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.     

Concurrent fMRI and optical measures for the investigation of the hemodynamic response function.

Functional magnetic resonance imaging (fMRI) signal variations are based on a combination of changes in cerebral blood flow (CBF) and volume (CBV), and blood oxygenation. We investigated the relationship between these hemodynamic parameters in the rodent barrel cortex by performing fMRI concurrently with laser Doppler flowmetry (LDF) or optical imaging spectroscopy (OIS), following whisker stimulation and hypercapnic challenge. A difference between the positions of the maximum blood oxygenation level-dependent (BOLD) and CBV changes was observed in coronal fMRI maps, with the BOLD region being more superficial. A 6.5% baseline blood volume fraction in this superficial region dropped to 4% in deeper cortical layers (corresponding to total hemoglobin baseline volumes Hbt0 = 110 microM and 67 microM, respectively), as inferred from maps of deltaR2*. Baseline volume profiles were used to parameterize the Monte Carlo simulations (MCS) to interpret the 2D OIS. From this it was found that the optical blood volume measurements (i.e., changes in total hemoglobin) equated with CBV-MRI measurements when the MRI data were taken from superficial cortical layers. Optical measures of activation showed a good spatial overlap with fMRI measurements taken in the same plane (covering the right hemisphere surface). Changes in CBV and CBF followed the scaling relationship CBV = CBF(alpha), with mean alpha = 0.38 +/- 0.06.     

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.     

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.     

Innovations in functional MR imaging of the brain: arterial spin labeling and diffusion

The standard technique for brain activation functional MRI (fMRI) is the BOLD sequence. Two new techniques have emerged: arterial spin labeling (ASL) MRI and diffusion MRI. Both have the theoretical advantage of more accurately directly demonstrating neuronal activation compared to BOLD imaging, resulting in improved spatial and temporal resolution. ASL is a perfusion sequence using labeled arterial protons as an endogenous perfusion agent. In spite of methodological difficulties, quantitative CBF measurements are possible. ASL is less susceptible to venous contamination than BOLD and more reproducible. Diffusion MRI evaluates neuronal activation at the cellular level with the prospect of excellent spatial resolution. The main limitations for both techniques are the technical difficulties in the acquisition and the low SNR. AS such, ASL is not widely used clinically and diffusion remains in the field of research. However, the increasing availability of 3T MR systems coupled with multi-channel surface coils and improved postprocessing techniques should improve the detection of the brain activation signal. It is thus possible that these techniques could become clinically available either in complement to or as a replacement for BOLD imaging.     

Functional brain imaging using a blood oxygenation sensitive steady state.

Blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an important method for functional neuroimaging that is sensitive to changes in blood oxygenation related to brain activation. While BOLD imaging has good spatial coverage and resolution relative to other neuroimaging methods (such as positron emission tomography (PET)), it has significant limitations relative to other MRI techniques, including poor spatial resolution, low signal levels, limited contrast, and image artifacts. These limitations derive from the coupling of BOLD functional contrast to sources of image degradation. This work presents an alternative method for fMRI that may over-come these limitations by establishing a blood oxygenation sensitive steady-state (BOSS) that inverts the signal from deoxygenated blood relative to the water signal. BOSS fMRI allows the imaging parameters to be optimized independently of the functional contrast, resulting in fewer image artifacts and higher signal-to-noise ratio (SNR). In addition, BOSS fMRI has greater functional contrast than BOLD. BOSS fMRI requires careful shimming and multiple acquisitions to obtain a precise alignment of the magnetization to the SSFP frequency response.     

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.     

Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system.

Several methods are now available for measuring cerebral perfusion and related hemodynamic parameters using magnetic resonance imaging (MRI). One class of techniques utilizes electromagnetically labeled arterial blood water as a noninvasive diffusible tracer for blood flow measurements. The electromagnetically labeled tracer has a decay rate of T1, which is sufficiently long to allow perfusion of the tissue and microvasculature to be detected. Alternatively, electromagnetic arterial spin labeling (ASL) may be used to obtain qualitative perfusion contrast for detecting changes in blood flow, similar to the use of susceptibility contrast in blood oxygenation level dependent functional MRI (BOLD fMRI) to detect functional activation in the brain. The ability to obtain blood flow maps using a non-invasive and widely available modality such as MRI should greatly enhance the utility of blood flow measurement as a means of gaining further insight into the broad range of hemodynamically related physiology and pathophysiology. This article describes the biophysical considerations pertaining to the generation of quantitative blood flow maps using a particular form of ASL in which arterial blood water is continuously labeled, termed continuous arterial spin labeling (CASL). Technical advances permit multislice perfusion imaging using CASL with reduced sensitivity to motion and transit time effects. Interpretable cerebral perfusion images can now be reliably obtained in a variety of clinical settings including acute stroke, chronic cerebrovascular disease, degenerative diseases and epilepsy. Over the past several years, the technical and theoretical foundations of CASL perfusion MRI techniques have evolved from feasibility studies into practical usage. Currently existing methodologies are sufficient to make reliable and clinically relevant observations which complement structural assessment using MRI. Future technical improvements should further reduce the acquisition times for CASL perfusion MRI, while increasing the slice coverage, resolution and stability of the images. These techniques have a broad range of potential applications in clinical and basic research of brain physiology, as well as in other organs.     

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   

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.     

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.     

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.     

Effects of the apparent transverse relaxation time on cerebral blood flow measurements obtained by arterial spin labeling.

Previous modeling studies have predicted that a significant fraction of the signal in arterial spin labeling (ASL) experiments originates from labeled water in the capillaries. Provided that the relaxation times in blood and tissue are similar, ASL data can still be analyzed with the conventional one-compartment Kety model. Such studies have primarily focused on T1 differences and have neglected any differences in transverse relaxation times (T2 and T2*). This is reasonable for studies at lower fields; however, it may not be valid at higher fields due to the stronger susceptibility effects of deoxygenated blood. In this study a tracer kinetic model was developed that includes T2* differences between capillary blood and tissue. The model predicts that a reduction in blood T2* at higher fields will attenuate the capillary contribution to the ASL signal. This in turn causes an underestimation of CBF when ASL data are analyzed with the one-compartment Kety model. We confirmed this prediction by comparing ASL data collected at 1.5 and 4 T, and at multiple gradient echoes (19, 32, 45, and 58 ms). A decrease in resting-state CBF with echo time (TE) was observed at 4 T, but not at 1.5 T. These results suggest that at higher fields AST data should be collected using gradient-echo techniques with short TEs, or with spin-echo techniques. Furthermore, the sensitivity of the CBF measurements to venous T2* may affect the interpretation of concurrent ASL/BOLD studies.     

Simultaneous noninvasive measurement of CBF and CBV using double-echo FAIR (DEFAIR).

A new method for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV) noninvasively using MRI is presented. The approach is based on the technique of arterial spin labelling (ASL), in which CBF-based contrast is generated by controlled modulation of the longitudinal magnetization of the blood. The proposed method also uses differences in T(2) between tissue and blood to differentiate the two compartments and allow assessment of the relative size of each. Two successive EPI images are acquired following spin preparation using either a slice-selective or global inversion pulse, and the technique is therefore referred to as double-echo FAIR (DEFAIR). DEFAIR is demonstrated in the normal gerbil brain and during hypothermia, where reductions of both CBF and CBV are known to occur. It is also shown theoretically that this method can be extended to include a measurement of oxygen extraction fraction. The main drawbacks of the technique are the long acquisition time and relatively low sensitivity to hemodynamic changes compared to conventional qualitative T2(*)-weighted BOLD contrast, which may limit its applicability and practical use in monitoring functional cerebral activation. However, the technique can be used repetitively in longer-term time course studies due to its noninvasive and quantitative nature.     

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.     

Quantifying CBF with arterial spin labeling

The basic principles of measuring cerebral blood flow (CBF) using arterial spin labeling (ASL) are reviewed. The measurement is modeled by treating the ASL method as a magnetic resonance imaging (MRI) version of a microsphere study, rather than a diffusible tracer study. This approach, particularly when applied to pulsed ASL (PASL) experiments, clarifies that absolute calibration of CBF primarily depends on global properties of blood, rather than local tissue properties such as the water partition coefficient or relaxation time. However, transit delays from the tagging region to the image voxel are a potential problem in all standard ASL methods. The key to quantitative CBF measurements that compensate for this systematic error is to create a well-defined bolus of tagged blood and to ensure that all of the bolus has been delivered to an imaging voxel at the time of measurement. Two practical technical factors considered here are 1) producing a tagged bolus with a well-defined temporal width and 2) accounting for reduction in magnitude of the tagged magnetization due to relaxation. The ASL approach has the potential to provide a robust estimation of CBF, although the timing of water exchange into tissue and the effects of pulsatile flow require further investigation.     

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.     

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.     

Anesthetic effects on regional CBF,BOLD, and the coupling between task‐induced changes in CBF and BOLD: An fMRI study in normal human subjects

Functional MR imaging was performed in sixteen healthy human subjects measuring both regional cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) signal when visual and auditory stimuli were presented to subjects in the presence or absence of anesthesia. During anesthesia, 0.25 mean alveolar concentration (MAC) sevoflurane was administrated. We found that low‐dose sevoflurane decreased the task‐induced changes in both BOLD and CBF. Within the visual and auditory regions of interest inspected, both baseline CBF and the task‐induced changes in CBF decreased significantly during anesthesia. Low‐dose sevoflurane significantly altered the task‐induced CBF‐BOLD coupling; for a unit change of CBF, a larger change in BOLD was observed in the anesthesia condition than in the anesthesia‐free condition. Low‐dose sevoflurane was also found to have significant impact on the spatial nonuniformity of the task‐induced coupling. The alteration of task‐induced CBF‐BOLD coupling by low‐dose sevoflurane introduces ambiguity to the direct interpretation of functional MRI (fMRI) data based on only one of the indirect measures—CBF or BOLD. Our observations also indicate that the manipulation of the brain with an anesthetic agent complicates the model‐based quantitative interpretation of fMRI data, in which the relative task‐induced changes in oxidative metabolism are calculated by means of a calibrated model given the relative changes in the indirect vascular measures, usually CBF and BOLD. Magn Reson Med 60:987–996, 2008. © 2008 Wiley‐Liss, Inc.     

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.