Brian Rutt - US grants

DESCRIPTION (provided by applicant): The long-term objective of this Shared Instrumentation Grant application is to bring to the research community at Stanford a next-generation 7 Tesla whole-body magnetic resonance imaging (MRI) system, specifically the GE Discover MR950 7.0T system with parallel transmit capabilities, to serve as a platform for cutting-edge imaging technology research and development, as well as for radiological and neuroscience research. The approach we describe in this proposal is interdisciplinary, bringing together researchers from the specialties of physics, engineering, bioengineering, biology, physiology, radiology, neurology, psychiatry, and psychology. The shared instrumentation requested here will act as a catalyst and common platform for this group to create, refine, implement, validate and utilize the most advanced forms of magnetic resonance imaging. Major patient-based imaging research applications of the next-generation 7T MRI platform include studies of brain development, psychopathology, drug dependence, alcohol-induced brain damage and its functional consequences, neurodegenerative processes, Williams, Turner and fragile X syndromes, brain injury, breast cancer, joint injuries, and therapeutic interventions associated with some or all of the above. Major technology development directions that will be enabled by this next-generation 7T MRI platform include MR spectroscopic imaging (MRSI) of the proton (1H) nucleus as well as non-proton nuclei, in both brain and musculoskeletal systems, advanced perfusion and diffusion tensor imaging in brain, whole breast imaging, and, importantly, parallel transmit technology for mitigating B1 inhomogeneities that limit the use of high magnetic field MRI in any organ system. The overarching aims of the proposed research are to develop software and hardware methods to allow 7T MRI to have a much greater impact on clinical research than possible before, as well as to extend the capabilities of high-field MRI to unprecedented levels of spatial resolution, metabolite and iron sensitivity, and tissue characterization. The proposed research projects are highly compatible with the mission of the Department of Health and Human Services and relevant to public health. The proposed research will take place at interdisciplinary laboratories directed by international leaders in imaging research: high field and high sensitivity MRI methodology development (Dr. Brian Rutt, PI), developmental disorders and clinical neuroscience (Dr. Allan Reiss), DTI methodology development (Dr. Roland Bammer), musculoskeletal disorders and radiological research (Dr. Garry Gold), breast MRI methodology development (Dr. Brian Hargreaves), parallel transmit and RF pulse technology development (Dr. John Pauly), psychiatric disorders and neuroimaging (Drs. Dolf Pfefferbaum and Edith Sullivan), MR spectroscopic imaging methodology development (Dr. Dan Spielman), psychiatric disorders and clinical neuroscience (Dr. Edith Sullivan), cognitive neuroscience and neuroimaging (Dr. Brian Wandell) and neurovascular imaging (Dr. Greg Zaharchuk). Project Narrative / Relevance: Disorders of brain development and function (both early and late in life), breast cancer and joint injuries/pain are three disparate pathologies that affect billions of people worldwide. The placement of a next generation, human 7T MRI system to Stanford will provide a platform for significant expansion of not just MRI methodology development, but also both basic biological as well as clinical research, all of which promise to contribute substantively to our institution's long-term goals for improving the health and well being of individuals suffering from these disorders.

Project Summary A complete understanding of both normal brain function and neurological disorders / mental illness will require the deciphering of the complex brain networks that underlie behavior and cognition, at both whole-brain and microscopic scales. The difficulty of structurally and functionally mapping these brain networks in living human subjects with sufficient sensitivity and resolution to understand normal function and detect pathological change represents a fundamental challenge. Recognizing these challenges, the NIH and other funding agencies have supported new initiatives in brain mapping for decades, starting with the Decade of the Brain, followed by the Decade after the Decade of the Brain, the New Century of the Brain, the Human Connectome Project, and most recently the BRAIN Initiative. Most of these brain mapping initiatives have featured MRI, the premier tool for studying the intact living human brain, non-invasively, at high resolution, and with high sensitivity to many subtle physiological and pathological processes. For example, the NIH-funded Human Connectome Project (HCP) was launched in 2009 to comprehensively map brain circuitry in 1,200 healthy subjects using MRI, and has already had a large impact on the neuroscience field. The HCP uses diffusion MRI (dMRI) and BOLD-based functional MRI (fMRI) to derive whole-brain structural and functional connectivity maps for individual subjects at 1.25-2mm resolution (2-8µL voxels). Such coarse resolution results in the spatial blurring of single-voxel responses over 105-106 neurons. The NIH BRAIN Initiative calls for disruptive new approaches to resolving brain circuit connections and function at dramatically higher spatiotemporal and microstructure resolution. This 2-year proof-of-concept BRAIN R01 will focus on producing a complete and validated design for a next-generation, compact, low-cost, high-performance ultra-high-field (UHF) MRI system, capable of resolving neural connections and circuitry at the scale of 104 neurons (~0.2µL), throughout the entire living human brain non-invasively. This would address a specific target identified in BRAIN 2025, which calls for significant developments in MR methodology targeting whole brain studies with voxel volumes of 0.3-0.4µL in the short term, and 0.1µL or better in the long term. Our specific goals in this project are to re- engineer all front-end hardware components of the UHF MRI system, thereby resolving the technological and physics challenges that have been severely holding back this human brain imaging modality. We will develop several disruptive technologies, designed synergistically to create a dramatically lower cost but higher performing UHF MRI system: 1) ultra-compact UHF magnet technology; 2) ultra-high-performance gradient hardware; and 3) innovative shim and RF array technologies designed to fully correct both main field and RF inhomogeneity problems. The practical impact of our work will be to enable greatly improved human brain mapping using dMRI and fMRI, while simultaneously solving the major technological and cost limitations of UHF MRI.