Modeling the effect of oxygen on the chemical stage of water radiolysis using GPU-based microscopic Monte Carlo simulations, with an application in FLASH radiotherapy

Abstract

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.

Recent Developments on gMicroMC: Transport Simulations of Proton and Heavy Ions and Concurrent Transport of Radicals and DNA

“…These consistencies motivated further studies with the concurrent simulation scheme while the expense was the lowered simulation efficiency. Our adoption of the GPU-based acceleration could shed light on this issue based on experiences from previous studies [ 9 , 27 , 28 , 61 ].…”

“…Later, we supported the physical track simulation for energetic electrons and implemented a DNA model of a lymphocyte cell nucleus at the base-pair resolution for the computation of electron-induced DNA damages [ 9 ]. Recently, we also included oxygen molecules in the chemical-stage simulation in a step-by-step manner, which enabled the study of the radiolytic depletion effect of dissolved oxygen molecules [ 28 ]. With these efforts, we were able to quantitatively study multiple critical problems that are computationally demanding.…”

“…For example, we performed comprehensive simulations with gMicroMC to answer how uncertainties from the simulation parameters affect the accuracy of the final DNA damage computations [ 29 ]. We also studied the radiolytic depletion of oxygen under ultra-high dose rate radiation (FLASH) to investigate the fundamental mechanism behind FLASH radiotherapy with the developed oxygen module in gMicroMC [ 28 ].…”

May oxygen depletion explain the FLASH effect? A chemical track structure analysis

“…Chemical inter-track effects (in the heterogeneous stage), in contrast, are not likely to take place. Most prominently, they affect OH• radicals and their recombinations [48,49,50] but also reduce oxygen consumption due to the competition of reactions (1) with recombination among the primary radicals [51,52]. The impact starts to be noticeable e. g. for 10 Gy delivered instantaneously [48].…”

“…In particular, Pratx and Kapp [23] applied a radiolytic oxygen depletion model with constant depletion rate, but accounting explicitly for diffusion, blood vessel perfusion and metabolic oxygen consumption, to conclude that oxygen depletion yields an OER modification only for hypoxic starting conditions. Full depletion of oxygen is found unlikely for a typical 30 Gy dose and very low oxygenation (0.01%) with a GPU-based Monte Carlo calculation [52]. A recent article by Petersson et al [26] presents a simplified mathematical framework to describe oxygen variation including reoxygenation during irradiation which can be adjusted to reproduce some experimental findings under FLASH conditions [16,18].…”