage, the use of the standard DNA damage format to describe radiation-induced DNA damage, and upgraded computational tools to estimate DNA damage response. Results Simulation data in terms of single-strand break and double-strand break yields were produced using each of the available geometries. The results were compared with the literature, to validate the example, producing less than 5% difference in all cases. Conclusion: “molecularDNA” is a prototype tool that can be applied in a wide variety of radiobiology studies, providing the scientific community with an open-access base for DNA damage quantification calculations. New DNA and cell geometries for the “molecularDNA” example will be included in future versions of Geant4-DNA

Monte Carlo models of electron transport for dose-enhancement calculations in nanoparticle-aided radiotherapy

International audienc

Interaction of radiation with matter

Written for students approaching the subject for the first time, this text provides a solid grounding in the physics of the interactions of photons and particles with matter, which is the basis of radiological physics and radiation dosimetry. The authors first present the relevant atomic physics and then describe the interactions, emphasizing practical applications in health/medical physics and radiation biology. They cover such important topics as microdosimetry, interaction of photons with matter, electron energy loss, and dielectric response. Each chapter includes exercises and a summary.Section IIntroductionRadiation Transport CodesBasic Knowledge of RadiationDefinitions of RadiationElectron VoltSpecial Theory of RelativityElectromagnetic Wave and PhotonInteraction Cross SectionsQuantities and Units of RadiationAtomsAtomic Nature of MatterRutherford's Atomic ModelBohr's Quantum TheoryQuantum MechanicsAtomic StructureAtomic NucleusConstituents of NucleusBinding Energy of NucleusNuclear ModelsNuclear ReactionNuclear FissionNuclear FusionRadioactivityTypes of RadioactivityFormulas of Radioactive DecayX-RaysGeneration of X-RaysContinuous X-RaysCharacteristic X-RaysAuger Electron

Collagen fibril diameter in relation to bone site. A quantitative ultrastructural study. Micron 36:703–705

The collagen fibril diameter was measured in cortical bone samples from the femoral neck, rear and front tibia of female and male rats and rabbits using electron microscopy analysis. In most cases, statistically significant differences in mean fibril diameter values between different bone sites were detected. The order of magnitude for the above structural parameter was the same for both genders in both experimental species. In rats, the greatest mean diameter value was that for the femoral, while in rabbits, the one for the rear tibia demonstrating a dependence on bone use and life style. An important aspect was the agreement between these observations and the mean values for Ca/P ratio, as observed in previous experiments, in the same bone sites and animals. Collagen fibril diameter and Ca/P ratio can both serve as indexes of bone quality. KEYWORDS: collagen fibrils, diameter, electron microscopy, cortical bone, calcium/phosphorus ratio INTRODUCTION In bone, collagen represents more than 90% of the organic bone matrix. It confers resistance to the structure and establishes the biomechanical properties of the tissue Regarding the bone mineral content, it is generally accepted that its measurement is an appropriate estimate of bone strength. Changes in the amounts of Ca and P in biological apatites do not go hand in hand; therefore, a decrease in bone density may be due to a decrease in either Ca or P, or to dissimilar decreases in both. Consequently, the determination of the Ca/P ratio may provide a sensitive measure of bone mineral changes and may add to our understanding of the changes occurring in bone diseases. It is known that the mechanical strength of bone depends, first of all, on the condition of the cortical bone 1110 1. Compare the mean collagen fibril diameter values between bone sites, genders, and animal species 2. Use the collagen fibril diameter as step towards understanding its importance as an indicator of bone strength 3. Compare the mean collagen fibril diameter values with the previously obtained MATERIALS AND METHODS Animals -Bone Samples Female and male Wistar rats and rabbits, 18 and 7 months of age, respectively, were used. Animals were bred and housed in natural conditions and killed under light ether anesthesia. Throughout the experiments, care was taken to minimize pain or discomfort. All studies were approved by the Ioannina University Institutional Animal Care and Use Committee. Cortical front and rear tibia, as well as femoral neck, samples from 20 normal experimental animals, 10 Wistar rats, and 10 New Zealand albino rabbits, were analyzed. Half of each group of species was females and half males. The mean weight of the rats was 292 ± 10.6 g with a range from 280-300 g, while that of the rabbits was 2.46 ± 0.21 kg with a range from 2.2-2.7 kg. Preparation of Specimens for Electron Microscopy Samples of each chosen bone site were taken from the right side. They were carefully freed from soft tissue, and prepared for electron microscopy. The tissue was fixed in a solution containing 4 ml of 0.05 M phosphate buffer (pH 7.2), 0.5 ml of 25% glutaraldehyde, and 0.5 ml of 12.5% ethylene-diamine tetraacetic acid (EDTA) disodium salt. After 2 h, the bone was administered changes of 2 ml of EDTA in 3 ml of phosphate buffer until decalcified. Bone samples were trimmed into approximately 0.5mm 3 cubes and fixed in 2.5% glutaraldehyde in 0.05 M phosphate buffer (pH 7.2). Specimens were washed in the same buffer before and after fixation and rinsed in distilled water. Fixed specimens were then dehydrated in a graded alcohol series and impregnated overnight with 1:1 mixture of propylene oxide, and the resin used for embedding. Final embedding was performed in capsules with agar resin. Polymerization was completed in 48 h at 60 o C. Ultrathin sections were positively stained with 2% aqueous solution of phosphotungstic acid (PTA; pH 3.3) for 1 h and then with 2% aqueous solution of uranyl acetate (UA; pH 4.3) for 30 min, washing briefly in distilled water before and after UA staining. Electron Microscopy Electron microscopy was performed on a JEOL JEM 100 CX-II electron microscope and micrographs were taken at ×8,000-20,000. Grating replicas were used for magnification calibration. Morphometric Measurements For measurements of the diameter of collagen fibrils, areas of cross-sectional collagen were photographed. A minimum of 400 collagen fibrils from at least 4 micrographs were analyzed for each subject. Thus, as in each case 5 animals were involved, the diameters of at least 2,000 fibrils from 20 micrographs were averaged for each bone site. Measurements were made on prints from electron micrographs by the use of an algorithm developed in the laboratory. First the image of each electron micrograph, i.e., cross sections, was transferred by a GT 6000 Scanner to digital form and stored into the Berillis et al.: Bone Collagen Fibril Diameter TheScientificWorldJOURNAL (2006) 6, 1109-1113 1111 computer. This transfer was made using the program P-Styler with a resolution of at least 480 dpi. The digital image was converted into binary, through thresholding, by the program pixel.exe. A vertical and horizontal scanning of the final image was performed, in order to measure the dimensions and structural characteristics of each region. Fibril diameter is measured in pixels, which is subsequently converted to nm using the dpi of the transferred image. Further details appear in Tzaphlidou and Berillis Statistical analysis was performed according to Snedecor and Cochran[11] and Hays RESULTS DISCUSSION The samples processed for electron microscopy showed statistically significant differences in the collagen fibril diameter between different bone sites in most cases studied. The samples were made up of collagen fibrils from different genders and species. Berillis et al.: Bone Collagen Fibril Diameter TheScientificWorldJOURNAL (2006) 6, 1109-1113 The order of magnitude for mean diameter value is the same for females and males in both kinds of experimental animals. As it is shown in 1112 Similar variations in the mineral part (mean Ca/P ratios) of the above bone sites using the same kind of experimental animals have also been demonstrated It appears that a relationship exists between collagen fibril diameter and the Ca/P ratio for the same kind of experimental animal and bone site. Both of these parameters can be used as indexes of bone quality ACKNOWLEDGMENT

Status and Extension of the Geant4-DNA Dielectric Models for Application to Electron Transport

International audienceThe development of accurate physics models that enable track structure simulations of electrons in liquid water medium over a wide energy range, from the eV to the MeV scale, is a subject of continuous efforts due to its importance (among other things) in theoretical studies of radiation quality for application in radiotherapy and radiation protection. A few years ago, the Geant4-DNA very low-energy extension of the Geant4 Monte Carlo code had offered to users an improved set of physics models for discrete electron transport below 10 keV. In this work we present refinements to this model set and its extension to energies up to 1 MeV. Preliminary comparisons against the existing Geant4-DNA physics models with respect to total and differential ionization cross sections of electrons in liquid water are reported and discussed

Calculated electronic energy loss of swift proton and helium ion beams in liquid water

Paper submitted to the 9th International Conference on Applications of Nuclear Techniques, Crete, Greece, 8–14 June 2008.The electronic energy loss of swift proton and helium beams in liquid water is theoretically evaluated. Our model is based in the dielectric formalism, taking into account the charge exchange of the projectile during its travel through the target. The electronic properties of liquid water are described by the MELF-GOS model, where the outer electron excitations are represented by a sum of Mermin functions fitted to the experimental data in the optical limit, whereas the inner-shell electron excitations are modelled by the corresponding atomic generalized oscillator strength. The inverse mean free path, the stopping power and the energy loss straggling are calculated, showing a reasonably good agreement with the available experimental data.This work has been financially supported by the Spanish Ministerio de Educación y Ciencia (Contract Nos. FIS2006-13309-C02-01 and FIS2006-13309-C02-02). C.D.D. thanks the Spanish Ministerio de Educación y Ciencia for support under the Ramón y Cajal Program