3D Imaging of Proton FLASH Radiation Using a Multi-Detector Small Animal PET System

<b>Objectives:</b> Ultra-high dose-rate FLASH radiotherapy has demonstrated strong potential in reducing normal tissue toxicity while maintaining effective tumor control. However, its underlying radiobiological mechanisms remain unclear, highlighting the need for novel approaches to probe the effects of radiation during and immediately after delivery. This study presents the first exploration of 3D PET imaging of positron-emitting nuclei (PENs) generated by a FLASH proton beam. <b>Methods:</b> A home-built 12-panel preclinical small-animal PET system was employed for recording coincidence events. A 142.4 MeV FLASH proton beam with a 100 ms delivery time was directed into a solid water phantom. PET coincidence signals were recorded during the first 1 s and up to 11 min. The system's capability for 3D localization was also assessed, and Monte Carlo simulations were performed for validation. <b>Results:</b> The PET system successfully recorded coincidence data within the first second, including the 100 ms beam delivery interval. Detector dead-time effects under the high beam flux were observed, leading to underestimated event counts. Following irradiation, the measured activity and decay behavior were consistent with simulations. The PET system accurately reconstructed the spatial distribution of PEN activities, with discrepancies in measured versus calculated line profiles ranging from 3.35-6.85%. Reconstructed PET images enabled reliable 3D localization with sub-millimeter accuracy in both lateral and depth dimensions. <b>Conclusions:</b> Our findings demonstrate that a multi-detector PET system is a promising tool for investigating the radiation effects of FLASH beams.