Project Summary We propose to purchase a new Cubresa MRI-Compatible PET insert to be combined with our existing 9.4T Bruker Biospec preclinical MRI scanner at Case Western Reserve University (CWRU). This new PET insert will create the first preclinical PET-MRI capability in Cleveland that will efficiently synergize our extensive preclinical PET and MRI imaging research programs to support 25 major users with research in the areas of PET and MRI technology developments, molecular imaging agents, new gene editing strategies, metabolism, inflammation, and immunology. With this new PET-MRI capability, these investigators will be able to combine the unmatched sensitivity of 3D PET imaging with the high spatial resolution and wide range of selectable soft tissue contrasts provided by MRI. The proposed system will also result in significantly reduced imaging costs and inherent 3D PET-MRI image co-registration in comparison to sequential PET-CT and MRI. The proposed system will also include: 1) PET- optimized radiofrequency coils enabling high-sensitivity MRI signal detection; 2) respiratory gating to limit motion artifacts; 3) multiple VivoQuant software licenses to provide efficient image visualization and analysis; and 4) physiologic monitoring and control capabilities necessary for effective metabolic imaging studies. These capabilities will broadly benefit an interdisciplinary group of investigators with the ultimate goal of improving health care for patients with cancer, genetic diseases including cystic fibrosis, inflammatory bowel disease, neurodegenerative diseases such as Alzheimer’s Disease and multiple sclerosis, cardiovascular disease, diabetes, and stroke. This new preclinical PET-MRI capability will be available to all regional investigators and will be operated by the Imaging Research Core at CWRU which is an integral component of multiple research centers at CWRU including the Case Comprehensive Cancer Center (NCI P30 CA043703), the Digestive Diseases Research Core Center (NIDDK P30 DK097948), the Clinical and Translational Science Collaborative (NCATS UL1 TR002548), and the Cystic Fibrosis Research Center. This ongoing support for the Imaging Research Core is in addition to the direct institutional support of $100,000 to partially offset the cost for this new PET imaging insert. An advisory committee with highly experienced PET and MRI faculty at CWRU and external institutions will oversee the organization and usage of the system and recommend policies to maintain system performance and maximize utilization.