Modeling the FLASH effect for ion beams using a microdosimetry-based model

Abstract

To develop a microdosimetry-informed modeling framework for predicting the ion-beam FLASH sparing effect (FSE) by coupling time-dependent oxygen depletion–recovery kinetics with oxygen-modulated radiosensitivity parameters, and to quantify how FSE varies with dose rate, oxygen tension, and beam quality (LET and dose-mean lineal energy, y¯D). Microdosimetric lineal energy spectra were calculated for various ion beams (proton, helium, lithium, beryllium, boron and carbon) utilizing GATE Monte Carlo software package. An analytical framework was developed that uses microdosimetric lineal-energy inputs (dose-mean lineal energy, y¯D) together with a time-dependent oxygen depletion–recovery model to modulate linear-quadratic (LQ) parameters ( α, β) as a function of oxygen tension during irradiation. The quantifications of the LQ parameter α, the FLASH sparing effect (FSE) and its dependence on the dose rate (0.1–1000 Gy s−1), dose-averaged lineal energy y¯D, oxygen concentration, ion species and radiosensitivity were then performed. The ion beam FLASH model based on microdosimetry is able to quantify the FLASH effect of different oxygen concentrations, dose rates, ion species, and radiosensitivities. The LQ parameter α shows a dependence on the oxygen concentration for all ion species with various dose rates and saturated at high-oxygen-concentration level. FSE increases with increasing environmental oxygen concentration while decreases after reaching the dose-rate-dependent maximum. The FSE increases with an increasing dose rate. With the increasing lineal energy transfer (LET) or y¯D, FSE increases and then decreases, and finally tends to approach unity in high LET or y¯D region. The FSE-LET relationship showed a dependence on ion species, especially at high LET region. This framework provides a quantitative link between ion-beam microdosimetric descriptors and oxygen-driven FLASH response, enabling systematic exploration of parameter regimes where sparing is predicted to be most pronounced. The model may support hypothesis testing and future integration into treatment-planning-oriented studies for ion-beam FLASH, while highlighting the importance of oxygen kinetics and beam-quality dependence.