A fundamental discovery of modern human brain imaging with positron emission tomography (PET) that blood flow to activated regions of the normal human brain increases substantially more than oxygen consumption has lead to a broad discussion in the literature concerning possible mechanisms responsible for this phenomenon. It is well known that oxygen delivery is not the only function of systemic circulation. Additional roles include delivery of nutrients and other required substances to the tissue, waste removal, and temperature regulation. Among these other functions, the role of regional cerebral blood flow in local brain temperature regulation has received scant attention. Heat in the brain is produced mostly due to oxidative metabolism. It is removed chiefly by blood flow. The balance between heat production and removal in resting state maintains brain temperature at a constant level. However, a local increase in the blood flow and metabolism during brain functional activity can locally destroy this balance and alter brain temperature in the region of functional activity and surrounding tissue. This is an important issue since temperature substantially changes (by about 8 percent per each degree of centigrade) rates of metabolic reactions, the affinity of hemoglobin for oxygen, and, consequently, may affect brain performance - both healthy and diseased. This proposal seeks to provide data extending our understanding of the relationship between physiologic and metabolic control in nervous system. The major goals of this grant application are: To develop MR techniques that allow simultaneous monitoring of changes in brain temperature and oxidative metabolism. The proposed work includes implementations of MR techniques, development of biophysical models of brain temperature regulation and mathematical algorithms based on Bayesian probability theory for data processing. To measure by means of MR the spatial distribution in the changes of human brain temperature and the corresponding changes in oxygen metabolism during functional activation in a series of healthy subjects; to determine the range of these changes and their dependence on stimulus strength and duration. To determine the consequences of the disproportionate increase in blood flow compared to oxygen consumption, which occurs during functional activation, on brain temperature regulation. The potential implications of these results are significant. A powerful tool presents itself for analysis of the coupling of metabolic and physiologic control and for elucidation of details of the fundamental Blood Oxygenation Level Dependent contrast in MR.
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