3D In vivo dosimetry for FLASH proton therapy

ABSTRACT: This U01 application aims to (1) develop a robust protoacoustic dosimeter for 3D in vivo dosimetry in proton FLASH therapy, which is essential for its clinical application and acceptance; (2) form a multi-disciplinary and multi-institutional research partnership, incorporating both academic and industrial entities, to hasten the

creation and implementation of this innovative dosimeter for clinical usage in the ensuing 5-10-years. More than half of cancer patients receive radiation therapy (RT) in their treatment journey. The recent RT method, FLASH, using an ultra-high dose rate, is noted for its ability to minimize normal tissue damage while maintaining

tumor control. Proton therapy is emerging as a promising delivery method for FLASH. Ensuring the precision of

proton FLASH delivery is critical given the high risks of such treatments. Errors in ultra-fast delivery can significantly affect dose delivery to the tumor and healthy tissues. As a result, there's an urgent need for a 3D in vivo dosimeter for validation and guidance of the actual dose delivered by FLASH. This necessity stems from the fact that current

dosimeters can't handle the ultra-high dose rate in FLASH or lack in vivo volumetric data. Thus, developing 3D in vivo dosimetry is key for the precise delivery of proton FLASH RT. Our proposal involves the creation of a novel Protoacoustic/Ultrasound Dual-modality Imaging System (PUDIS) to meet this pressing need. PUDIS uses protoacoustic imaging for dosimetry validation, and we are pioneers in

exploring radiation-induced acoustic imaging for radiation dosimetry. Recently, we've shown the potential of using protoacoustic signals for in vivo dosimetry of a single proton pulse. However, more work is needed to explore this technology under FLASH dose rate and significantly enhance the image quality for precise 3D dosimetry.

We aim to accomplish this through the following objectives: Aim 1: Characterize the basis of protoacoustic imaging as a FLASH dosimeter on human-size phantom. Aim 2: Develop a robust protoacoustic/ultrasound dual-modality imaging system (PUDIS) for dosimetry/anatomy verification on animal models in vivo. Aim 3: Establish PUDIS as

a quantitative 3D dosimetry system for FLASH therapy. Outcome/Impact: This grant will result in a rigorously vetted PUDIS prototype, marking the first introduction of 3D in vivo dosimetry to proton FLASH RT. Backed by a team of cross-institutional academic and industry experts, we anticipate a successful project. PUDIS's in vivo 3D dose verification will catalyze precise proton FLASH RT,

unlocking FLASH's full potential. This accelerates research, application, and acceptance of this treatment, ultimately benefiting cancer patients vulnerable to RT-related toxicities.