A GPU‐based Monte Carlo model for water radiolysis under ultra‐high dose rate irradiation: Development and validation with MPEXS2.1‐DNA

Abstract

Background
FLASH radiotherapy using ultra‐high dose rates (UHDR, > 40 Gy/s) demonstrates significant healthy‐tissue sparing while maintaining tumor‐control effectiveness. However, the underlying mechanisms remain unclear, with hypotheses suggesting that reductions in reactive oxygen species (ROS) yields could contribute to the FLASH effect. Direct experimental measurements of ROS dynamics under UHDR conditions are challenging, making Monte Carlo simulations valuable complementary tools for tracking individual water radiolysis species over time.


Purpose
To enable a mechanistic investigation of ROS yield reductions under UHDR conditions, we developed a GPU‐based water radiolysis simulation platform capable of modeling key radiation chemistry processes.


Methods

Using our MPEXS2.1‐DNA framework with step‐by‐step molecular tracking, we simulated sequential 55 MeV proton irradiation in a 1 × 1 × 1 µm
3
target volume within a 2 × 2 × 2 µm
3
water phantom filled with neutral pH water at dose rates ranging from 0.02 Gy/s to 500 Gy/s, with a total absorbed dose of 10 Gy. Simulations were performed under oxygenated (pO
2
 = 25%, 239.4 µM) and deoxygenated (pO
2
 = 0%) conditions without additional scavengers. Radiation chemical yields (G values, species/100 eV) of hydroxyl radicals, hydrated electrons, and hydrogen peroxide were calculated at time points from 1 ms to 1000 s post‐irradiation. Statistical analysis was performed using 1000 independent sequential proton irradiation scenarios per dose rate condition, processed in parallel on a single GPU. Results were compared with published experimental data.



Results
The calculated dose rate dependence of the G values of hydroxyl radicals showed agreement with experimental data, with relative G values decreasing monotonically from 1.0 at 0.02 Gy/s to approximately 0.12 at 500 Gy/s at 10 ms post‐irradiation. Our simulations revealed that intertrack chemical reactions between neighboring proton tracks occurred, leading to decreases in the G values of hydroxyl radicals through enhanced radical‐radical interactions. The G values of hydrated electrons remained constant (G ≈ 2.5 species/100 eV) across all dose rates under deoxygenated conditions, consistent with experimental observations. Oxygen consumption followed a depletion rate of 0.028%/Gy (0.27 µM/Gy), in agreement with experimental measurements, but was insufficient to cause significant depletion at typical UHDR doses (10–40 Gy). Additionally, the calculated G values of hydrogen peroxide increased by 20% with dose rate (contrary to measured decreases of 20%–40%), suggesting the presence of competitive reaction pathways not included in current models.


Conclusions
We developed a GPU‐based computational framework for water radiolysis simulations under UHDR conditions using MPEXS2.1‐DNA. Our step‐by‐step approach enabled spatially precise tracking of intertrack reactions among radiolysis species originating from different proton tracks, a capability not achievable with conventional simplified methods. Additionally, we demonstrated that large‐scale statistical analysis is computationally feasible under UHDR conditions through GPU acceleration. Our results successfully reproduced the experimental trends for the G values of hydroxyl radicals and hydrated electrons. Oxygen depletion rates also showed good agreement with experimental measurements. However, the discrepancy between simulated and measured G values of hydrogen peroxide indicates the need to incorporate additional competitive reactions, potentially including third‐order mechanisms, for future UHDR modeling studies.