Noninvasive quantification of whole‐brain cerebral metabolic rate of oxygen (CMRO₂) by MRI

Abstract

Cerebral metabolic rate of oxygen (CMRO 2 ) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO 2 with positron emission tomography (PET) or MRI involve special equipment and/or exogenous agents, and may not be suitable for routine clinical studies. In the present study, a noninvasive method is developed to estimate whole-brain CMRO 2 in humans. This method applies phase-contrast MRI for quantitative blood flow measurement and T 2 -relaxation-under-spin-tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO 2 . Whole-brain averaged CMRO 2 values in young, healthy subjects were 132.1 ؎ 20.0 mol/100 g/min, in good agreement with literature reports using PET. Various acquisition strategies for phasecontrast and TRUST MRI were compared, and it was found that nongated phase-contrast and sagittal sinus (SS) TRUST MRI were able to provide the most efficient and accurate estimation of CMRO 2 . In addition, blood flow and venous oxygenation were found to be positively correlated across subjects. Owing to the noninvasive nature of this method, it may be a con The brain represents about 2% of the total body weight, but consumes about 20% of the total energy (1,2). The energy demand of the brain is met primarily by aerobic metabolism (3). Therefore, the cerebral metabolic rate of oxygen (CMRO 2 ) is an important index of tissue viability and brain function. Many conditions are related to alterations in oxygen metabolism, such as Huntington's disease (4), Alzheimer's disease (5) and normal aging (6). In addition, quantitative measurement of CMRO 2 is useful in understanding normal cerebral physiology during resting state, sleep, brain activation, and physiologic challenges.The measurement of CMRO 2 is not yet a routine procedure. Currently available techniques for CMRO 2 measurement require the infusion/injection/inhalation of an exogenous agent. Positron emission tomography (PET) is a widely used technique using radioactively-labeled 15 O (7). NMR methods use either 13 C-glucose (8,9) or 17 O-oxygen to estimate CMRO 2 (10,11), and are most often used in animal studies. Several reasons may have contributed to the difficulties in applying these techniques in routine clinical studies: 1) the procedure is quite invasive due to the use of exogenous agent with potential exposure to radiation (in PET) and the need of arterial/venous lines; 2) the relatively long duration of the procedure, which includes preparation, multiple injections, agent clearance, etc.; 3) the relatively high cost due to the need for special equipment (e.g., cyclotron) or a special agent (e.g., 17 O). For studies of brain activation, an approach to estimate relative changes in CMRO 2 , termed calibrated functional MRI (fMRI), has been developed (12-18), which measures neural activity-induced blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) changes and compares them to those induced by physiologic cha...

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