Purpose: To investigate the contribution of interspur interactions (interactions between radiolytic species of individual particle tracks) to overall radiochemical interactions as a function of irradiation and target parameters. We hypothesize that an increase in interspur interaction is responsible for the observed normal tissue sparing in FLASH-RT.
Methods: We construct a model that analytically represents the spatiotemporal distribution of spurs in a water target as a function of irradiation parameters (e.g. dose, dose rate, LET), and quantifies the effect of interspur interactions on the ongoing radiochemistry. Spurs are modeled by exponentially decaying normal distributions based on Monte Carlo simulations, and interspur interaction is quantified by the expectation value of interspur overlap in the target. The spur decay rate, a tissue-dependent model parameter, represents the species-consuming effect of intraspur and spur-environment interactions.
Results: The contribution of interspur interactions is given as a function of irradiation and tissue parameters. For any set of parameters, a minimum critical dose and dose rate are determined to induce majority interspur interaction (MII). Interspur interactions are directly proportional to the particle flux, and thus indirectly proportional to the beam LET at a fixed dose. An increasing spur decay rate raises the minimum critical dose and dose rate for MII. The time scale of the onset of MII for a given set of irradiation parameters as predicted by the model agrees well with Monte Carlo simulations.
Conclusion: The as-yet undetermined mechanism of the FLASH effect may be caused by interspur interaction induced by the high doses and dose rates characteristic of FLASH irradiation. The analytical model provides a simple method to test this hypothesis by predicting the irradiation parameters necessary to induce interspur interactions.
TH- Radiobiology(RBio)/Biology(Bio): RBio- LQ/TCP/NTCP/outcome modeling