Understanding brain energy metabolism and cerebral blood flow using advanced MRI approaches

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The cerebral metabolic rate of oxygen (CMRO2) is the rate of oxygen consumption by the brain and is one of the most important physiological indicators of brain vitality and function. The quantification of regional CMRO2 provides a critical tool for understanding cerebral energy demands and the metabolic components of neural signalling. Our overarching hypothesis is that regional measures of cerebral metabolism, coupled with simultaneous regional measures of cerebral blood flow (CBF) will provide the basis for a better quantitative understanding of cerebral physiology and functional neuroimaging studies. ***The current gold standard for quantification of regional CMRO2 is positron emission tomography. However, this modality exposes subjects to high doses of radiation and thus is not suitable for repeated studies. Recent MRI research on non-invasive CMRO2 quantification has mostly focused on proton (1H) imaging, making it the most promising technique to date. However, there are many technical challenges, such as long acquisition time, poor spatial resolution and non-specific signal localization, which must be addressed before regional CMRO2 can be used to gain an understanding of basic human cerebral physiology. This proposal will address these technical challenges and enable rapid and robust whole-brain maps of regional metabolism using 1H MRI. A promising alternative approach is hyperpolarized 129xenon (HP 129Xe) MRI, which offers rapid measurement of blood flow and arterial and venous oxygenation, blood pool specific signal, and no background interference, but has not yet been utilized for CMRO2 mapping. Although HP 129Xe MRI presents more technical challenges, it may enable us to relax some of the physiological assumptions made with 1H MRI.***The long-term goal of this program is to enhance our understanding of regional brain physiology and metabolism using MRI. The short term objectives are to develop a novel robust 1H MRI protocol for high resolution regional quantification of CMRO2 in rodents based on measures of CBF and venous oxygen saturation. We will also develop the first in vivo measurement of regional CMRO2 in the rodent brain by exploiting our encouraging pilot data using HP 129Xe MRI and compare it against our 1H MRI measurements.***In summary, my program will develop novel, non-invasive, in vivo, regional CMRO2 measures using advanced MRI methods which will provide a framework for investigating brain energy metabolism and blood flow. This will enable a wide range of applications such as investigating regional oxygenation in the developing brain, and during exercise and sleep. Moreover, absolute regional measures of CMRO2 will advance the interpretation of functional neuroimaging signals, which are comprised of multiple competing physiological processes. MRI measures of neural activity cannot be uniquely interpreted until individual signal components are better understood. ********