The Biophysics of Flash Radiotherapy: Tools for Measuring Tumor and Normal Tissues Microenvironment.

Ultra-high dose rate radiotherapy known as Flash radiotherapy (FLASH-RT) offers tremendous opportunities to improve the therapeutic ratio of radiotherapy by sparing the normal tissue while maintaining similar tumoricidal efficacy. However, the underlying biophysical basis of the FLASH effect remains under active investigation with several proposed mechanisms involving oxygen depletion, altered free-radical chemistry, and differential biological responses. This article provides an overview of available experimental and computational tools that can be utilized to probe the tumor and normal tissue microenvironment. We analyze in vitro, ex vivo, and in vivo systems used to study FLASH responses. We describe various computational and imaging technologies that can potentially aid in understanding the biophysics of FLASH-RT and lead to safer clinical translational.