A digital male pelvis phantom series showing anatomical variations over the course of fractionated radiotherapy treatment.

BACKGROUND: Daily IGRT images show day-to-day anatomical variations in patients undergoing fractionated prostate radiotherapy. This is of particular importance in particle beam treatments. PURPOSE: To develop a digital phantom series showing variation in pelvic anatomy for evaluating treatment planning and IGRT procedures in particle radiotherapy. METHODS: A pelvic phantom series was developed from the planning MRI and kVCT (planning CT) images along with six of the daily serial MVCT images taken of a single patient treated with a full bladder on a Tomotherapy unit. The selected patient had clearly visible yet unexceptional internal anatomy variation. Prostate, urethra, bladder, rectum, bowel, bowel gas, bone and soft tissue were contoured and a single Hounsfield Unit was assigned to each region. Treatment plans developed on the kVCT for photon, proton and carbon beams were recalculated on each phantom to demonstrate a clinical application of the series. Proton plans were developed with and without robust optimization. RESULTS: Limited to axial slices with prostate, the bladder volume varied from 6 to 46 cm3, the rectal volume (excluding gas) from 22 to 52 cm3, and rectal gas volume from zero to 18 cm3. The water equivalent path length to the prostate varied by up to 1.5 cm . The variations resulted in larger changes in the RBE-weighted Dose Volume Histograms of the non-robust proton plan and the carbon plan compared to the robust proton plan, the latter similar to the photon plan. The prostate coverage (V100%) decreased by an average of 18% in the carbon plan, 16% in the non-robust proton plan, 1.8% in the robust proton plan, and 4.4% in the photon plan. The volume of rectum receiving 75% of the prescription dose (V75%) increased by an average of 3.7 cm3, 4.7 cm3, 1.9 cm3, and 0.6 cm3 in those four plans, respectively. CONCLUSIONS: The digital pelvic phantom series provides for quantitative investigation of IGRT procedures and new methods for improving accuracy in particle therapy and may be used in cross-institutional comparisons for clinical trial quality assurance.

Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods.

Purpose: Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (64Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations. Methods: A mammalian cell nucleus model with a diameter of 9.3 µm available in TOPAS-nBio was used. The cellular nucleus consisted of double-helix DNA geometrical model of 2.3 nm diameter surrounded by a hydration shell with a thickness of 0.16 nm, organized in 46 chromosomes giving a total of 6.08 giga base-pairs (DNA density of 14.4 Mbp/µm3). The cellular nucleus was irradiated with monoenergetic electrons and radiation emissions from several radionuclides including 111In, 125I, 123I, and 99mTc in addition to 64Cu. For monoenergetic electrons, isotropic point sources randomly distributed within the nucleus were modeled. The radionuclides were incorporated in randomly chosen DNA base pairs at two positions near to the central axis of the double-helix DNA model at (1) 0.25 nm off the central axis and (2) at the periphery of the DNA (1.15 nm off the central axis). For all the radionuclides except for 99mTc, the complete physical decay process was explicitly simulated. For 99mTc only total electron spectrum from published data was used. The DNA Double Strand Breaks (DSB) yield per decay from direct and indirect actions were quantified. Results obtained for monoenergetic electrons and radionuclides 111In, 125I, 123I, and 99mTc were compared with measured and calculated data from the literature for verification purposes. The DSB yields per decay incorporated in DNA for 64Cu are first reported in this work. The therapeutic effect of 64Cu (activity that led 37% cell survival after two cell divisions) was determined in terms of the number of atoms incorporated into the nucleus that would lead to the same DSBs that 100 decays of 125I. Simulations were run until a 2% statistical uncertainty (1 standard deviation) was achieved. Results: The behavior of DSBs as a function of the energy for monoenergetic electrons was consistent with published data, the DSBs increased with the energy until it reached a maximum value near 500 eV followed by a continuous decrement. For 64Cu, when incorporated in the genome at evaluated positions (1) and (2), the DSB were 0.171 ± 0.003 and 0.190 ± 0.003 DSB/decay, respectively. The number of initial atoms incorporated into the genome (per cell) for 64Cu that would cause a therapeutic effect was estimated as 3,107 ± 28, that corresponds to an initial activity of 47.1 ± 0.4 × 10-3 Bq. Conclusion: Our results showed that TRT with 64Cu has comparable therapeutic effects in cells as that of TRT with radionuclides currently used in clinical practice.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy.

Objective. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP).Approach. Our model provides for selection of preferred ID parameters (Ip) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopicIpand macroscopic RTP. Selection ofIpis demonstrated using published cell survival measurements for protons through argon, comparing results for nineteenIp:Nk,k= 2, 3, …, 10, the number of ionizations in clusters ofkor more per particle, andFk,k= 1, 2, …, 10, the number of clusters ofkor more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation.Main results. The preferredIpwereN4andF5for aerobic cells,N5andF7for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferredNk. Conversely, there was no significant difference forF5for aerobic cells andF7for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for theseIphad the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert thatIpexist that are more closely associated with biological effects than current LET-based approaches and microdosimetric RBE-based models used in particle RTP. However, more biological variables such as cell line and cycle phase, as well as ion beam pulse structure and rate still need investigation.Significance. Our model provides a practical means to select preferredIpfrom radiobiological data, and to convertIpto the macroscopic cluster dose for particle RTP.

An integrated Monte Carlo track-structure simulation framework for modeling inter and intra-track effects on homogenous chemistry.

Objective. The TOPAS-nBio Monte Carlo track structure simulation code, a wrapper of Geant4-DNA, was extended for its use in pulsed and longtime homogeneous chemistry simulations using the Gillespie algorithm.Approach. Three different tests were used to assess the reliability of the implementation and its ability to accurately reproduce published experimental results: (1) a simple model with a known analytical solution, (2) the temporal evolution of chemical yields during the homogeneous chemistry stage, and (3) radiolysis simulations conducted in pure water with dissolved oxygen at concentrations ranging from 10µM to 1 mM with [H2O2] yields calculated for 100 MeV protons at conventional and FLASH dose rates of 0.286 Gy s-1and 500 Gy s-1, respectively. Simulated chemical yield results were compared closely with data calculated using the Kinetiscope software which also employs the Gillespie algorithm.Main results. Validation results in the third test agreed with experimental data of similar dose rates and oxygen concentrations within one standard deviation, with a maximum of 1% difference for both conventional and FLASH dose rates. In conclusion, the new implementation of TOPAS-nBio for the homogeneous long time chemistry simulation was capable of recreating the chemical evolution of the reactive intermediates that follow water radiolysis.Significance. Thus, TOPAS-nBio provides a reliable all-in-one chemistry simulation of the physical, physico-chemical, non-homogeneous, and homogeneous chemistry and could be of use for the study of FLASH dose rate effects on radiation chemistry.

GEANT4-DNA simulation of temperature-dependent and pH-dependent yields of chemical radiolytic species.

Objective.GEANT4-DNA can simulate radiation chemical yield (G-value) for radiolytic species such as the hydrated electron (eaq-) with the independent reaction times (IRT) method, however, only at room temperature and neutral pH. This work aims to modify the GEANT4-DNA source code to enable the calculation ofG-values for radiolytic species at different temperatures and pH values.Approach.In the GEANT4-DNA source code, values of chemical parameters such as reaction rate constant, diffusion coefficient, Onsager radius, and water density were replaced by corresponding temperature-dependent polynomials. The initial concentration of hydrogen ion (H+)/hydronium ion (H3O+) was scaled for a desired pH using the relationship pH = -log10[H+]. To validate our modifications, two sets of simulations were performed. (A) A water cube with 1.0 km sides and a pH of 7 was irradiated with an isotropic electron source of 1 MeV. The end time was 1µs. The temperatures varied from 25 °C to 150 °C. (B) The same setup as (A) was used, however, the temperature was set to 25 °C while the pH varied from 5 to 9. The results were compared with published experimental and simulated work.Main results.The IRT method in GEANT4-DNA was successfully modified to simulateG-values for radiolytic species at different temperatures and pH values. Our temperature-dependent results agreed with experimental data within 0.64%-9.79%, and with simulated data within 3.52%-12.47%. The pH-dependent results agreed well with experimental data within 0.52% to 3.19% except at a pH of 5 (15.99%) and with simulated data within 4.40%-5.53%. The uncertainties were below ±0.20%. Overall our results agreed better with experimental than simulation data.Significance.Modifications in the GEANT4-DNA code enabled the calculation ofG-values for radiolytic species at different temperatures and pH values.

Dosimetric characterization of single- and dual-port temporary tissue expanders for postmastectomy radiotherapy using Monte Carlo methods.

Purpose: The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE. Methods: The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1). 2) Registering a geometry template with dimensions and materials from the TTEs (RS2). Both strategies were compared for DermaSpan, AlloX2, and AlloX2-Pro TTEs using Collapsed Cone Convolution (CCC) in RayStation TPS, Monte Carlo simulations (MC) using TOPAS, and film measurements. Wax slab phantoms with metallic ports and breast phantoms with TTEs balloons were made and irradiated with a 6 MV AP beam and partial arc, respectively. Dose values along the AP direction calculated with CCC (RS2) and TOPAS (RS1 and RS2) were compared with film measurements. The impact in dose distributions was evaluated with RS2 by comparing TOPAS simulations with and without the metal port. Results: For the wax slab phantoms, the dose differences between RS1 and RS2 were 0.5% for DermaSpan and AlloX2 but 3% for AlloX2-Pro. From TOPAS simulations of RS2, the impact in dose distributions caused by the magnet attenuation was (6.4 ± 0.4) %, (4.9 ± 0.7)%, and (2.0 ± 0.9)% for DermaSpan, AlloX2, and AlloX2-Pro, respectively. With breast phantoms, maximum differences in DVH parameters between RS1 and RS2 were as follows. For AlloX2 at the posterior region: (2.1 ± 1.0)%, (1.9 ± 1.0)% and (1.4 ± 1.0)% for D1, D10, and average dose, respectively. For AlloX2-Pro at the anterior region (-1.0 ± 1.0)%, (-0.6 ± 1.0)% and (-0.6 ± 1.0)% for D1, D10 and average dose, respectively. The impact in D10 caused by the magnet was at most (5.5 ± 1.0)% and (-0.8 ± 1.0)% for AlloX2 and AlloX2-Pro, respectively. Conclusion: Two strategies for accounting for CT artifacts from three breast TTEs were assessed using CCC, MC, and film measurements. This study showed that the highest differences with respect to measurements occurred with RS1 and can be mitigated if a template with the actual port geometry and materials is used.

Microdosimetric Analysis for Boron Neutron Capture Therapy via Monte Carlo Track Structure Simulation with Modified Lithium Cross-sections.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development.

TOPAS-imaging: extensions to the TOPAS simulation toolkit for medical imaging systems.

Objective. The TOol for PArticle Simulation (TOPAS) is a Geant4-based Monte Carlo software application that has been used for both research and clinical studies in medical physics. So far, most users of TOPAS have focused on radiotherapy-related studies, such as modeling radiation therapy delivery systems or patient dose calculation. Here, we present the first set of TOPAS extensions to make it easier for TOPAS users to model medical imaging systems.Approach. We used the extension system of TOPAS to implement pre-built, user-configurable geometry components such as detectors (e.g. flat-panel and multi-planar detectors) for various imaging modalities and pre-built, user-configurable scorers for medical imaging systems (e.g. digitizer chain).Main results. We developed a flexible set of extensions that can be adapted to solve research questions for a variety of imaging modalities. We then utilized these extensions to model specific examples of cone-beam CT (CBCT), positron emission tomography (PET), and prompt gamma (PG) systems. The first of these new geometry components, the FlatImager, was used to model example CBCT and PG systems. Detected signals were accumulated in each detector pixel to obtain the intensity of x-rays penetrating objects or prompt gammas from proton-nuclear interaction. The second of these new geometry components, the RingImager, was used to model an example PET system. Positron-electron annihilation signals were recorded in crystals of the RingImager and coincidences were detected. The simulated data were processed using corresponding post-processing algorithms for each modality and obtained results in good agreement with the expected true signals or experimental measurement.Significance. The newly developed extension is a first step to making it easier for TOPAS users to build and simulate medical imaging systems. Together with existing TOPAS tools, this extension can help integrate medical imaging systems with radiotherapy simulations for image-guided radiotherapy.

Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA.

PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Development of Ultra-High Dose-Rate (FLASH) Particle Therapy.

Research efforts in FLASH radiotherapy have increased at an accelerated pace recently. FLASH radiotherapy involves ultra-high dose rates and has shown to reduce toxicity to normal tissue while maintaining tumor response in pre-clinical studies when compared to conventional dose rate radiotherapy. The goal of this review is to summarize the studies performed to-date with proton, electron, and heavy ion FLASH radiotherapy, with particular emphasis on the physical aspects of each study and the advantages and disadvantages of each modality. Beam delivery parameters, experimental set-up, and the dosimetry tools used are described for each FLASH modality. In addition, modeling efforts and treatment planning for FLASH radiotherapy is discussed along with potential drawbacks when translated into the clinical setting. The final section concludes with further questions that have yet to be answered before safe clinical implementation of FLASH radiotherapy.

TOPAS-nBio simulation of temperature-dependent indirect DNA strand break yields.

Current Monte Carlo simulations of DNA damage have been reported only at ambient temperature. The aim of this work is to use TOPAS-nBio to simulate the yields of DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) produced in plasmids under low-LET irradiation incorporating the effect of the temperature changes in the environment. A new feature was implemented in TOPAS-nBio to incorporate reaction rates used in the simulation of the chemical stage of water radiolysis as a function of temperature. The implemented feature was verified by simulating temperature-dependentG-values of chemical species in liquid water from 20 °C to 90 °C. For radiobiology applications, temperature dependent SSB and DSB yields were calculated from 0 °C to 42 °C, the range of available published measured data. For that, supercoiled DNA plasmids dissolved in aerated solutions containing EDTA irradiated by Cobalt-60 gamma-rays were simulated. TOPAS-nBio well reproduced published temperature-dependentG-values in liquid water and the yields of SSB and DSB for the temperature range considered. For strand break simulations, the model shows that the yield of SSB and DSB increased linearly with the temperature at a rate of (2.94 ± 0.17) × 10-10Gy-1Da-1°C-1(R2 = 0.99) and (0.13 ± 0.01) × 10-10Gy-1Da-1°C-1(R2 = 0.99), respectively. The extended capability of TOPAS-nBio is a complementary tool to simulate realistic conditions for a large range of environmental temperatures, allowing refined investigations of the biological effects of radiation.

Impact of DNA Geometry and Scoring on Monte Carlo Track-Structure Simulations of Initial Radiation-Induced Damage.

Track structure Monte Carlo simulations are a useful tool to investigate the damage induced to DNA by ionizing radiation. These simulations usually rely on simplified geometrical representations of the DNA subcomponents. DNA damage is determined by the physical and physicochemical processes occurring within these volumes. In particular, damage to the DNA backbone is generally assumed to result in strand breaks. DNA damage can be categorized as direct (ionization of an atom part of the DNA molecule) or indirect (damage from reactive chemical species following water radiolysis). We also consider quasi-direct effects, i.e., damage originated by charge transfers after ionization of the hydration shell surrounding the DNA. DNA geometries are needed to account for the damage induced by ionizing radiation, and different geometry models can be used for speed or accuracy reasons. In this work, we use the Monte Carlo track structure tool TOPAS-nBio, built on top of Geant4-DNA, for simulation at the nanometer scale to evaluate differences among three DNA geometrical models in an entire cell nucleus, including a sphere/spheroid model specifically designed for this work. In addition to strand breaks, we explicitly consider the direct, quasi-direct, and indirect damage induced to DNA base moieties. We use results from the literature to determine the best values for the relevant parameters. For example, the proportion of hydroxyl radical reactions between base moieties was 80%, and between backbone, moieties was 20%, the proportion of radical attacks leading to a strand break was 11%, and the expected ratio of base damages and strand breaks was 2.5-3. Our results show that failure to update parameters for new geometric models can lead to significant differences in predicted damage yields.

The relation between microdosimetry and induction of direct damage to DNA by alpha particles.

In radiopharmaceutical treatmentsα-particles are employed to treat tumor cells. However, the mechanism that drives the biological effect induced is not well known. Being ionizing radiation,α-particles can affect biological organisms by producing damage to the DNA, either directly or indirectly. Following the principle that microdosimetry theory accounts for the stochastic way in which radiation deposits energy in sub-cellular sized volumes via physical collisions, we postulate that microdosimetry represents a reasonable framework to characterize the statistical nature of direct damage induction byα-particles to DNA. We used the TOPAS-nBio Monte Carlo package to simulate direct damage produced by monoenergetic alpha particles to different DNA structures. In separate simulations, we obtained the frequency-mean lineal energy (yF) and dose-mean lineal energy (yD) of microdosimetric distributions sampled with spherical sites of different sizes. The total number of DNA strand breaks, double strand breaks (DSBs) and complex strand breaks per track were quantified and presented as a function of eitheryForyD.The probability of interaction between a track and the DNA depends on how the base pairs are compacted. To characterize this variability on compactness, spherical sites of different size were used to match these probabilities of interaction, correlating the size-dependent specific energy (z) with the damage induced. The total number of DNA strand breaks per track was found to linearly correlate withyFandzFwhen using what we defined an effective volume as microdosimetric site, while the yield of DSB per unit dose linearly correlated withyDorzD,being larger for compacted than for unfolded DNA structures. The yield of complex breaks per unit dose exhibited a quadratic behavior with respect toyDand a greater difference among DNA compactness levels. Microdosimetric quantities correlate with the direct damage imparted on DNA.

Geant4-DNA simulation of the pre-chemical stage of water radiolysis and its impact on initial radiochemical yields.

This paper demonstrates the impact of the pre-chemical stage, especially the dissociation scheme and the associated probabilities, on water radiolysis simulation using the Geant4-DNA Monte Carlo track structure simulation toolkit. The models and parameters provided by TRACs have been collected and implemented into Geant4-DNA. In order to evaluate their influence on water radiolysis simulation, the radiochemical yields (G-values) are evaluated as a function of time and LET using the "chem6" Geant4-DNA example, and they are compared with published experimental and calculated data. The new pre-chemical models lead to a better agreement with literature data than the default pre-chemical models of Geant4-DNA, especially for OH radicals and H2O2. The revised chemistry constructor "G4EmDNAChemistry_option3" is available in Geant4-DNA version 10.7.

On the Equivalence of the Biological Effect Induced by Irradiation of Clusters of Heavy Atom Nanoparticles and Homogeneous Heavy Atom-Water Mixtures.

A multiscale local effect model (LEM)-based framework was implemented to study the cell damage caused by the irradiation of clusters of gold nanoparticles (GNPs) under clinically relevant conditions. The results were compared with those obtained by a homogeneous mixture of water and gold (MixNP) irradiated under similar conditions. To that end, Monte Carlo simulations were performed for the irradiation of GNP clusters of different sizes and MixNPs with a 6 MV Linac spectrum to calculate the dose enhancement factor in water. The capabilities of our framework for the prediction of cell damage trends are examined and discussed. We found that the difference of the main parameter driving the cell damage between a cluster of GNPs and the MixNP was less than 1.6% for all cluster sizes. Our results demonstrate for the first time a simple route to intuit the radiobiological effects of clusters of nanoparticles through the consideration of an equivalent homogenous gold/water mixture. Furthermore, the negligible difference on cell damage between a cluster of GNPs and MixNP simplifies the modelling for the complex geometries of nanoparticle aggregations and saves computational resources.

Validation of the TOPAS Monte Carlo toolkit for HDR brachytherapy simulations.

PURPOSE: The goal of this work is to validate the user-friendly Geant4-based Monte Carlo toolkit TOol for PArticle Simulation (TOPAS) for brachytherapy applications. METHODS AND MATERIALS: Brachytherapy simulations performed with TOPAS were systematically compared with published TG-186 reference data. The photon emission energy spectrum, the air-kerma strength, and the dose-rate constant of the model-based dose calculation algorithm (MBDCA)-WG generic Ir-192 source were extracted. For dose calculations, a track-length estimator was implemented. The four Joint AAPM/ESTRO/ABG MBDCA-WG test cases were evaluated through histograms of the local and global dose difference volumes. A prostate, a palliative lung, and a breast case were simulated. For each case, the dose ratio map, the histogram of the global dose difference volume, and cumulative dose-volume histograms were calculated. RESULTS: The air-kerma strength was (9.772 ± 0.001) × 10-8 U Bq-1 (within 0.3% of the reference value). The dose-rate constant was 1.1107 ± 0.0005 cGy h-1 U-1 (within 0.01% of the reference value). For all cases, at least 96.9% of voxels had a local dose difference within [-1%, 1%] and at least 99.9% of voxels had a global dose difference within [-0.1%, 0.1%]. The implemented track-length estimator scorer was more efficient than the default analog dose scorer by a factor of 237. For all clinical cases, at least 97.5% of voxels had a global dose difference within [-1%, 1%]. Dose-volume histograms were consistent with the reference data. CONCLUSIONS: TOPAS was validated for high-dose-rate brachytherapy simulations following the TG-186 recommended approach for MBDCAs. Built on top of Geant4, TOPAS provides broad access to a state-of-the-art Monte Carlo code for brachytherapy simulations.

Dispersion calibration for the National Ignition Facility electron-positron-proton spectrometers for intense laser matter interactions.

Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility Electron-Positron-Proton Spectrometers (EPPSs). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement quality. The dispersion of low-energy electrons and positrons may be affected by fringe magnetic fields near the entrance of the EPPS. We have calibrated the EPPS with six electron beams from a Siemens Oncor linear accelerator (linac) ranging in energy from 2.7 MeV to 15.2 MeV as they enter the spectrometer. A Geant4 traveling-wave optical parametric amplifier of superfluorescence Monte Carlo simulation was set up to match depth dose curves and lateral profiles measured in water at 100 cm source-surface distance. An accurate relationship was established between the bending magnet current setting and the energy of the electron beam at the exit window. The simulations and measurements were used to determine the energy distributions of the six electron beams at the EPPS slit. Analysis of the scanned image plates together with the determined energy distribution arriving in the spectrometer provides improved dispersion curves for the EPPS.

Boronated Condensed DNA as a Heterochromatic Radiation Target Model.

The compound 4-dihydroxyboryl-l-phenylalanine (BPA) has found use in clinical trials of boron neutron capture therapy (BNCT). Here, we have examined the interaction with DNA of an amide-blocked BPA derivative of hexa-l-arginine (Ac-BPA-Arg6-NH2). Physical and spectroscopic assays show that this peptide binds to and condenses DNA. The resulting condensates are highly resistant to the effects of nuclease incubation (68-fold) and gamma (38-fold) irradiation. Radioprotection was modeled by Monte Carlo track structure simulations of DNA single strand breaks (SSBs) with TOPAS-nBio. The differences between experimental and simulated SSB yields for uncondensed and condensed DNAs were ca. 2 and 18%, respectively. These observations indicate that the combination of a plasmid DNA target, the BPA-containing peptide, and track structure simulation provides a powerful approach to characterize DNA damage by the high-LET radiation associated with neutron capture on boron.