Volumetric FLASH dosimetry <i>in vivo</i> using real-time radiacoustic imaging

OBJECTIVE: The main goal of this research is to verify the spatial fidelity of Radiacoustic Imaging (RAI) as a quantitative dosimetric monitoring tool for FLASH radiotherapy (FLASH-RT) in vivo. FLASH-RT delivers therapeutic radiation at ultra-high dose rates (>10 6 Gy/s), offering substantial reductions in normal tissue toxicity while maintaining tumor control. However, clinical translation remains limited by the absence of real-time, in vivo dosimetry systems capable of resolving dose delivery at microsecond timescales. APPROACH: Here, we present an RAI platform that enables volumetric, single-pulse mapping of radiation dose deposition during FLASH-RT in vivo. The system utilizes a 16×16 ultrasound transducer matrix array with a model-based reconstruction algorithm to generate quantitative, three-dimensional dose maps with single pulse-level temporal resolution. MAIN RESULTS: In both water phantoms and in vivo murine models, RAI demonstrates high concordance with film dosimetry and TOPAS Monte Carlo simulations (3%/3mm gamma index pass rates greater than 90%). SIGNIFICANCE: This work establishes RAI as a viable technology for real-time, quantitative electron FLASH dosimetry in vivo for the first time, with the potential to support adaptive delivery, improve treatment safety, and facilitate the clinical translation of FLASH-RT.