PROJECT SUMMARY/ABSTRACT Pathological changes in the human metabolome are ubiquitous and fundamental to the pathogenesis of all brain disorders including cancer, dementia, and psychiatric disorders. This project proposes to develop a non-invasive magnetic resonance imaging tool to interrogate human brain metabolism in an unprecedented way using the world’s first ultra-high field 10.5 T whole-body human MRI scanner and a novel dynamic deuterium to proton exchange (2H-to-1H) MRS approach. Two complimentary strategies, single-voxel spectroscopy (SVS) and MR spectroscopic imaging (MRSI) will be developed in parallel. 2H-to-1H MRS will be able to quantify and image concentrations and metabolic fluxes in the human brain in vivo through the entire metabolic pathway from a single scan. In the first part of this project, we will utilize state-of-the-art MR-compatible sensors and calibration scans to accurately characterize spatial field inhomogeneities and monitor scanner- and subject-dependent temporal instabilities at 10.5 T. In the second part, we will develop and validate a novel dynamic 1H-SVS technique at 10.5 T with the focus on maximizing the range of reproducibly detectable metabolites by targeting a single accurately defined brain region. In the third part, we will establish a new highly accurate and robust dynamic 1H-MRSI method for 10.5 T, which will trade-off the ability to interrogate a broad range of metabolites for the ability to image some of them over the entire brain. In the final part, we will proof the feasibility of measuring human brain metabolism in vivo non-invasively via dynamic 2H-to-1H MRS at 10.5 T and 7 T using 2H-labled glucose and estimate experimental and physiologic variability. We will compare the performance of our novel tool to deuterium metabolic imaging. Successful completion of this project will provide a powerful tool for neuroscience and metabolic research.

PROJECT NARRATIVE Magnetic resonance spectroscopy (MRS) can provide metabolic concentration noninvasively in the human brain. The tools for measuring metabolism are very limited. This research project will develop and evaluate the tools, which would allow the robust measurement of both metabolic concentrations and metabolic rates in the human brain.