Measuring brain oxygenation in humans using a multiparametric quantitative blood oxygenation level dependent MRI approach

Quantitative blood oxygenation level dependent approaches have been designed to obtain quantitative oxygenation information using MRI. A mathematical model is usually fitted to the time signal decay of a gradient‐echo and spin‐echo measurements to derive hemodynamic parameters such as the blood oxygen saturation or the cerebral blood volume. Although the results in rats and human brain have been encouraging, recent studies have pointed out the need for independent estimation of one or more variables to increase the accuracy of the method. In this study, a multiparametric quantitative blood oxygenation level dependent approach is proposed. A combination of arterial spin labeling and dynamic susceptibility contrast methods were used to obtain quantitative estimates of cerebral blood volume and cerebral blood flow. These results were combined with T and T₂ measurements to derive maps of blood oxygen saturation or cerebral metabolic rate of oxygen. In 12 normal subjects, a mean cerebral blood volume of 4.33 ± 0.7%, cerebral blood flow of 43.8 ± 5.7 mL/min/100 g, blood oxygen saturation of 60 ± 6% and cerebral metabolic rate of oxygen 157 ± 23 μmol/100 g/min were found, which are in agreement with literature values. The results obtained in this study suggest that this methodology could be applied to study brain hypoxia in the setting of pathology. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Dynamics of blood flow and oxygenation changes during brain activation: The balloon model

A biomechanical model is presented for the dynamic changes in deoxyhemoglobin content during brain activation. The model incorporates the conflicting effects of dynamic changes in both blood oxygenation and blood volume. Calculations based on the model show pronounced transients in the deoxyhemoglobin content and the blood oxygenation level dependent (BOLD) signal measured with functional MRI, including initial dips and overshoots and a prolonged post-stimulus undershoot of the BOLD signal. Furthermore, these transient effects can occur in the presence of tight coupling of cerebral blood flow and oxygen metabolism throughout the activation period. An initial test of the model against experimental measurements of flow and BOLD changes during a finger-tapping task showed good agreement.     

Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man

Changes in glucose consumption, lactate production, and blood oxygenation were measured during prolonged neuronal activation (4–6 min) in human primary visual cortex using dynamic magnetic resonance spectroscopy and imaging. A decrease of steady-state glucose by 40% because of enhanced use by 21% was accompanied by a transient accumulation of lactate with a peak value of 170% 2.5 min after stimulation onset Rapid blood hyperoxygenation indicating ?uncoupling”? of blood flow and oxidative metabolism was followed by a return to basal levels over 3 min. Thus, initial nonoxidative glucose consumption during functional activation is gradually complemented by a slower adjustment of oxidative phosphorylation that ?recouples”? perfusion and oxygen consumption at a new equilibrium.     

Baseline blood oxygenation modulates response amplitude: Physiologic basis for intersubject variations in functional MRI signals

Although BOLD functional MRI (fMRI) provides a useful tool for probing neuronal activities, large intersubject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task‐evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T₂ relaxation under spin‐tagging (TRUST) MRI, which yielded baseline oxygenation of 63.7% ± 7.2% in the sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal, and vice versa. For every 10% difference in baseline oxygenation across subjects, BOLD and cerebral blood flow (CBF) signals differ by –0.4% and –30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject. Magn Reson Med 60:364–372, 2008. © 2008 Wiley‐Liss, Inc.     

Evaluation of MRI models in the measurement of CMRO2 and its relationship with CBF

The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO₂) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single‐compartment model (SCM) and the multicompartment model (MCM), were used to determine the relative changes in CMRO₂ using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; α = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and α from measured δCBV and δCBF); and [3] MCM. The magnitude of relative changes in CMRO₂ and the nonlinear relationship between CBF and CMRO₂ obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO₂ and determining the flow‐metabolism relationship. Magn Reson Med 60:380–389, 2008. © 2008 Wiley‐Liss, Inc.     

CBF, BOLD, CBV, and CMRO(2) fMRI signal temporal dynamics at 500-msec resolution

PURPOSE: To investigate the temporal dynamics of blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2)) changes due to forepaw stimulation with 500-msec resolution in a single setting. MATERIALS AND METHODS: Forepaw stimulation and hypercapnic challenge on rats were studied. CBF and BOLD functional MRI (fMRI) were measured using the pseudo-continuous arterial spin-labeling technique at 500-msec resolution. CBV fMRI was measured using monocrystalline iron-oxide particles following CBF and BOLD measurements in the same animals. CMRO(2) change was estimated via the biophysical BOLD model with hypercapnic calibration. Percent changes and onset times were analyzed for the entire forepaw somatosensory cortices and three operationally defined cortical segments, denoted Layers I-III, IV-V, and VI. RESULTS: BOLD change was largest in Layers I-III, whereas CBF, CBV, and CMRO(2) changes were largest in Layers IV-V. Among all fMRI signals in all layers, only the BOLD signal in Layers I-III showed a poststimulus undershoot. CBF and CBV dynamics were similar. Closer inspection showed that CBV increased slightly first (P < 0.05), but was slow to peak. CBF increased second, but peaked first. BOLD significantly lagged both CBF and CBV (P < 0.05). CONCLUSION: This study provides important temporal dynamics of multiple fMRI signals at high temporal resolution in a single setting.     

Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation

The modulation of blood oxygenation level-dependent (BOLD) cerebral MRI contrast by the vasoconstrictive drug indomethacin (i.v. 0.2 mg/kg b.w.) was investigated in 10 healthy young adults without and with functional challenge (repetitive and sustained visual activation). For comparison, isotonic saline (placebo, 20 mL) and acetylsalicylate (i.v. 500 mg) were investigated as well, each in separate sessions using identical protocols. After indomethacin, dynamic T2*-weighted echo-planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%-2.6% in different gray matter regions (P < or = 0.001 compared to placebo), which was not observed for acetylsalicylate and the placebo condition. Regional signal differences were not significant within gray matter, but all gray matter regions differed significantly from the signal decrease of only 1.2% +/- 0.7% observed in white matter (P = 0.001). For the experimental parameters used, a 1% MRI signal decrease in response to indomethacin was estimated to correlate with a decrease of the cerebral blood flow by about 12 ml/100 g/minute, and an increase of the oxygen extraction fraction by about 15%. Responses to visual activation were not affected by saline or acetylsalicylate, and yielded 5.0%-5.5% BOLD MRI signal increases both before and after drug application. In contrast, indomethacin reduced the initial response strength to 82%-85% of that obtained without the drug. The steady-state response during sustained activation reached only 47% of the corresponding pre-drug level (P < 0.01). During repetitive activation the BOLD contrast was reduced to 66% of that observed for control conditions (P < 0.001). In conclusion, indomethacin attenuates the vasodilatory force at functional brain activation, indicating different mechanisms governing neurovascular coupling.     

Contribution of Sinerem® used as blood-pool contrast agent: Detection of cerebral blood volume changes during apnea in the rabbit

The authors suggest that ultra-small paramagnetic iron oxide (USPIO) particles used as blood pool contrast agents may increase the sensitivity of midfield MRI (i.e., less than 1.5 Tesla) to physiological variations in cerebral blood volume. This hypothesis was tested on a rabbit model of apnea which increases pCO₂ and cerebral blood volume. Using Sinerem® as the USPIO at a blood concentration of 60 μmol iron/kg body weight, an 8% T₂*-weighted signal decrease could be observed at 1.0 T with 25–33% increase in pCO₂. Comparatively, in the absence of USPIO, T₂*-weighted signal dropped only 4% during apnea and after mild hyperoxygenation beforehand, due to increased deoxyhemoglobin content. These preliminary data suggest that USPIOs could play an important role in functional MRI at midfield strength, by sensitizing the signal to cerebral blood volume changes.     

Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.     

Estimating cerebral blood volume with expanded vascular space occupancy slice coverage

A model for quantifying cerebral blood volume (CBV) based on the vascular space occupancy (VASO) technique and varying the extent of blood nulling yielding task‐related signal changes with various amounts of blood oxygenation level‐dependent (BOLD) and VASO weightings was previously described. Challenges associated with VASO include limited slice coverage and the confounding inflow of fresh blood. In this work, an approach that extends the previous model to multiple slices and accounts for the inflow effect is described and applied to data from a multiecho sequence simultaneously acquiring VASO, cerebral blood flow (CBF), and BOLD images. This method led to CBV values (7.9 ± 0.3 and 5.6 ± 0.3 ml blood/100 ml brain during activation [CBV_ACT] and rest [CBV_REST], respectively) consistent with previous studies using similar visual stimuli. Furthermore, an increase in effective blood relaxation (0.65 ± 0.01) compared to the published value (0.62) was detected, likely reflecting inflow of fresh blood. Finally, cerebral metabolic rate of oxygen (CMRO₂) estimates using a multiple compartment model without assumption of CBV_REST led to estimates (18.7 ± 17.0%) that were within published ranges. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

An evaluation of the sensitivity of the intravoxel incoherent motion (IVIM) method of blood flow measurement to changes in cerebral blood flow

To evaluate the sensitivity of the intravoxel incoherent motion (IVIM) technique to changes in cerebral blood flow, we made measurements of IVIM parameters in rat brain under conditions of altered arterial pCO₂. The arterial pCO₂, was varied over a range which would be expected to change cerebral blood flow from roughly 50 to 500 ml/(100 g·min). The IVIM measurements were made with suppression of extravascular water signal. The parameters f′ (the apparent fraction of spins which have “fast” pseudodiffusion), D (the “fast-pseudodiffusion” coefficient), and D(the “slow-pseudodiffusion” coefficient) all showed statistically significant positive linear correlations with arterial pCO₂. These results suggest that the IVIM method, when used with suppression of extravascular water signal, is sensitive to changes in blood flow.     

Feasibility study of exploring a T₁-weighted dynamic contrast-enhanced MR approach for brain perfusion imaging

Purpose:

To investigate the feasibility of T₁‐weighted dynamic contrast‐enhanced (DCE) MRI for the measurement of brain perfusion.

Materials and Methods:

Dynamic imaging was performed on a 3.0 Tesla (T) MR scanner by using a rapid spoiled‐GRE protocol. T₁ measurement with driven equilibrium single pulse observation of T₁ (DESPOT1) was used to convert the MR signal to tracer concentration. Cerebral perfusion maps were obtained by using an improved gamma‐variate model in 10 subjects and compared with those with arterial spin label (ASL) approach.

Results:

The cerebral blood volume (CBV) values were calculated as 4.74 ± 1.09 and 2.29 ± 0.58 mL/100 g in gray matter (GM) and whiter matter (WM), respectively. Mean transit time (MTT) values were 6.15 ± 0.59 s in GM and 6.96 ± 0.79 s in WM. The DCE values for GM/WM cerebral blood flow (CBF) were measured as 53.41 ± 9.23 / 25.78 ± 8.91 mL/100 g/min, versus ASL values of 49.05 ± 10.81 / 23.00 ± 5.89 mL/100 g/min for GW/WM. Bland‐Altman plot revealed a small difference of CBF between two approaches (mean bias = 3.83 mL/100 g/min, SD = 11.29). There were 6 pairs of samples (5%, 6/120) beyond the 95% limits of agreement. The correlation plots showed that the slop of Y (CBF__DCE) versus X intercept (CBF__ASL) is 0.95 with the intercept of 4.53 mL/100 g/min (r = 0.74; P < 0.05).

Conclusion:

It is feasible to evaluate the cerebral perfusion by using T₁‐weighted DCE‐MRI with the improved kinetic model. J. Magn. Reson. Imaging 2012;35:1322–1331. © 2012 Wiley Periodicals, Inc.     

Effects of CBV,CBF, and blood‐brain barrier permeability on accuracy of PASL and VASO measurement

Cerebral blood flow, cerebral blood volume (CBV), and water permeability through blood‐brain barrier are important hemodynamic parameters in brain physiology. Pulsed arterial spin labeling and vascular‐space occupancy techniques have been used to measure regional cerebral blood flow and CBV, respectively. However, these techniques generally ignore the effects of one hemodynamic parameter on the measurement of others. For instance, the influences of CBV changes on arterial spin labeling or the permeability effects on vascular‐space occupancy typically were not accounted for in the quantification of blood flow or volume. In the current work, the biophysical effects of CBV on pulsed arterial spin labeling and permeability on vascular‐space occupancy signals are evaluated using a general two‐compartment model. The dependence of these effects on the T₁ at various field strengths is also assessed by simulations. Results indicate that CBV has negligible to small influences on pulsed arterial spin labeling signal (<6.6% at 3 T) and permeability effects are negligible on vascular‐space occupancy signal (<0.1% at 3 T) under normal physiologic conditions. In addition, CBV effect on pulsed arterial spin labeling is further diminished at high field strengths, but residual blood contamination in vascular‐space occupancy signal may be enhanced at high fields due to the reduced difference between extra‐ and intravascular T₁ values. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation.

Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses.     

Calibration and validation of TRUST MRI for the estimation of cerebral blood oxygenation

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 this study, we first conducted experiments on blood samples under physiologic conditions, and the Carr‐Purcell‐Meiboom‐Gill 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 T₂‐Relaxation‐Under‐Spin‐Tagging MRI for noninvasive assessment of cerebral blood oxygenation. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

On the measurement of absolute cerebral blood volume (CBV) using vascular‐space‐occupancy (VASO) MRI

Recently, a vascular‐space‐occupancy (VASO) MRI technique was developed for quantitative assessment of cerebral blood volume (CBV). This method uses the T₁‐shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) with imaging parameters chosen that null the precontrast blood magnetization but allow the postcontrast blood magnetization to recover to equilibrium. A key advantage of VASO CBV estimation is that it provides a straightforward procedure for converting MR signals to absolute physiologic values. However, as with other T₁‐based steady‐state approaches, several important factors need to be considered that influence the accuracy of CBV values obtained with VASO MRI. Here, the transverse relaxation (T₂/T) effect in VASO MRI was investigated using multiecho spin‐echo and gradient‐echo experiments, resulting in underestimation of CBV by 14.9% ± 1.1% and 16.0% ± 2.5% for spin echo (TE = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence of contrast agent clearance was studied by acquiring multiple postcontrast VASO images at 2.2‐min intervals, which showed that the concentration of Gd‐DTPA in the first 14 min (single dose) was sufficient for the blood magnetization to fully recover to equilibrium. Finally, the effect of vascular Gd‐DTPA leakage was assessed for scalp tissue, and signal extrapolation as a function of postinjection time was demonstrated to be useful in minimizing the associated errors. Specific recommendations for VASO MRI acquisition and processing strategies are provided. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

Test–retest reproducibility of a rapid method to measure brain oxygen metabolism

Cerebral metabolic rate of oxygen (CMRO₂) is an important index of tissue viability and brain function, but this parameter cannot yet be measured routinely on clinical scanners. Recently, a noninvasive technique was proposed which estimates global CMRO₂ by concomitantly measuring oxygen‐extraction‐fraction using T₂‐relaxation‐under‐spin‐tagging MRI and pulse oximetry, and cerebral‐blood‐flow using phase‐contrast MRI. This study sought to establish a standard acquisition procedure for this technique and to evaluate its test–retest reproducibility in healthy subjects. Each subject was examined in five sessions and each session included two measurements. Intrasession, intersession, and intersubject coefficients of variation for CMRO₂ were found to be 3.84 ± 1.44% (N = 7, mean ± standard deviation), 6.59 ± 1.56%, and 8.80% respectively. These reproducibility values were comparable or slightly superior to ¹⁵O positron emission tomography (PET) results reported in the literature. It was also found that oxygen‐extraction‐fraction and cerebral‐blood‐flow tended to co‐vary across sessions (P = 0.002) and subjects (P = 0.01), and their coefficients of variation were greater than that of CMRO₂. The simplicity and reliability features may afford this global CMRO₂ technique great potential for immediate clinical applications. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans

Purpose:

To examine the effect of acetazolamide, known to increase cerebral blood flow (CBF) and glyceryl trinitrate (GTN), known to increase cerebral blood volume (CBV) on the blood oxygenation level‐dependent (BOLD) response in humans using 3 T magnetic resonance imaging (MRI), and to evaluate how pharmacological agents may modulate cerebral hemodynamic and thereby possibly the BOLD signal.

Materials and Methods:

Six subjects were randomly allocated to receive acetazolamide, GTN, or placebo in a double‐blind three‐way crossover controlled study. Before, during, and after drug administration we recorded the BOLD response during visual stimulation with reversing checkerboard.

Results:

We found that acetazolamide caused significant depression of the BOLD response (P = 0.0066). The maximum decrease occurred at 5 minutes after infusion and was 51.9% (95% confidence interval [CI], 22.03–81.76). GTN did not influence the BOLD response (P = 0.55).

Conclusion:

The BOLD response is decreased during increased CBF by acetazolamide, suggesting an inverse relationship between global CBF and the BOLD response. GTN does not change the BOLD response. This indicates that GTN exerts an effect on the large vessels only and that CBV changes in the microvascular system are necessary to alter the BOLD response. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

In vivo measurement of CBF using 17O NMR signal of metabolically produced H217O as a perfusion tracer

The cerebral metabolic rate of oxygen of small animals can be reliably imaged using the in vivo ¹⁷O magnetic resonance approach at high field. However, a separate measurement is required for imaging the cerebral blood flow in the same animal. In this study, we demonstrate that the ¹⁷O NMR signal of metabolically produced H₂¹⁷O in the rat brain following an ¹⁷O₂ inhalation can serve as a perfusion tracer and its decay rate can be used to determine the absolute values of cerebral blood flow across a wide range of animal conditions. This finding suggests that the in vivo ¹⁷O magnetic resonance approach is capable of imaging both cerebral metabolic rate of oxygen and cerebral blood flow simultaneously and noninvasively; and it provides new utilities for studying the cerebral oxygen metabolism and perfusion commonly associated with brain function and diseases. Magn Reson Med 70:309–314, 2013. © 2012 Wiley Periodicals, Inc.     

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

Cerebral metabolic rate of oxygen (CMRO₂) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO₂ 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 CMRO₂ in humans. This method applies phase‐contrast MRI for quantitative blood flow measurement and T₂‐relaxation‐under‐spin‐tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO₂. Whole‐brain averaged CMRO₂ values in young, healthy subjects were 132.1 ± 20.0 μmol/100 g/min, in good agreement with literature reports using PET. Various acquisition strategies for phase‐contrast 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 CMRO₂. 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 convenient and useful approach for assessment of brain metabolism in brain disorders as well as under various physiologic conditions. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.