Project Summary/Abstract Stereotactic Body Radiation Therapy (SBRT) is an aggressive, ablative local therapy that can be an effective treatment for many hard-to-treat tumors, such as pancreatic adenocarcinoma, non-small cell lung cancer, melanoma, and renal cell carcinoma. By delivering large, ablative doses of radiation in a small number of treatments, SBRT leads to significantly improved local control. However, there is a trade-off between delivering aggressive doses of radiation in the abdomen with SBRT and dose-limiting side-effects. A major problem is that the breathing-induced motion of the abdomen is erratic and unstable, rendering traditional methods of motion management ineffective. To enable safe and effective dose escalation for these tumors, we are proposing a novel imaging system that measures the position of fiducial markers implanted inside the patient. This system, called Coded Aperture Scatter Imaging (CASI), passively measures the position of tumors during treatment with no additional radiation dose. During radiotherapy, a beam of megavoltage x-rays is directed towards the tumor, and some of those photons undergo scattering interactions within the patient. These photons are more likely to interact in the dense, high-atomic-number fiducial markers, providing a differential signal that can be measured by an imager placed orthogonal to the beam. We propose to use coded aperture imaging to decode the location of these fiducial markers in real time. The coded aperture technique, utilized in fields such as astronomy and nuclear medicine, can help identify faint point sources within a broad background. CASI is clinically attractive for several reasons. This passive technique provides real-time motion information with no additional imaging dose, since it forms an image using scattered photons from the treatment beam. CASI is easily implementable on any existing clinical linear accelerator, since all modern linacs are equipped with a kV imaging panel placed orthogonal to the treatment beam. Fiducial markers are commonly implanted in these tumors, and the only additional hardware needed is the coded aperture itself, which can simply be placed between the patient and the detector. Finally, by measuring the motion of tumors during treatment one could increase the accuracy of treatment delivery, which could enable more effective, dose-escalated treatments that avoid toxicity to normal tissues. The goal of this work is to design, fabricate, and test an optimized aperture for CASI-guided radiotherapy.