Project Summary/Abstract This application seeks support from NIMH to purchase the 3-Tesla magnetic resonance (MR)-compatible positron emission tomography (PET) brain scanner manufactured by Cubresa, Inc. PET and MRI are two of the most powerful imaging modalities currently in use for studying the human brain. Scanners capable of simultaneous PET and MR whole-body data acquisition in human subjects became commercially available a decade ago. However, until recently, there was no equivalent dedicated head device on the market to address the needs of the researchers and clinicians focusing on the brain and the performance of whole-body devices is rather limited for this purpose. A high-performance MR-compatible BrainPET scanner installed at the Martinos Center would benefit many brain-focused research studies in our center and in the community. The Cubresa BrainPET would replace the Siemens BrainPET prototype that was installed at the Martinos Center in May 2008 and has served our investigators effectively for more than a decade. It was moved in the Martinos Center PET & Radiochemistry Facility in June 2011 and became the workhorse of our PET program for many years even after the installation of the Biograph mMR. At peak usage, three-dozen projects were using the BrainPET prototype in a variety of studies ranging from those aimed at characterizing the scanner performance, developing methods to use the information obtained from one device to improve the other modality, and demonstrating the tremendous potential of this technology through proof-of-principle studies in non-human primates, healthy volunteers, and numerous patient populations. However, with the exceedingly fast PET detector developments seen in the last decade, the 15+ year old technology has now become outdated. The service agreement for the BrainPET prototype ended 5 years ago and the prototype has been non-functional for about a third of 2021 due to technical failures. Therefore, a replacement of this aging and obsolete system will be necessary to enhance and complete the scientific goals and aims of the ongoing projects focused on several mental disorders and related topics (i.e., anxiety disorders, autism spectrum disorder, bipolar disorder, depression, HIV/AIDS and mental health, schizophrenia, substance use, traumatic events) as well as on neurological diseases and basic neuroscience. The installation of the new instrument is being supported by the MGH leadership, Radiology Department, and Martinos Center. This multi-level institutional support covers allocation of instrument space and assistance for installation, operational support in terms of system scheduling, accounting, and maintenance, and lastly, a commitment of up to $278,000 to cover the gap between the NIH SIG award and the purchasing price for the upgrade, in addition to the committed funds of $100,000 from the MGH Executive Committee for Research. Following the installation, the Cubresa BrainPET will be managed by the...