NIH Merit Award (R37) extension request-R37CA240806, Xiang, (Shawn) Liangzhong The Overall Objective of this application is to enable in vivo dosimetry during radiation therapy in cancer patient to the end-user– the medical physicist. Our Hypothesis is that X-ray-induced Acoustic Computed tomography (XACT) can be used for 4D in vivo dosimetry in patients. In XACT, pulsed x-rays are absorbed and converted to heat. The resulting thermoelastic expansion generates a 3D acoustic wave, which can be detected by acoustic detectors to form images. The amplitude of the acoustic waves is proportional to X-ray absorption, and therefore encodes dose information. Our overall strategy is to design/construct a 3D XACT dosimetric scanner, and to test/refine the imaging prototype under clinical conditions based on an Academic-Industrial partnership among University of California, Irvine (UCI), University of Oklahoma Health Sciences Center (OUHSC), and PhotoSound Technologies Inc. Our original specific aims in year 1-5 are: (Specific aim 1) Evaluate the basis of the XACT imaging in radiotherapy dosimetry; (Specific aim 2) Develop a 3D XACT imaging system for clinical implementation; and (Specific aim 3) Validate the performance of XACT under clinical conditions. For year 6&7, we propose to develop dual-modal XACT/US imaging system that combines both XACT and pulse-echo ultrasound imaging. It can be used for 1) real-time monitoring the misalignment between the targeted tumor and the delivered radiation beam during radiotherapy, and 2) quantitative dose measurement in vivo, which will push the current paradigm to high-precision radiotherapy. This discovery is the first time in history that radiation dose in tissue could be directly visualized with high spatial and temporal resolution. If successful, the ability to localize the radiation beam and map the radiation dose will enable a paradigm shift towards high-precision radiotherapy.