Comparison of diffusion-weighted high-resolution CBF and spin-echo BOLD fMRI at 9.4 T.

The quantification of blood oxygenation-level dependent (BOLD) functional MRI (fMRI) signals is closely related to cerebral blood flow (CBF) change; therefore, understanding the exact relationship between BOLD and CBF changes on a pixel-by-pixel basis is fundamental. In this study, quantitative CBF changes induced by neural activity were used to quantify BOLD signal changes during somatosensory stimulation in alpha-chloralose-anesthetized rats. To examine the influence of fast-moving vascular spins in quantifying CBF, bipolar gradients were employed. Our data show no significant difference in relative CBF changes obtained with and without bipolar gradients. To compare BOLD and CBF signal changes induced by neural stimulation, a spin-echo (SE) sequence with long SE time of 40 ms at 9.4 T was used in conjunction with an arterial spin labeling technique. SE BOLD changes were quantitatively correlated to CBF changes on a pixel-by-pixel and animal-by-animal basis. Thus, SE BOLD-based fMRI at high magnetic fields allows a quantitative comparison of functional brain activities across brain regions and subjects.     

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.     

Physiological origin of low‐frequency drift in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI)

We investigated the biophysical mechanism of low‐frequency drift in blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) (0.00–0.01 Hz), by exploring its spatial distribution, dependence on imaging parameters, and relationship with task‐induced brain activation. Cardiac and respiratory signals were concurrently recorded during MRI scanning and subsequently removed from MRI data. It was found that the spatial distribution of low‐frequency drifts in human brain followed a tissue‐specific pattern, with greater drift magnitude in the gray matter than in white matter. In gray matter, the dependence of drift magnitudes on TE was similar to that of task‐induced BOLD signal changes, i.e., the absolute drift magnitude reached the maximum when TE approached T whereas relative drift magnitude increased linearly with TE. By systematically varying the flip angle, it was found that drift magnitudes possessed a positive dependence on image intensity. In phantom experiments, the observed drift was not only much smaller than that of human brain, but also showed different dependence on TE and flip angle. In fMRI studies with visual stimulation, a strong positive correlation between drift effects at baseline and task‐induced BOLD signal changes was observed both across subjects and across activated pixels within individual participants. We further demonstrated that intrinsic, physiological drift effects are a major component of the spontaneous fluctuations of BOLD fMRI signal within the frequency range of 0.0–0.1 Hz. Our study supports brain physiology, as opposed to scanner instabilities or cardiac/respiratory pulsations, as the main source of low‐frequency drifts in BOLD fMRI. Magn Reson Med 61, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Simultaneous oxygenation and perfbsion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: Quantitative correlation between BOLD and CBF changes

A relationship between regional cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) changes in the primary visual cortex (V1) at varied visual stimulation fre quency has been examined quantitatively using the multislice FAIR technique. A linear correlation in the common activation areas between functional BOLD and CBF maps was observed. This supports the hypothesis that the task-stimulated BOLD changes in microvasculature are correlated with the CBF changes that presumably reflect the degree of neuronal ac tivity. The linear correlation coefficients for intrasubject com parisons are more significant than those for intersubject com parisons. This suggests that using intrasubject comparisons for quantitative studies of neuronal activity related to different task stimuli and task performances should be more reliable than using intersubject comparisons.     

Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI.

The transient relationship between arterial cerebral blood flow (CBF(A)) and total cerebral blood volume (CBV(T)) was determined in the rat brain. Five rats anesthetized with urethane (1.2 g/kg) were examined under graded hypercapnia conditions (7.5% and 10% CO(2) ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBV(T) changes were determined after injection of a monocrystalline iron oxide nanocolloid (MION) contrast agent using an iron dose of 12 mg/kg. The relationship between CBV(T) and CBF(A) under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBV(T) and CBF(A) is region-specific. Voxels with > or =15% BOLD signal changes from hypercapnia (7.5% CO(2) ventilation) have a larger power index (alpha = 3.26), a larger maximum possible BOLD response (M = 0.85), and shorter T(*)(2) (32 ms) caused by deoxyhemoglobin, compared to voxels with <15% BOLD signal changes (alpha = 1.82, M = 0.16, and T(*)(2) = 169 ms). It is suggested that the biophysical model of the BOLD signal can be extended under the transient state, with a caution that alpha and M values are region-specific. To avoid overestimation of the cerebral metabolic rate of oxygen changes seen using fMRI, caution should be taken to not include voxels with large veins and a large BOLD signal.     

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation.

The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can be estimated during neural activity using a reference condition obtained with known CMRO2 change. In this work, nine subjects were studied at a magnetic field of 1.5 T; each subject underwent inhalation of a 5% carbon dioxide gas mixture as a reference and two visual stimulation studies. Relative CBF and BOLD signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec(-1), which corresponds to BOLD signal change of 2.4 +/- 0.7% with a gradient echo time of 50 msec. During black/white visual stimulation reversing at 8 Hz, regional CBF increase in the visual cortex was 43.6 +/- 9.4% (n = 18), and deltaR2* was -0.114 +/- 0.086 sec(-1), corresponding to a BOLD signal change of 0.6 +/- 0.4%. Assuming that CMRO2 does not change during hypercapnia and that hemodynamic responses during hypercapnia and neural stimulation are similar, relative CMRO2 change was determined using BOLD biophysical models. The average CMRO2 change in the visual cortex ranged from 15.6 +/- 8.1% (n = 18) with significant cerebral blood volume (CBV) contribution to 29.6 +/- 18.8% without significant CBV contribution. A weak positive correlation between CBF and CMRO2 changes was observed, suggesting the CMRO2 increase is proportional to the CBF increase.     

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.     

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.     

Functional MRI of calcium-dependent synaptic activity: cross correlation with CBF and BOLD measurements.

Spatial specificities of the calcium-dependent synaptic activity, hemodynamic-based blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI were quantitatively compared in the same animals. Calcium-dependent synaptic activity was imaged by exploiting the manganese ion (Mn++) as a calcium analog and an MRI contrast agent at 9.4 T. Following forepaw stimulation in alpha-chloralose anesthetized rat, water T1 of the contralateral forepaw somatosensory cortex (SI) was focally and markedly reduced from 1.99 +/- 0.03 sec to 1.30 +/- 0.18 sec (mean +/- SD, N = 7), resulting from the preferential intracellular Mn++ accumulation. Based on an in vitro calibration, the estimated contralateral somatosensory cortex [Mn++] was approximately 100M, which was 2-5-fold higher than the neighboring tissue and the ipsilateral SI. Regions with the highest calcium activities were localized around cortical layer IV. Stimulus-induced BOLD and CBF changes were 3.4 +/- 1.6% and 98 +/- 33%, respectively. The T1 synaptic activity maps extended along the cortex, whereas the hemodynamic-based activation maps extended radially along the vessels. Spatial overlaps among the synaptic activity, BOLD, and CBF activation maps showed excellent co-registrations. The center-of-mass offsets between any two activation maps were less than 200 microm, suggesting that hemodynamic-based fMRI techniques (at least at high field) can be used to accurately map the spatial loci of synaptic activity.     

Detrimental effects of BOLD signal in arterial spin labeling fMRI at high field strength.

Arterial spin labeling (ASL) MRI is a useful technique for noninvasive measurement of cerebral blood flow (CBF) in humans. High field strength provides a unique advantage for ASL because of longer blood T(1) relaxation times, making this technique a promising quantitative approach for functional brain mapping. However, higher magnetic field also introduces new challenges. Here it is shown that the CBF response determined using ASL functional MRI (fMRI) at 3.0 T contains significant contamination from blood-oxygenation-level-dependent (BOLD) effects. Due to interleaved acquisitions of label and control images, difference in blood oxygenation status between these two scans can cause incomplete cancellation of the static signal upon image subtraction, resulting in a BOLD-related artifact in the estimated CBF hemodynamics. If not accounted for, such an effect can complicate the interpretation of the ASL results, e.g., causing a delayed onset and offset of the response, or inducing an artifactual poststimulus undershoot. The BOLD contribution also decreases the sensitivity of ASL-based fMRI. Correction methods are proposed to reduce the artifact, giving increased number of activated voxels (18+/-5%, P=0.006) and more accurate estimation of CBF temporal characteristics.     

Comparison of blood oxygenattion and cerebral blood flow effect in fMRI: Estimation of relative oxygen consumption change

The most widely-used functional magnetic resonance imaging (fMRI) technique is based on the blood oxygenation level dependent (BOLD) effect, which requires at least partial uncoupling between cerebral blood flow (CBF) and oxygen consumption changes during increased mental activity. To compare BOLD and CBF effects during tasking, BOLD and flowsensitive alternating inversion recovery (FAIR) images were acquired during visual stimulation with red goggles at a frequency of 8 Hz in an inteerleaved fashion. With the FAIR technique, absolute and relative CBF changes were determined. Relative oxygen consumption changes cdan be estimated using the BOLD and relative CBF changes. In gray matter areas in the visual cortex, absolute and relative CBF changes in humans during photic stimulation were 31 ± 11 SD ml/100 g tissue/min and 43 ± 16 SD % (n =12), respectively, while the relative oxygen consumption change was close to zero. These findings agree extremely well with previouse results using positron emission tomography. The BOLD signal change is not linearly correlated with the relative CBF increase across subjects and negatively correlates with the oxygen consumption change. Caution should be exercised when interpreting the BOLD percent change as a quantitative index of the CBF change, especially in inter-subject comparisons.     

Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model.

The relationship between blood oxygenation level-dependent (BOLD) MRI signals, cerebral blood flow (CBF), and oxygen consumption (CMR(O2)) in the physiological steady state was investigated. A quantitative model, based on flow-dependent dilution of metabolically generated deoxyhemoglobin, was validated by measuring BOLD signals and relative CBF simultaneously in the primary visual cortex (V1) of human subjects (N = 12) during graded hypercapnia at different levels of visual stimulation. BOLD and CBF responses to specific conditions were averaged across subjects and plotted as points in the BOLD-CBF plane, tracing out lines of constant CMR(O2). The quantitative deoxyhemoglobin dilution model could be fit to these measured iso-CMR(O2) contours without significant (P 相似文献   

Comparison of BOLD and direct‐MR neuronal detection (DND) in the human visual cortex at 3T

Direct‐MR neuronal detection (DND) of transient magnetic fields has recently been investigated as a novel imaging alternative to the conventional BOLD functional MRI (fMRI) technique. However, there remain controversial issues and debate surrounding this methodology, and this study attempts clarification by comparing BOLD responses in the human visual system with those of DND. BOLD relies on indirectly measuring blood oxygenation and flow changes as a result of neuronal activity, whereas the putative DND method is based on the hypothesis that the components of the in vivo neuronal magnetic fields, which lie parallel to the B₀ field, can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. Block paradigms of checkerboard patterns were used for visual stimulation in both DND and BOLD experiments, allowing detection based on different frequency responses. This study shows colocalization of some voxels with slow BOLD responses and putative fast DND responses using General Linear Model (GLM) analysis. Frequency spectra for the activated voxel cluster are also shown for both stimulated and control data. The mean percentage signal change for the DND responses is 0.2%, corresponding to a predicted neuronal field of 0.14 nT. Magn Reson Med 60:1147–1154, 2008. © 2008 Wiley‐Liss, Inc.     

High-resolution, spin-echo BOLD, and CBF fMRI at 4 and 7 T.

With growing interest in noninvasive mapping of columnar organization and other small functional structures in the brain, achieving high spatial resolution and specificity in fMRI is of critical importance. We implemented a simple method for BOLD and perfusion fMRI with high spatial resolution and specificity. Increased spatial resolution was achieved by selectively exciting a slab of interest along the phase-encoding direction for EPI, resulting in a reduced FOV and number of phase-encoding steps. Improved spatial specificity was achieved by using SE EPI acquisition at high fields, where it is predominantly sensitive to signal changes in the microvasculature. Robust SE BOLD and perfusion fMRI were obtained with a nominal in-plane resolution up to 0.5 x 0.5 mm(2) at 7 and 4 Tesla, and were highly reproducible under repeated measures. This methodology enables high-resolution and high-specificity studies of functional topography in the millimeter to submillimeter spatial scales of the human brain.     

Characterization of effects of mean arterial blood pressure induced by cocaine and cocaine methiodide on BOLD signals in rat brain.

A total of 45 male Sprague-Dawley rats were employed to determine whether cocaine or cocaine methiodide (CM) administration can induce a significant increase in mean arterial blood pressure (MABP) in rats, and whether such an increase in MABP can produce a global increase in blood oxygenation level-dependent (BOLD) contrast in the rat brain detectable by functional magnetic resonance imaging (fMRI). Cocaine methiodide is a quaternary derivative of cocaine that shares the same cardiovascular effects of cocaine, but does not penetrate the blood-brain barrier (BBB). Experimental results demonstrated that both CM (with doses of 2.5 and 7.5 mg/kg) and cocaine (with doses of 1.25 and 5.0 mg/kg) can induce a significant MABP change (30-80%). It was found that CM can only produce scattered, weak, and transient BOLD signals in a few voxels of the rat brain, and that these MABP-induced BOLD signals are not dose-dependent. In contrast, the administration of cocaine induced dose-dependent biphasic BOLD signals that were consistent with pharmacologically-induced cerebral vascular constriction and neuronal activity in the mesolimbic systems of the rat brain. The potential confounding factor of the MABP changes had little effect on the interpretation of drug-induced BOLD signal changes. These results confirm that the BOLD-weighted fMRI method can be extended to map drug-induced neuronal activity.     

Spatial/temporal correlation of BOLD and optical intrinsic signals in humans.

Comparing the BOLD signal with electrophysiological maps and other perfusion-dependent signals, such as the optical intrinsic signal (OIS), within subjects should provide insight into the etiology of the BOLD signal. Tongue activations were compared in five human subjects using BOLD fMRI, 610-nm OIS, and the electrocortical stimulation map (ESM). Robust fMRI activations centered on the lateral inferior aspect of the central sulcus and extended into pre- and post-central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized, although optical responses were spatially larger (P <.001 across multiple thresholds) and contained more gyral components. The timecourses of the fMRI and OIS signals were similar, appearing within 2.5 s and peaking 6-8 s after task onset. Although many processes contribute to increased 610-nm reflectance, optical spectroscopy and fluorescent dye imaging suggest that a significant part of this signal is due to a concomitant decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the positive 610-nm response within subjects suggests that the two signals may share similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and light-scattering contributions to OIS and fMRI sensitivity. This study also demonstrates that fMRI maps do not precisely colocalize with ESM, rather they emphasize changes in adjacent venous/sulcal structures.     

Functional MRI with magnetization transfer effects: Determination of BOLD and arterial blood volume changes

The primarily intravascular magnetization transfer (MT)‐independent changes in functional MRI (fMRI) can be separated from MT‐dependent changes. This intravascular component is dominated by an arterial blood volume change (ΔCBV_a) term whenever venous contributions are minimized. Stimulation‐induced ΔCBV_a can therefore be measured by a fit of signal changes to MT ratio. MT‐varied fMRI data were acquired in 13 isoflurane‐anesthetized rats during forepaw stimulation at 9.4T to simultaneously measure blood‐oxygenation‐level–dependent (BOLD) and ΔCBV_a response in somatosensory cortical regions. Transverse relaxation rate change (ΔR₂) without MT was –0.43 ± 0.15 s^?1, and MT ratio decreased during stimulation. ΔCBV_a was 0.46 ± 0.15 ml/100 g, which agrees with our previously‐presented MT‐varied arterial‐spin‐labeled data (0.42 ± 0.18 ml/100 g) in the same animals and also correlates with ΔR₂ without MT. Simulations show that ΔCBV_a quantification errors due to potential venous contributions are small for our conditions. Magn Reson Med 60:1518–1523, 2008. © 2008 Wiley‐Liss, Inc.     

Sources of phase changes in BOLD and CBV-weighted fMRI.

Phase changes in blood oxygenation-level dependent (BOLD) fMRI have been observed in humans; however, their exact origin has not yet been fully elucidated. To investigate this issue, we acquired gradient-echo (GE) BOLD and cerebral blood volume (CBV)-weighted fMRI data in anesthetized cats during visual stimulation at 4.7T and 9.4T, before and after injection of a superparamagnetic contrast agent (monocrystalline iron oxide nanoparticles, MION), respectively. In BOLD fMRI, large positive changes in both magnitude and phase were observed predominantly in the cortical surface area, where the large draining veins reside. In CBV-weighted fMRI, large negative changes in both magnitude and phase were detected mainly in the middle cortical area, where the greatest CBV change takes place. Additionally, the phase change was temporally correlated with the magnitude response and was linearly dependent on the echo time (TE), which cannot be explained by the intravascular (IV) contribution and functional temperature change. Phase changes with the opposite polarity were also observed in the regions around the dominant phase changes. These phase changes can be explained by the application of the "Lorentz sphere" theory in the presence of relevant activation-induced changes in vessels. The volume-averaged magnetization and its demagnetization are the main sources of fMRI signal phase change.     

Imaging oxygen consumption in forepaw somatosensory stimulation in rats under isoflurane anesthesia.

The cerebral metabolic rate of oxygen (CMRO2) was dynamically evaluated on a pixel-by-pixel basis in isoflurane-anesthetized and spontaneously breathing rats following graded electrical somatosensory forepaw stimulations (4, 6, and 8 mA). In contrast to alpha-chloralose, which is the most widely used anesthetic in forepaw-stimulation fMRI studies of rats under mechanical ventilation, isoflurane (1.1-1.2%) provided a stable anesthesia level over a prolonged period, without the need to adjust the ventilation volume/rate or sample blood gases. Combined cerebral blood flow signals (CBF) and blood oxygenation level-dependent (BOLD) fMRI signals were simultaneously measured with the use of a multislice continuous arterial spin labeling (CASL) technique (two-coil setup). CMRO2 was calculated using the biophysical BOLD model of Ogawa et al. (Proc Natl Acad Sci USA 1992;89:5951-5955). The stimulus-evoked BOLD percent changes at 4, 6, and 8 A were, respectively, 0.5% +/- 0.2%, 1.4% +/- 0.3%, and 2.0% +/- 0.3% (mean +/- SD, N = 6). The CBF percent changes were 23% +/- 6%, 58% +/- 9%, and 87% +/- 14%. The CMRO2 percent changes were 14% +/- 4%, 24% +/- 6%, and 43% +/- 11%. BOLD, CBF, and CMRO2 activations were localized to the forepaw somatosensory cortices without evidence of plateau for oxygen consumption, indicative of partial coupling of CBF and CMRO2. This study describes a useful forepaw-stimulation model for fMRI, and demonstrate that CMRO2 changes can be dynamically imaged on a pixel-by-pixel basis in a single setting with high spatiotemporal resolution.