Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T (original) (raw)
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NeuroImage, 2006
Spatial specificity of functional magnetic resonance imaging (fMRI) signals to sub-millimeter functional architecture remains controversial. To investigate this issue, high-resolution fMRI in response to visual stimulus was obtained in isoflurane-anesthetized cats at 9.4 T using conventional gradient-echo (GE) and spin-echo (SE) techniques; blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV)-weighted data were acquired without and with injection of 10 mg Fe/kg monocrystalline iron oxide nanoparticles (MION), respectively. Studies after MION injection at two SE times show that the T 2 V contribution to SE fMRI is minimal. GE and SE BOLD changes were spread across the cortical layers. GE and SE CBV-weighted fMRI responses peaked at the middle cortical layer, which has the highest experimentally-determined microvascular volume; full-width at halfmaximum was <1.0 mm. Parenchymal sensitivity of GE CBV-weighted fMRI was¨3 times higher than that of SE CBV-weighted fMRI and 1.5 times higher than that of BOLD fMRI. It is well known that GE CBV-weighted fMRI detects a volume change in vessels of all sizes, while SE CBV-weighted fMRI is heavily weighted toward microvascular changes. Peak CBV change of 10% at the middle of the cortex in GE measurements was 1.8 times higher than that in SE measurements, indicating that CBV changes occur predominantly for vasculature connecting the intracortical vessels and capillaries. Our data supports the notion of laminar-dependent CBV regulation at a sub-millimeter scale. D
Vascular dynamics and BOLD fMRI: CBF level effects and analysis considerations
Neuroimage, 2006
Changes in the cerebral blood flow (CBF) baseline produce significant changes to the hemodynamic response. This work shows that increases in the baseline blood flow level produce blood oxygenation-level dependent (BOLD) and blood flow responses that are slower and lower in amplitude, while decreases in the baseline blood flow level produce faster and higher amplitude hemodynamic responses. This effect was characterized using a vascular model of the hemodynamic response that separated arterial blood flow response from the venous blood volume response and linked the input stimulus to the vascular response. The model predicted the baseline blood flow level effects to be dominated by changes in the arterial vasculature. Specifically, it predicted changes in the arterial blood flow time constant and venous blood volume time constant parameters of +294% and À24%, respectively, for a 27% increase in the baseline blood flow. The vascular model performance was compared to an empirical model of the hemodynamic response. The vascular and empirical hemodynamic models captured most of the baseline blood flow level effects observed and can be used to correct for these effects in fMRI data. While the empirical hemodynamic model is easy to implement, it did not incorporate any explicit physiological information. D
Development of BOLD signal hemodynamic responses in the human brain
NeuroImage, 2012
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Abstract Functional magnetic resonance imaging (fMRI) techniques in which the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) response to a neural stimulus are measured, can be used to estimate the fractional increase in the cerebral metabolic rate of oxygen consumption (CMRO2) that accompanies evoked neural activity. A measure of neurovascular coupling is obtained from the ratio of fractional \{CBF\} and \{CMRO2\} responses, defined as n, with the implicit assumption that relative rather than absolute changes in \{CBF\} and \{CMRO2\} adequately characterise the flow-metabolism response to neural activity. The coupling parameter n is important in terms of its effect on the \{BOLD\} response, and as potential insight into the flow-metabolism relationship in both normal and pathological brain function. In 10 healthy human subjects, \{BOLD\} and \{CBF\} responses were measured to test the effect of baseline perfusion (modulated by a hypercapnia challenge) on the coupling parameter n during graded visual stimulation. A dual-echo pulsed arterial spin labelling (PASL) sequence provided absolute quantification of \{CBF\} in baseline and active states as well as relative \{BOLD\} signal changes, which were used to estimate \{CMRO2\} responses to the graded visual stimulus. The absolute \{CBF\} response to the visual stimuli were constant across different baseline \{CBF\} levels, meaning the fractional \{CBF\} responses were reduced at the hyperperfused baseline state. For the graded visual stimuli, values of n were significantly reduced during hypercapnia induced hyperperfusion. Assuming the evoked neural responses to the visual stimuli are the same for both baseline \{CBF\} states, this result has implications for fMRI studies that aim to measure neurovascular coupling using relative changes in CBF. The coupling parameter n is sensitive to baseline CBF, which would confound its interpretation in fMRI studies where there may be significant differences in baseline perfusion between groups. The absolute change in CBF, as opposed to the change relative to baseline, may more closely match the underlying increase in neural activity in response to a stimulus.
Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI
Magnetic Resonance in Medicine, 2002
The transient relationship between arterial cerebral blood flow (CBFA) and total cerebral blood volume (CBVT) 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% CO2 ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBVT 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 CBVT and CBFA under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBVT and CBFA is region-specific. Voxels with ≥15% BOLD signal changes from hypercapnia (7.5% CO2 ventilation) have a larger power index (α = 3.26), a larger maximum possible BOLD response (M = 0.85), and shorter T (32 ms) caused by deoxyhemoglobin, compared to voxels with <15% BOLD signal changes (α = 1.82, M = 0.16, and T = 169 ms). It is suggested that the biophysical model of the BOLD signal can be extended under the transient state, with a caution that α 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. Magn Reson Med 48:987–993, 2002. © 2002 Wiley-Liss, Inc.
Multi-Echo Investigations of Positive and Negative CBF and Concomitant BOLD Changes
Unlike the positive blood oxygenation level-dependent (BOLD) response (PBR), commonly taken as an indication of an ‘activated’ brain region, the physiological origin of negative BOLD signal changes (i.e. a negative BOLD response, NBR), also referred to as ‘deactivation’ is still being debated. In this work, an attempt was made to gain a better understanding of the underlying mechanism by obtaining a comprehensive measure of the contributing cerebral blood flow (CBF) and its relationship to the NBR in the human visual cortex, in comparison to a simultaneously induced PBR in surrounding visual regions. To overcome the low signal-to-noise ratio (SNR) of CBF measurements, a newly developed multi-echo version of a center-out echo planar-imaging (EPI) readout was employed with pseudo-continuous arterial spin labeling (pCASL). It achieved very short echo and inter-echo times and facilitated a simultaneous detection of functional CBF and BOLD changes at 3 T with improved sensitivity. Evalua...
Dynamic and static contributions of the cerebrovasculature to the resting-state BOLD signal
2014
Functional magnetic resonance imaging (fMRI) in the resting state, particularly fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been extensively used to measure functional connectivity in the brain. However, the mechanisms of vascular regulation that underlie the BOLD fluctuations during rest are still poorly understood. In this work, using dual-echo pseudo-continuous arterial spin labeling and MR angiography (MRA), we assess the spatiotemporal contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and explore how the coupling of these signals is associated with regional vasculature. Using a general linear model analysis, we found that statistically significant coupling between resting-state BOLD and CBF fluctuations is highly variable across the brain, but the coupling is strongest within the major nodes of established resting-state networks, including the default-mode, visual, and task-positive networks. Moreover, by exploiting MRA-derived large vessel (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling significantly decreased as the ratio of large vessels to tissue volume increased. These findings suggest that the portion of resting-state BOLD fluctuations at the sites of medium-to-small vessels (more proximal to local neuronal activity) is more closely regulated by dynamic regulations in CBF, and that this CBF regulation decreases closer to large veins, which are more distal to neuronal activity.
Stimulus-dependent BOLD and perfusion dynamics in human V1
1999
Blood oxygenation level-dependent (BOLD) fMRI signals often exhibit pronounced over-or undershoot upon changes in stimulation state. Current models postulate that this is due to the delayed onset or decay of perfusion-dependent attenuating responses such as increased cerebral blood volume or oxygen consumption, which are presumed to lag behind the rapid adjustment of blood flow rate to a new steady-state level.
Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO 2 ) in this NBR region. The ΔCMRO 2 /ΔCBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n = 0.91 ± 0.04, M = 10.45%) than in the contralateral S1/M1 (n = 0.65 ± 0.03, M = 10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO 2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR.