Summary This high-end shared instrument grant proposal is to replace the existing hybrid SPECT/CT scanner (Discovery NMCT570c, GE Healthcare) that was purchased in 2010 with a shared instrumentation grant (1 S10 RR025555-01) entitled, “Hybrid Volumetric SPECT/CT Imaging System”, with a new SPECT/CT that has 12 cadmium zinc telluride (CZT) detector modules in a unique 360° configuration with adaptable detector position and angle. This new CZT-based SPECT technology is capable of focused or whole-body imaging and will be applied for radionuclide targeted molecular imaging in larger animals in evaluation of a wide variety of diseases. The new CZT detector system will provide improved sensitivity and spatial resolution, bringing the SPECT technology closer to that of PET. The proposed hybrid scanner will facilitate correction for errors attributed to attenuation, scatter, partial volume effects, and radiotracer crosstalk during dual isotope acquisitions facilitating quantitative SPECT radiotracer-based molecular imaging. The high sensitivity of the technology will also enable ultra-fast dynamic SPECT imaging, which should prove to be extremely valuable for determining the biokinetics of new targeted radiotracers and allows for the determination of absolute blood flow through established kinetic modeling approaches. The high sensitivity also allows for shorter scan times as well as respiratory and cardiac gating which will minimize the possibility of subject and/or cardiac motion and therefore reduce motion related artifacts. The proposed system will enhance our established translational facilities for imaging of both small and large animals, human cadavers, and facilitate translational research at our institution. The CZT-based SPECT/CT imaging system will support the needs of multiple current NIH funded investigators at Yale University School of Medicine, from the Departments of Internal Medicine, Radiology & Biomedical Imaging, Surgery, and from the Department of Biomedical Engineering at Yale University as well as investigators at multiple other academic institutions throughout the US. The user group works on a variety of projects, which would utilize different features of the proposed equipment. The upgraded hybrid SPECT/CT imaging system will become an integral part of the Yale Translational Imaging Center (Y- TRIC), which has co-located large animal holding and surgery facilities with state-of-the-art imaging resources for translational animal research. This center will nicely complement our current Yale Center for Clinical Investigation (YCCI), which has been repeatedly funded by an NIH CTSA grant for establishing an integrated environment for clinical and translational research. Funds will be available through the YCCI to fund pilot projects from new investigators to assure expanded utilization of the system.