With age, the brain undergoes comprehensive changes in its function and physiology. Cerebral metabolism and blood supply are among the key physiologic processes supporting the daily function of the brain and may play an important role in age-related cognitive decline. Using MRI, it is now possible to make quantitative assessment of these parameters in a noninvasive manner. In the present study, we concurrently measured cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and venous blood oxygenation in a well-characterized healthy adult cohort from 20 to 89 years old (N = 232). Our data showed that CMRO(2) increased significantly with age, while CBF decreased with age. This combination of higher demand and diminished supply resulted in a reduction of venous blood oxygenation with age. Regional CBF was also determined, and it was found that the spatial pattern of CBF decline was heterogeneous across the brain with prefrontal cortex, insular cortex, and caudate being the most affected regions. Aside from the resting state parameters, the blood vessels' ability to dilate, measured by cerebrovascular reactivity to 5% CO(2) inhalation, was assessed and was reduced with age, the extent of which was more prominent than that of the resting state CBF.

Recently, a T2-Relaxation-Under-Spin-Tagging (TRUST) MRI technique was developed to quantitatively estimate blood oxygen saturation fraction (Y) via the measurement of pure blood T2. This technique has shown promise for normalization of fMRI signals, for the assessment of oxygen metabolism, and in studies of cognitive aging and multiple sclerosis. However, a human validation study has not been conducted. In addition, the calibration curve used to convert blood T2 to Y has not accounted for the effects of hematocrit (Hct). In the present study, we first conducted experiments on blood samples under physiologic conditions, and the Carr-Purcell-Meiboom-Gill (CPMG) T2 was determined for a range of Y and Hct values. The data were fitted to a two-compartment exchange model to allow the characterization of a three-dimensional plot that can serve to calibrate the in vivo data. Next, in a validation study in humans, we showed that arterial Y estimated using TRUST MRI was 0.837±0.036 (N=7) during the inhalation of 14% O2, which was in excellent agreement with the gold-standard Y values of 0.840±0.036 based on Pulse-Oximetry. These data suggest that the availability of this calibration plot should enhance the applicability of TRUST MRI for non-invasive assessment of cerebral blood oxygenation.

A better understanding of carbon dioxide (CO 2 ) effect on brain activity may have a profound impact on clinical studies using CO 2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO 2 , via inhalation of 5% CO 2 , may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO 2 ) by 13.4% ± 2.3% (N = 14) and, furthermore, the CMRO 2 change was proportional to the subject's end-tidal CO 2 (Et-CO 2 ) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visualevoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO 2 inhalation.

Pseudocontinuous arterial spin labeling MRI is a new arterial spin labeling technique that has the potential of combining advantages of continuous arterial spin labeling and pulsed arterial spin labeling. However, unlike continuous arterial spin labeling, the labeling process of pseudocontinuous arterial spin labeling is not strictly an adiabatic inversion and the efficiency of labeling may be subject specific. Here, three experiments were performed to study the labeling efficiency in pseudocontinuous arterial spin labeling MRI. First, the optimal labeling position was determined empirically to be approximately 84 mm below the anterior commissure-posterior commissure line in order to achieve the highest sensitivity. Second, an experimental method was developed to utilize phase-contrast velocity MRI as a normalization factor and to estimate the labeling efficiency in vivo, which was founded to be 0.86 6 0.06 (n 5 10, mean 6 standard deviation). Third, we compared the labeling efficiency of pseudocontinuous arterial spin labeling MRI under normocapnic and hypercapnic (inhalation of 5% CO 2 ) conditions and showed that a higher flow velocity in the feeding arteries resulted in a reduction in the labeling efficiency. In summary, our results suggest that labeling efficiency is a critical parameter in pseudocontinuous arterial spin labeling MRI not only in terms of achieving highest sensitivity but also in quantification of absolute cerebral blood flow in milliliters per minute per 100 g. We propose that the labeling efficiency should be estimated using phase-contrast velocity MRI on a subject-specific basis. Magn Reson Med 63:765-771,

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...