Project Summary/Abstract Support is requested to purchase the Xstrahl Small Animal Radiation Research Platform (SARRP) which would become the only image-guided small animal radiation delivery machine in the state of Alabama and would dramatically enhance the preclinical research and translational potential at The University of Alabama at Birmingham (UAB). Currently, there are 3 cabinet irradiators designated for animal and in vitro use on campus at UAB and are utilized by ~500 users. However, none of these have image guidance or focal irradiation potential. Indeed, irradiation is delivered using square field design and targets large tissue regions requiring lead blocks for shielding animals from undesirable radiation. This is especially problematic for the large number of investigators who rely on organ-specific radiation targeting such as orthotopically implanted cancer xenografts, radiation-injury models, and similar models. Moreover, many investigators rely on advanced small animal imaging modalities including CT, MRI, PET and luminescence to non-invasively monitor tumors over time though these datasets cannot be used for radiation treatment planning due to lack of image guidance in our existing cabinet irradiators which are the preclinical equivalent of clinical radiation oncology from 50 years ago. This scenario is in stark contrast the UAB department of radiation oncology which is a world leader in clinical radiation treatment delivery having been part of many “firsts” including first clinical use of Varian RapidArc (volumetric modulated arc therapy), first intrafraction motion review (“triggered imaging”) for lung cancer radiosurgery in the world, first adaptive Varian Ethos radiation, first North American treatment using Varian HyperArc (Automated multiple target radiosurgery optimization and delivery) co-developed by UAB, and first program in the United States to use Varian Edge radiosurgery with virtual cone delivery to treat movement disorder patients (e.g., essential tremor or tremor-dominant Parkinson’s patients). The acquisition of the SARRP would provide true clinical beam delivery geometry with non-coplanar beam arrangements, dynamic motorized variable collimator to adjust down to as small as 2 mm x 2mm field size, comprehensive animal positioning in virtually any orientation with on-board cone beam computed tomography (CBCT), and advanced image fusion from external imaging modalities such as bioluminescence, MRI and PET to enable precisely focused radiation with image guided accuracy. These capabilities are in demand at UAB yet remain unavailable. Therefore, the UAB School of Medicine and the O’Neal Comprehensive Cancer Center are committed to supporting this S10 proposal by providing assurances for sustained success of the SARRP as part of our successful Small Animal Imaging Core which will support ongoing projects and foster new ones for our research community.