Transgenic rodents are the most important translational model for studying pathogenesis and treatment of disease. However magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as spectroscopic imaging (MRSI) studies of transgenic mouse and recently transgenic rat have been limited due to not having sufficient spatial resolution to distinguish key anatomic structures such as cortical columns and layers. With development of ultrahigh field (UHF) animal MR systems, using cryogenic technology for sensitivity enhancement, there is unique opportunity to break this sensitivity barrier allowing ultrahigh resolution functional, structural, and metabolic 3D brain imaging in transgenic models, with a direct path to translation to human studies. The primary goal of this proposal is to install and develop capabilities of a state-of-the-art UHF Bruker 11.7T/16cm preclinical scanner with cryoprobes for 1H and X nuclei at Yale's Magnetic Resonance Research Center (MRRC) for ultrahigh resolution functional, structural, and metabolic imaging in small animals, fixed tissues, and human organoids. Our primary Justification of Need is that this new system will replace an unsupported 20-year old 11.7T pumped magnet with extremely high helium costs that is close to failure. The new 11.7T system will allow our outstanding userbase, and investigators throughout the NIH community, to continue their funded research on a reliable state-of-the-art system, and obtain several-fold sensitivity gains for multi-modal MRI/MRSI via cryogenic coil technology and to answer cutting edge basic and translational neuroscience research questions. The system will be managed by a team of MRI/MRSI researchers with outstanding Technical Expertise and decades of track record in operating and developing UHF systems for MRI/MRSI studies. We have identified 14 Major Users with 18 NIH Research Projects that will most benefit from the new system along with 8 Minor Users. Several are from peer institutions who are performing their preclinical MRI/MRSI projects at Yale MRRC due to our unique method developments. The Administration plan builds on our 35-year experience in facility management, with highly experienced operations, steering, and advisory committees with leading intramural and extramural researchers. Yale University will provide a substantial Institutional Commitment totaling $2,100,000 in matching funds towards the system's cost and pay for complete installation. The system will also benefit Trainee Education based on participation of many of the core MR faculty in mentoring of graduate students and post-doctoral fellows, as well as classroom teaching. By combining UHF with superior gradient performance and cryoprobes for 1H and X nuclei we anticipate an approximately 2.5- to 4-fold gain in sensitivity over our existing unsupported 11.7T system. These improvements will allow translation of our multinuclear and multimodal MRI/MRSI to studies of the transgenic mouse brain and ultrahigh resolution rat brain studies. Thus, the requested 11.7T will fulfill urgent needs for state-of-the-art MRI/MRSI research for NIH-funded investigators at Yale, and elsewhere.

This application requests funds to purchase and install a state-of-the-art 11.7T/16cm small bore animal MRI scanner with cryoprobes for 1H and X nuclei at Yale University with a substantial institutional match. This novel equipment will greatly enhance the small animal MRI research capabilities of a highly productive MRI research community, including scientists from Yale and elsewhere, spanning across disciplines of neuroscience, metabolism, cancer, physiology, physics, and engineering.