ABSTRACT (OVERALL) The long-term goal of this NCBIB is to establish a national resource for enabling UHF (7T and above) magnetic resonance imaging (MRI) technologies to advance biomedical research and discovery. We propose to build on our successes in this renewal with four new closely linked technical research and development (TRD) projects. These projects will work synergistically to realize the potential of our unique imaging resources which include our 10.5 Tesla (currently the highest magnetic field available for human and large non-human primate (NHP) imagining above 10T), and 16.4 Tesla for small to medium size animal models (one of two such high fields systems in the world). TRD1 will undertake the development of a multimodal imaging with simultaneous MR and novel electrodes and augment its current effort on large NHPs with a small NHP model, namely the marmosets, for use in 16.4T MR and multiphoton optical imaging studies. The combination of non-invasive MR and an invasive technology will provide access to neuronal activity from single neuron and synapse level over the entire brain but at a coarser spatiotemporal resolution. This platform will provide opportunities for detailed studies of brain function in NHP models and inform future human studies using MRI alone. TRD2 will develop new MR contrasts and novel technologies for ultrahigh field applications, with a specific focus on selected technologies that will have the greatest impact on associated collaborative and service projects. The effort will provide unparalleled sensitivity to probe molecular and physiological parameters to characterize tissue, support biomedical research and impact our understanding of the living system in health and disease. TRD3 has been at the forefront of image reconstruction technologies, introducing multiple new methods for improved Deep Learning (DL) reconstruction and training, interpretable image denoising, and fast iterative algorithms. TRD3 will continue to tackle inverse problems through the lens of intelligent physics-driven technologies that synergistically utilize imaging physics and advances in DL methods targeting target higher resolutions and acceleration rates at lower signal-to-noise ratios (SNR), as well as to combine information across multiple nuclei or even modalities. TRD4 provides critical engineering solutions addressing both radiofrequency (RF) coil (i.e. antennae) designs and safety, towards capturing the significantly higher ultimate intrinsic SNR (uiSNR) provided by UHF. The effort will employ novel RF electronics concepts including miniaturized integrated circuit low noise amplifiers and coil clusters and explore new receiver concepts both for multinuclear and 1H imaging and spectroscopy studies at the high magnetic fields of 10.5T, 7T and 16.4T. While the focus is on uniquely high magnetic fields, the impact of this Center on biomedical research will extend to lower magnetic fields, as it has done so already, as well as to fields beyond MRI (cognitive science, neuroscience, senescence, musculoskeletal disorders, neurological disorder, cancer among others).

PROJECT NARRATIVE (OVERALL) This biotechnology research center project establishes a national resource that will provide cutting edge technologies to enable the use of magnetic resonance imaging (MRI) devices running at ultrahigh magnetic fields of 10.5T and 16.4T as sensitive tools for basic and clinical research. Combining these unique MRI capabilities with non-MR methods of advanced electrophysiology and multiphoton optical imaging system, a first of its kind, will be used to provide novel insights into brain function and connectivity from single neurons to the whole brain. Clinical research will benefit from the development of advanced methods that report on physiological and molecular processes where UHF will provide increased sensitivity assessing disease progression and evaluating treatment response. Specific engineering, physics and image reconstruction strategies will be implemented to realize the full potential of UHF systems.