Project Summary/Abstract Stereotactic body radiation therapy (SBRT) is one of the most effective, well-tolerated, and cost-effective treatments. The success of SBRT relies heavily on the precision of dose delivery, due to the typically small tumor size, the very high radiation dose per fraction, and the sharp dose fall-off outside the target. For those sites where the tumor moves due to respiration, motion management is indispensable to ensure the high-precision dose delivery of SBRT. Current motion management strategies are either treating a large area encompassing the tumor motion range, or only delivering radiation dose within a small window (e.g., a gating window or at the end of inhale) of tumor motion cycle via indirect and inferior tumor motion monitoring (such as external surrogates or implanted fiducial markers). In-treatment real-time volumetric imaging is highly desired to enable direct, accurate, and markerless 3D tumor tracking for better motion management and capture unexpected large tumor motion for patient safety. The availability and accuracy of in-treatment real-time patient 3D anatomy information is also essential to the development of more active and advanced motion management technologies, such as multileaf collimator tracking and 4D treatment delivery. The unpredictable motion change during treatment can lead to substantial deviation of the delivered dose from the planned dose. Adaptive radiotherapy can compensate for the dosimetric errors by adapting the subsequent fractions. However, due to the notable changes of respiration, the pre-treatment imaging cannot provide the patient’s actual in-treatment anatomy to assess the actual delivered dose for adaptive radiotherapy. In-treatment real-time volumetric imaging is needed to enable dose-guided adaptive SBRT. Despite these strong needs, real-time volumetric imaging is not currently available due to the big challenge of reconstructing an instantaneous 3D image from very few 2D projections to meet the real-time requirement. To fill this clinical gap, we plan to develop a real-time volumetric imaging-based tumor tracking and dose verification (RITD) system using novel techniques in deep learning, imaging, Monte Carlo simulation and high-performance computation, and use lung SBRT treatment as a testbed. We will accomplish the following specific aims: 1) To develop and refine a real-time on-board volumetric imaging and tumor tracking method; 2) To develop an image correction method and a tumor/multi-organ segmentation method on the volumetric images; 3) To evaluate the performance of the proposed RITD system and assess its clinical benefit. The innovation of this study lies in developing new deep-learning approaches to enable real-time on-board volumetric imaging and build accurate tumor tracking and dose verification capability into cancer radiotherapy. It has substantial potential to improve lung SBRT treatment outcomes by reducing targeting uncertainty, improving treatment accu...