Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement.

In addition to specific dosimetric properties of protons, their higher biological effectiveness makes them superior to X-rays and gamma radiation, in radiation therapy. In recent years, enrichment of tumours with metallic nanoparticles as radiosensitizer agents has generated high interest, with several studies attempting to confirm the efficacy of nanoparticles in proton therapy. In the present study Geant4 Monte Carlo (MC) code was used to quantify the increased nanoscopic dose deposition of 50 nm metallic nanoparticles including gold, bismuth, iridium, and gadolinium in water upon exposure to 5, 25, and 50 MeV protons. Dose enhancement factors, radial dose distributions in nano-scale, as well as secondary electron and photon energy spectra were calculated for the studied nanoparticles and proton beams. The obtained results demonstrated that in the presence of metallic nanoparticles an increase in proton energy leads to a decrease in secondary electron and photon production yield. Additionally, an increase in the radial dose enhancement factor from 1.4 to 16 was calculated for the studied nanoparticles when the proton energy was increased from 5 to 50 MeV. It is concluded that the dosimetric advantages of proton beams could be improved significantly in the presence of metallic nanoparticles.

High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study.

X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still limited to lighter elements (i.e., atomic number Z≤45). This study investigates the feasibility of focusing hard X-rays from solid-target tubes using ellipsoidal lens systems composed of mosaic graphite crystals with the aim of enabling high-resolution in vivo XFI applications with mid-Z (42≤Z≤64) elements. Monte Carlo simulations are performed to characterize the proposed focusing-optics concept and provide quantitative predictions of the XFI sensitivity, in silico tumor-bearing mice models loaded with palladium (Pd) and barium (Ba) NPs. Based on simulation results, the minimum detectable total mass of PdNPs per scan position is expected to be on the order of a few hundred nanograms under in vivo conform conditions. PdNP masses as low as 150 ng to 50 ng could be detectable with a resolution of 600 µm when imaging abdominal tumor lesions across a range of low-dose (0.8 µGy) to high-dose (8 µGy) exposure scenarios. The proposed focusing-optics concept presents a potential step toward realizing XFI with conventional X-ray tubes for high-resolution applications involving interesting NP formulations.

Ionization Detail Parameters for DNA Damage Evaluation in Charged Particle Radiotherapy: Simulation Study Based on Cell Survival Database.

Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing biological effects based on this quantification. This presents an opportunity to enhance the planning of charged particle radiotherapy by taking into account the ionization detail. This work uses Monte Carlo simulations with Geant4-DNA code for a wide variety of charged particles and their radiation qualities to analyze the distribution of ionization cluster sizes within nanometer-scale volumes, similar to DNA diameter. By correlating these results with biological parameters extracted from the PIDE database for the V79 cell line, a novel parameter R2 based on ionization details is proposed for the evaluation of radiation quality in terms of biological consequences, i.e., radiobiological cross section for inactivation. By incorporating the probability p of sub-lethal damage caused by a single ionization, we address limitations associated with the usually proposed nanodosimetric parameter Fk for characterizing the biological effects of radiation. We show that the new parameter R2 correlates well with radiobiological data and can be used to predict biological outcomes.

Identification of coal and gangue based on R value method for dual-energy X-ray of Geant4 simulation.

With technical means of Geant4 simulation, the effectiveness of R value method in coal and gangue identification method of dual-energy X-ray is verified, and the characteristic factors affecting R value are explored. In the experiment, control variable method is used to study the effect of the thickness and shape of coal and gangue in R threshold. Compared with the shape of the coal sample, the thickness of the sample can directly affect the changes in R value of coal and gangue more. In addition, R threshold is continuously changing during the process of coal and gangue separation. R value of coal and gangue is positively correlated with the thickness of the sample, while the correlation with shape is difficult to be expressed due to the difficulty of mathematical descriptions of shape. The results show that the combination of dual-energy X-ray and image processing of Geant4 simulation can effectively identify coal and gangue, and the accuracy of distinguishing coal and gangue with different shapes and thicknesses reaches 95%. Finally, the current use of Geant4 simulation based on sample thickness can establish R threshold change curve for coal and gangue separation under specific geological environment for further coal and gangue separation with R value method based on dual-energy.

Quantitative Assessment on Optical Properties as a Basis for Bioluminescence Imaging: An Experimental and Numerical Approach to the Transport of Optical Photons in Phantom Materials.

Bioluminescence imaging (BLI) is a widely used technique in preclinical scientific research, particularly in the development of mRNA-based medications and non-invasive tumor diagnostics. It has become an essential tool in current science. However, the current state of bioluminescence imaging is primarily qualitative, making it challenging to obtain quantitative measurements and to draw accurate conclusions. This fact is caused by the unique properties of optical photons and tissue interactions. In this paper, we propose an experimental setup and Geant4-simulations to gain a better understanding of the optical properties and processes involved in bioluminescence imaging. Our goal is to advance the field towards more quantitative measurements. We will discuss the details of our experimental setup, the data we collected, the outcomes of the Geant4-simulations, and additional information on the underlying physical processes.

Study of Nuclear Reactions in Therapy of Tumors with Proton Beams.

This paper presents an assessment of nuclear reaction yields of protons, α-particles, and neutrons in human tissue-equivalentmaterial in proton therapy using a simulation with Geant 4. In this study, we also check an enhancement of nuclear reactions due to the presence of Bi, Au, 11B, and 10B radiosensitizer nanoparticles. We demonstrate that a proton beam induces a noticeable amount of nuclear reactions in the tissue. Nevertheless, the enhancement of nuclear reaction products due to radiosensitizer nanoparticles is found to be negligible.

The effect of voxelization in Monte Carlo simulation to validate Bragg peak characteristics for a pencil proton beam.

Background: The purpose of this research was to show how the Bragg peak (BP) characteristics were affected by changing the voxel size in longitudinal and transverse directions in Monte Carlo (MC) simulations by using Geant4 and to calculate BP characteristics accurately by considering the voxel size effect for 68 MeV and 235.81 MeV. Materials and methods: Different interpolation techniques were applied to simulation data to find the closest results to the experimental data. Results: When the x-size of the voxel was increased 2 times at low energy, the maximum dose increase in the entrance and plateau regions were 17.8% and 17%, respectively, while BP curve shifted to the shallower region, resulting in a 0.5 mm reduction in the curable tumor width (W80pd). At high energy, the maximum dose increase at the entrance and plateau regions were 0.4% and 0.6%, respectively, while it was observed that W80pd did not change. When the y-z sizes of the voxel were increased 2 times at low energy, the maximum dose reduction at the entrance and plateau regions was 3.4%, but no change was observed in W80pd. At high energy, when the y-z sizes of the voxel were increased 2.2 times, the maximum dose reduction at the entrance and plateau regions were 8.9% and 9.1%, respectively, while W80pd increased by 0.5 mm. When linear, cubic spline, and Akima interpolations were applied to the simulation data, it was found that the results closest to the experimental data were obtained for Akima interpolations for both energies. Conclusion: it has been shown that the voxel size effect for the longitudinal direction was more effective at low energy than at high energy. However, the voxel size effect for the transverse direction was more effective for high energy.

InterDosi Monte Carlo simulations of photon and electron specific absorbed fractions in a voxel-based crab phantom.

InterDosi is a new in-house Monte Carlo code that aims at facilitating the use of the Geant4 toolkit for internal dosimetry using voxel-based phantoms. In the present work the dosimetric capabilities of this code are assessed by calculating self-irradiation specific absorbed fractions (SI-SAFs) in a voxel-based crab phantom. Recent standard human organ compositions and densities taken from ICRP Publication 110 have been used for material specifications of the four organs of a crab, namely, the heart, hepatopancreas, gills, and gonads, whereas the material assigned to the crab shell has been modeled based on literature values. The SI-SAFs were calculated for mono-energetic photons of energies between 10 and 4000 keV, and for mono-energetic electrons of energies between 100 and 4000 keV. The statistical errors corresponding to the calculated SI-SAFs were all less than 0.01%. The results obtained demonstrate that the simulated masses and volumes of the crab organs are in good agreement with those presented in the literature. In addition, the dosimetric results show that the calculated SI-SAFs are generally consistent with those reported in the literature, with some moderate differences due to differences in material specification. It is concluded that the InterDosi code can be successfully employed in internal dose estimations in small organisms, and it is suggested that material specifications specifically relating to crab tissues should be developed to provide more precise SI-SAFs.

Inactivation of SARS-CoV-2 by charged particles for Future Vaccine Production Applications: A Monte Carlo study.

The world is still suffering from the SARS-CoV-2 pandemic, and the number of infected people is still growing in many countries in 2022. Although great strides have been made to produce effective vaccines, efforts in this field should be accelerated, particularly due to the emergence of new variants. Using inactivated viruses is a conventional method of vaccine production. High levels of ionizing radiation can effectively inactivate viruses. Recently, studies on SARS-CoV-2 irradiation using low-LET radiations (e.g., gamma rays) have been performed. However, there are insufficient studies on the impact of charged particles on the inactivation of this virus. In this study, a realistic structure of SARS-CoV-2 is simulated by using Geant4 Monte Carlo toolkit, and the effect of electrons, protons, alphas, C-12, and Fe-56 ions on the inactivation of SARS-CoV-2 is investigated. The simulation results indicated that densely ionizing (high-LET) particles have the advantage of minimum number of damaged spike proteins per single RNA break. The RNA breaks induced by hydroxyl radicals produced in the surrounding water medium were significant only for electron beam radiation. Hence, indirect RNA breaks induced by densely ionizing particles is negligible. From a simulation standpoint, alpha particles (with energies up to 30 MeV) as well as C-12 ions (with energies up to 80 MeV/n), and Fe-56 ions (with any energy) can be introduced as particles of choice for effective SARS-CoV-2 inactivation.

Nanodosimetric Calculations of Radiation-Induced DNA Damage in a New Nucleus Geometrical Model Based on the Isochore Theory.

Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6-10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3-8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.

Nanoscale Calculation of Proton-Induced DNA Damage Using a Chromatin Geometry Model with Geant4-DNA.

Monte Carlo simulations can quantify various types of DNA damage to evaluate the biological effects of ionizing radiation at the nanometer scale. This work presents a study simulating the DNA target response after proton irradiation. A chromatin fiber model and new physics constructors with the ELastic Scattering of Electrons and Positrons by neutral Atoms (ELSEPA) model were used to describe the DNA geometry and the physical stage of water radiolysis with the Geant4-DNA toolkit, respectively. Three key parameters (the energy threshold model for strand breaks, the physics model and the maximum distance to distinguish DSB clusters) of scoring DNA damage were studied to investigate the impact on the uncertainties of DNA damage. On the basis of comparison of our results with experimental data and published findings, we were able to accurately predict the yield of various types of DNA damage. Our results indicated that the difference in physics constructor can cause up to 56.4% in the DNA double-strand break (DSB) yields. The DSB yields were quite sensitive to the energy threshold for strand breaks (SB) and the maximum distance to classify the DSB clusters, which were even more than 100 times and four times than the default configurations, respectively.

Secondary Electrons in Gold Nanoparticle Clusters and Their Role in Therapeutic Ratio: The Outcome of a Monte Carlo Simulation Study.

Gold nanoparticles (GNPs) are used in proton therapy radio-sensitizers to help increase the dose of radiation to targeted tumors by the emission of secondary electrons. Thus, this study aimed to investigate the link between secondary electron yields produced from a nanoshell of GNPs and dose absorption according to the distance from the center of the nanoparticles by using a Monte Carlo model. Microscopic evaluation was performed by modeling the interactions of secondary electrons in a phase-space file (PSF), where the number of emitted electrons was calculated within a spherical GNP of 15 nm along with the absorbed dose near it. Then, the Geant4-DNA physics list was used to facilitate the tracking of low-energy electrons down to an energy below 50 eV in water. The results show a remarkable change in the number of secondary electrons, which can be compared at concentrations less than and greater than 5 mg/mL, with increased secondary electron production exhibited around NPs within a distance of 10-100 nm from the surface of all nanospheres. It was found that there was a steep dose enhancement drop-off up to a factor of dose enhancement factor (DFE) ≤ 1 within a short distance of 100 nm from the surface of the GNPs, which revealed that the dose enhancement existed locally at nanometer distances from the GNPs. Overall, our results indicate that the physical interactions of protons with GNP clusters should not be considered as being directly responsible for the radio-sensitization effect, but should be regarded as playing a major role in NP properties and concentrations, which has a subsequent impact on local dose enhancement.

Experimental validation of proton physics models of Geant4 for calculating stopping power ratio.

In this work, we conducted experiments to validate the proton physics models of Geant4 (version 10.6). The stopping power ratios (SPRs) of 11 inserts, such as acrylic, delrin, high density polyethylene, and polytetrafluoroethylene, etc, were measured using a superconducting synchrocyclotron that produces a scattering proton beam. The SPRs of the inserts were also calculated based on Geant4 simulation with six physics lists, i.e. QGSP_ FTFP_ BERT, QGSP_BIC_HP, QGSP_BIC, QGSP_FTFP_BERT, QSGP_BERT, and QBBC. The calculated SPRs were compared to the experimental SPRs, and relative per cent error was used to quantify the accuracy of the simulated SPRs of inserts. The comparison showed that the five physics lists generally agree well with the experimental SPRs with a relative difference of less than 1%. The lowest overall percentage error was observed for QGSP_FTFP_BERT and the highest overall percentage error was observed for QGSP_BIC_HP. The 0.1 mm range cut value consistently led to higher percentage error for all physics lists except for QGSP_BIC_HP and QBBC. Based on the validation, we recommend QGSP_BERT_HP physics list for proton dose calculation.

Changes of the linear energy transfer (LET) and beam width of therapeutic carbon ion beam in density heterogeneous phantoms.

This work aims to investigate the changes in the linear energy transfer (LET) spectra distribution and the beam spot width of a therapeutic carbon ion beam in density heterogeneous phantoms. Three different heterogeneous phantoms were fabricated using a combination of solid water, lung, and bone tissue slabs and irradiated by a single energy carbon beam (276.5 MeV u-1). CR-39 detectors were used for experimental measurements and the Monte Carlo toolkit Geant4 was employed for theoretical simulations. The results demonstrated that the measured LET spectra agree well with the simulation results. The lung and bone tissues displayed no obvious effect on the spectral distribution of LET. The dose-average LET was invariant and showed no obvious difference in the different materials, while the track-average LET increased in the lung and decreased in the bone materials. Similarly, the beam spot size increased in the lung, and decreased in the bone materials. Additionally, the fluence of the secondary fragments varied in different tissues. These findings are expected to provide cross-validation data for the quality assurance of carbon ion therapy and to be beneficial for validating the base data in treatment planning systems.

Skin dose contamination conversion coefficients. Benchmark with three simulation codes.

Handling of radioactive material by operators can lead to contamination at the surface of the skin in case of an accident. The quantification of the dose received by the skin due to a contamination scenario is performed by means of dedicated dose coefficients as it is the case for other radiation protection dose quantities described in the literature. However, most available coefficients do not match realistic scenarios according to state-of-the-art of science and technology. Therefore, this work deals with dedicated dose conversion factors for skin contamination. Since there is an increasing demand on dose coefficients in general, these specific coefficients can be used for various calculations in radiation protection. In this work a method to evaluate such coefficients for the skin contamination dose related to photons, electrons, positrons, alpha and neutron particles is proposed. The coefficients are generated using Monte-Carlo simulations with three well established calculation codes (FLUKA, MCNP, and GEANT4). The results of the various codes are compared against each other for benchmarking purposes. The new dose coefficients allow the computation of the skin received dose, in the case of skin contamination scenario of an individual, taking into account the decay radiation of the radionuclides of interest. To benchmark the quantity derived here, comparisons of radionuclide contamination doses to the skin using the VARSKIN code available in the literature are performed with the results of this work.

UV radiation dose in real time with a cryogenic SiPM using Monte Carlo-Geant4 simulation.

At the moment, there is no method that allows the user to calculate the dose of UV radiation during the liquid nitrogen (LN2) sterilization process while complying with quality control regulations. This article describes a simulating method using Geant4 to obtain the dose of UV radiation in real-time with a cryogenic Silicon PhotoMultipliers (SiPM) inside the LN2 container. The results present the zone of minimum UV radiation and the estimation of the radiation dose with a cryogenic SiPM, located in the minimum zone to certify the absence of microorganisms in the LN2.

Development and validation of an analytical model allowing accurate predictions of gamma and electron beam dose distributions in a water medical phantom.

The aim of this work was to study photon and electron dose distributions in a phantom filled with water using the Monte Carlo Geant4 tool for electron energies ranging from 1 to 21 MeV and for photon energies ranging from 1.25 MeV to 25 MeV, corresponding to conventional radiotherapy Linac energies. The results of the Geant4 calculations were validated based on the relevant experimental data previously published. The results obtained were fitted and analytical models of dose distributions were developed for gamma radiation and electrons. For each of these models, one-dimensional (including dose depth profiles as a function of the depth inside the phantom) and two-dimensional (including the dose distribution as a function of depth and lateral position inside the phantom) dose distributions have been considered. Results are presented for photons and electrons of various energies. The coefficient of determination [Formula: see text] illustrates an excellent match between the developed analytical model and the Geant4 results. It is demonstrated that the analytical models developed in the present study can be applied in various fields such as those used for calibration applications and radiation therapy. It is concluded that the analytical models developed allow for quick, easy and reliable clinical dose estimates and offer promising alternatives to the standard tools and methods used in radiotherapy for treatment planning.

The Simulated Characterization and Suitability of Semiconductor Detectors for Strontium 90 Assay in Groundwater.

This paper examines the potential deployment of a 10 mm × 10 mm × 1 mm cadmium telluride detector for strontium-90 measurement in groundwater boreholes at nuclear decommissioning sites. Geant4 simulation was used to model the deployment of the detector in a borehole monitoring contaminated groundwater. It was found that the detector was sensitive to strontium-90, yttrium-90, caesium-137, and potassium-40 decay, some of the significant beta emitters found at Sellafield. However, the device showed no sensitivity to carbon-14 decay, due to the inability of the weak beta emission to penetrate both the groundwater and the detector shielding. The limit of detection for such a sensor when looking at solely strontium-90 decay was calculated as 323 BqL-1 after a 1-h measurement and 66 BqL-1 after a 24-h measurement. A gallium-arsenide (GaAs) sensor with twice the surface area, but 0.3% of the thickness was modelled for comparison. Using this sensor, sensitivity was increased, such that the limit of detection for strontium-90 was 91 BqL-1 after 1 h and 18 BqL-1 after 24 h. However, this sensor sacrifices the potential to identify the present radionuclides by their end-point energy. Additionally, the feasibility of using flexible detectors based on solar cell designs to maximise the surface area of detectors has been modelled.

Comparison of Neutron Detection Performance of Four Thin-Film Semiconductor Neutron Detectors Based on Geant4.

Third-generation semiconductor materials have a wide band gap, high thermal conductivity, high chemical stability and strong radiation resistance. These materials have broad application prospects in optoelectronics, high-temperature and high-power equipment and radiation detectors. In this work, thin-film solid state neutron detectors made of four third-generation semiconductor materials are studied. Geant4 10.7 was used to analyze and optimize detectors. The optimal thicknesses required to achieve the highest detection efficiency for the four materials are studied. The optimized materials include diamond, silicon carbide (SiC), gallium oxide (Ga2O3) and gallium nitride (GaN), and the converter layer materials are boron carbide (B4C) and lithium fluoride (LiF) with a natural enrichment of boron and lithium. With optimal thickness, the primary knock-on atom (PKA) energy spectrum and displacements per atom (DPA) are studied to provide an indication of the radiation hardness of the four materials. The gamma rejection capabilities and electron collection efficiency (ECE) of these materials have also been studied. This work will contribute to manufacturing radiation-resistant, high-temperature-resistant and fast response neutron detectors. It will facilitate reactor monitoring, high-energy physics experiments and nuclear fusion research.

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.