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NOVEL METHODOLOGY FOR STUDYING OXIDATIVE METABOLISM

$8,672P41FY2010RRNIH

University Of Pennsylvania, Philadelphia PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The metabolic demands of the brain are met almost exclusively through metabolism of glucose. Under normal conditions, the brain consistently extracts about 50% of the oxygen in the blood. The changes in metabolic demand are matched by changes in blood flow rather than by changes in oxygen extraction. Regional variations in oxidative metabolism typically correlate well with regional variations in blood flow. The correlation is the rationale for substituting blood flow maps for oxygen consumption maps. There are no clinically used methods for the detection of oxidative metabolism in-vivo though metabolic disturbances in many diseases are important. In the past, in order to have a suitable model, 17O MRI techniques are modeled in swine to measure hemispheric cerebral metabolic rate of oxygen consumption (CMRO2) by detection of metabolically produced H217O by rapid T1[unreadable]-wieghted proton magnetic resonance imaging on a 1.5 T clinical scanner. The 17O is delivered as oxygen gas by a custom, minimal-loss, precision delivery breathing circuit and converted to H[unreadable]217O by oxidative metabolism. A high temporal resolution pulse sequence is employed to measure CMRO2. Proton measurements of signal change due to metabolically produced water are correlated with 17O in-vivo measurements. Using these techniques, the hemispheric CMRO2 in swine is estimated to be 1.23 [unreadable]0.26 [unreadable]mol/g/min;consistent with existing literature values. In the present study, we employed diffuse reflectance and correlation spectroscopy to monitor the response of cerebral oxygenation and blood flow to hypercapnia in swine and to compare oxygen consumption optically estimated with17O MRI measurements.

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