Establishing translational neuroimaging tools for quantitative assessment of energy metabolism and metabolic reprogramming in healthy and diseased human brain at 7T

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PROJECT SUMMARY Cellular energy metabolism is a fundamental process of life that produces biochemical energy in the form of adenosine triphosphate (ATP) to support neuronal activity and brain function. Glucose and oxygen are the main energy substrates of the brain and are metabolized through glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation pathways, constituting a neuroenergetic network that effectively regulates ATP production and homeostasis. ATP production and homeostasis are affected when brain states change, as signs of altered cerebral glucose and oxidative metabolism are commonly seen in aging, neurodegenerative diseases, psychiatric disorders, stroke and cancer. Despite the important roles of brain energy metabolism, metabolic alteration and reprogramming in health and disease, noninvasive neuroimaging tools capable of mapping and quantifying key features of neuroenergetic network in the human brain are still lacking. Over the past two decades, we have developed three ultrahigh-field (UHF) metabolic imaging techniques based on deuterium-2 (2H), oxygen-17 (17O), and phosphorus-31 (31P) magnetic resonance spectroscopy (MRSI) imaging capable of noninvasive and quantitative assessment of brain energy metabolism along major metabolic pathways. However, X-nuclear MRSI-based methods face severe challenges in translational applications due to low detection sensitivity and metabolite content, and prolonged scanning time. This project aims to develop and integrate multiple cutting-edge technologies to build next generation high- resolution, high-performance and translatable neuroimaging tools on an FDA-approved 7 Tesla clinical scanner for quantitatively imaging key metabolic rates and other essential neurophysiological parameters related to energy metabolism in healthy and diseased human brains. Three pilot studies are proposed to test and demonstrate the utility and feasibility of the novel neuro-metabolic imaging tools to quantitatively study neuroenergetics and metabolic reprogramming in brain activation, aging processes and brain tumors, aiming to understand their critical roles in brain function and disease. This project leverages the interdisciplinary expertise of an outstanding team leading in the research field, excellent imaging facilities and resources, and close collaboration among team members. The advanced neuroimaging tools established by this project is expected to have significant impact on changing the paradigm of neurometabolic imaging and energy metabolism research, and enable translational studies of human brain bioenergetics and metabolic reprogramming under physiopathological conditions.