Differential tissue sparing of FLASH ultra high dose rates: an {\it in-silico} study

TL;DR

This study models how tissue structural complexity influences the differential sparing effects of FLASH ultra high dose rate radiotherapy, suggesting that cellular heterogeneity affects chemical interactions and tissue response.

Contribution

It introduces a reaction-diffusion model on a random network to explain tissue-specific effects of FLASH radiotherapy based on structural complexity.

Findings

Normal tissue exhibits interconnected track networks facilitating chemical reactions.

Tumor tissue shows isolated tracks with minimal interaction, leading to differential sparing.

Structural complexity correlates with the extent of tissue sparing in FLASH UHDR.

Abstract

Purpose: To propose a theory for the differential tissue sparing of FLASH ultra high dose rates (UHDR) through inter-track reaction-diffusion mechanism. Methods: We calculate the time-evolution of particle track-structures using a system of coupled reaction-diffusion equations on a random network designed for molecular transport in porous and disordered media. The network is representative of the intra- and inter-cellular diffusion channels in tissues. Spatial cellular heterogeneities over the scale of track spacing have been constructed by incorporating random fluctuations in the connectivity among network sites. Results: We demonstrate the occurrence of phase separation among the tracks as the complexity in intra- and inter-cellular structural increases. At the weak limit of disorder, such as in water and normal tissue, neighboring tracks melt into each other and form a percolated network of nonreactive species. In contrast, at the strong limit of disorder, tracks evolve individually like isolated islands with negligible inter-track overlap. Thus, the spatio-temporal correlation among the chemical domains decreases as the inter-cellular complexity of the tissue increases (e.g. from normal tissue to fractal-type malignant tissue). Conclusions: The differential sparing of FLASH UHDR in normal and tumor tissue may be explained by differences in inter- and intra-cellular structural complexities between the tissue types. The structural complexities of cancerous cells prevent clustering and chemical interaction of tracks, whereas this interaction prevails and thus leads to sparing in normal tissue.