Oxygen plays a critical role in determining the initial DNA damages induced by ionizing radiation. It is important to mechanistically model the oxygen effect in the water radiolysis process. However, due to the computational costs from the many body interaction problem, oxygen is often ignored or treated as a constant continuum radiolysis-scavenger background in the simulations using common microscopic Monte Carlo tools. In this work, we reported our recent progress on the modeling of the chemical stage of the water radiolysis with an explicit consideration of the oxygen effect, based upon our initial development of an open-source graphical processing unit (GPU)-based MC simulation tool, gMicroMC. The inclusion of oxygen mainly reduces the yields of e h and H . chemical radicals, turning them into highly toxic O 2 . − and H O 2 . species. To demonstrate the practical value of gMicroMC in large scale simulation problems, we applied the oxygen-simulation-enabled gMicroMC to compute the yields of chemical radicals under a high instantaneous dose rate D ˙ i to study the oxygen depletion hypothesis in FLASH radiotherapy. A decreased oxygen consumption rate (OCR) was found associated with a reduced initial oxygen concentration level due to reduced probabilities of reactions. With respect to dose rate, for the oxygen concentration of 21% and electron energy of 4.5 k e V , OCR remained approximately constant (∼0.22 μ M   G y − 1 ) for D ˙ i ’s of 10 6 , 10 7   G y s − 1 and reduced to 0.19 μ M   G y − 1 at 10 8   G y s − 1 , because the increased dose rate improved the mutual reaction frequencies among radicals, hence reducing their reactions with oxygen. We computed the time evolution of oxygen concentration under the FLASH irradiation setups. At the dose rate of 10 7   G y s − 1 and initial oxygen concentrations from 0.01% to 21%, the oxygen is unlikely to be fully depleted with an accumulative dose of 30 Gy, which is a typical dose used in FLASH experiments. The computational efficiency of gMicroMC when considering oxygen molecules in the chemical stage was evaluated through benchmark work to GEANT4-DNA with simulating an equivalent number of radicals. With an initial oxygen concentration of 3% (∼105 molecules), a speedup factor of 1228 was achieved for gMicroMC on a single GPU card when comparing with GEANT4-DNA on a single CPU.

Purpose: Monte Carlo (MC) simulation of radiation interactions with water medium at physical, physicochemical, and chemical stages, as well as the computation of biologically relevant quantities such as DNA damages, are of critical importance for the understanding of microscopic basis of radiation effects. Due to the large problem size and many-body simulation problem in the chemical stage, existing CPU-based computational packages encounter the problem of low computational efficiency. This paper reports our development on a GPU-based microscopic Monte Carlo simulation tool gMi-croMC using advanced GPU-acceleration techniques. Methods: gMicroMC simulated electron transport in the physical stage using an interaction-by-interaction scheme to calculate the initial events generating radicals in water. After the physicochemical stage, initial positions of all radicals were determined. Simulation of radicals' diffusion and reactions in the chemical stage was achieved using a step-by-step model using GPU-accelerated parallelization together with a GPU-enabled box-sorting algorithm to reduce the computations of searching for interaction pairs and therefore improve efficiency. A multi-scale DNA model of the whole lymphocyte cell nucleus containing~6.2 Gbp of DNA was built. Results: Accuracy of physical stage simulation was demonstrated by computing stopping power and track length. The results agreed with published data and the data produced by GEANT4-DNA (version 10.3.3) simulations with 10 -20% difference in most cases. Difference of yield values of major radiolytic species from GEANT4-DNA results was within 10%. We computed DNA damages caused by monoenergetic 662 keV photons, approximately representing 137 Cs decay. Single-strand break (SSB) and double-strand break (DSB) yields were 196 AE 8 SSB/Gy/Gbp and 7.3 AE 0.7 DSB/Gy/ Gbp, respectively, which agreed with the result of 188 SSB/Gy/Gbp and 8.4 DSB/Gy/Gbp computed by Hsiao et al. Compared to computation using a single CPU, gMicroMC achieved a speedup factor of~540x using an NVidia TITAN Xp GPU card. Conclusions:The achieved accuracy and efficiency demonstrated that gMicroMC can facilitate research on microscopic radiation transport simulation and DNA damage calculation. gMicroMC is an open-source package available to the research community.

With the goal of developing a total-body small-animal PET system with a high spatial resolution of ∼0.5 mm and a high sensitivity >10% for mouse/rat studies, we simulated four scanners using the graphical processing unit-based Monte Carlo simulation package (gPET) and compared their performance in terms of spatial resolution and sensitivity. We also investigated the effect of depth-of-interaction (DOI) resolution on the spatial resolution. All the scanners are built upon 128 DOI encoding dual-ended readout detectors with lutetium yttrium oxyorthosilicate (LYSO) arrays arranged in 8 detector rings. The solid angle coverages of the four scanners are all ∼0.85 steradians. Each LYSO element has a cross-section of 0.44 × 0.44 mm2 and the pitch size of the LYSO arrays are all 0.5 mm. The four scanners can be divided into two groups: (1) H2RS110-C10 and H2RS110-C20 with 40 × 40 LYSO arrays, a ring diameter of 110 mm and axial length of 167 mm, and (2) H2RS160-C10 and H2RS160-C20 with 60 × 60 LYSO arrays, a diameter of 160 mm and axial length of 254 mm. C10 and C20 denote the crystal thickness of 10 and 20 mm, respectively. The simulation results show that all scanners have a spatial resolution better than 0.5 mm at the center of the field-of-view (FOV). The radial resolution strongly depends on the DOI resolution and radial offset, but not the axial resolution and tangential resolution. Comparing the C10 and C20 designs, the former provides better resolution, especially at positions away from the center of the FOV, whereas the latter has 2× higher sensitivity (∼10% versus ∼20%). This simulation study provides evidence that the 110 mm systems are a good choice for total-body mouse studies at a lower cost, whereas the 160 mm systems are suited for both total-body mouse and rat studies.

Purpose: Calculations of deoxyribonucleic acid (DNA) damages involve many parameters in the computation process. As these parameters are often subject to uncertainties, it is of central importance to comprehensively quantify their impacts on DNA single-strand break (SSB) and doublestrand break (DSB) yields. This has been a challenging task due to the required large number of simulations and the relatively low computational efficiency using CPU-based MC packages. In this study, we present comprehensive evaluations on sensitivities and uncertainties of DNA SSB and DSB yields on 12 parameters using our GPU-based MC tool, gMicroMC. Methods: We sampled one electron at a time in a water sphere containing a human lymphocyte nucleus and transport the electrons and generated radicals until 2 Gy dose was accumulated in the nucleus. We computed DNA damages caused by electron energy deposition events in the physical stage and the hydroxyl radicals at the end of the chemical stage. We repeated the computations by varying 12 parameters: (a) physics cross section, (b) cutoff energy for electron transport, (c)-(e) three branching ratios of hydroxyl radicals in the de-excitation of excited water molecules, (f) temporal length of the chemical stage, (g)-(h) reaction radii for direct and indirect damages, (i) threshold energy defining the threshold damage model to generate a physics damage, (j)-(k) minimum and maximum energy values defining the linear-probability damage model to generate a physics damage, and (l) probability to generate a damage by a radical. We quantified sensitivity of SSB and DSB yields with respect to these parameters for cases with 1.0 and 4.5 keV electrons. We further estimated uncertainty of SSB and DSB yields caused by uncertainties of these parameters. Results: Using a threshold of 10% uncertainty as a criterion, threshold energy in the threshold damage model, maximum energy in the linear-probability damage model, and probability for a radical to generate a damage were found to cause large uncertainties in both SSB and DSB yields. The scaling factor of the cross section, cutoff energy, physics reaction radius, and minimum energy in the linearprobability damage model were found to generate large uncertainties in DSB yields. Conclusions: We identified parameters that can generate large uncertainties in the calculations of SSB and DSB yields. Our study could serve as a guidance to reduce uncertainties of parameters and hence uncertainties of the simulation results.

High dose rate (HDR) brachytherapy treatment planning is conventionally performed manually and/or with aids of preplanned templates. In general, the standard of care would be elevated by conducting an automated process to improve treatment planning efficiency, eliminate human error, and reduce plan quality variations. Thus, our group is developing AutoBrachy, an automated HDR brachytherapy planning suite of modules used to augment a clinical treatment planning system. This paper describes our proof-of-concept module for vaginal cylinder HDR planning that has been fully developed. After a patient CT scan is acquired, the cylinder applicator is automatically segmented using image-processing techniques. The target CTV is generated based on physician-specified treatment depth and length. Locations of the dose calculation point, apex point and vaginal surface point, as well as the central applicator channel coordinates, and the corresponding dwell positions are determined according to their geometric relationship with the applicator and written to a structure file. Dwell times are computed through iterative quadratic optimization techniques. The planning information is then transferred to the treatment planning system through a DICOM-RT interface. The entire process was tested for nine patients. The AutoBrachy cylindrical applicator module was able to generate treatment plans for these cases with clinical grade quality. Computation times varied between 1 and 3 min on an Intel Xeon CPU E3-1226 v3 processor. All geometric components in the automated treatment plans were generated accurately. The applicator channel tip positions agreed with the manually identified positions with submillimeter deviations and the channel orientations between the plans agreed within less than 1 degree. The automatically generated plans obtained clinically acceptable quality.