Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques

Abstract

Purpose: To compare cerebrovascular reactivity (CVR) quantified with pseudo-continuous arterial spin labeling (pCASL) and blood oxygen level dependent (BOLD) fMRI techniques.

Materials and methods: Sixteen healthy volunteers (age: 37.8±14.3years; 6 women and 10 men; education attainment: 17±2.1years) were recruited and completed a 5% CO2 gas-mixture breathing paradigm at 3T field strength. ASL and BOLD images were acquired for CVR determination assuming that mild hypercapnia does not affect the cerebral metabolic rate of oxygen. Both CVR quantifications were derived as the ratio of the fractional cerebral blood flow (CBF) or BOLD signal change over the change in end-tidal CO2 pressure.

Results: The absolute CBF, BOLD and CVR measures were consistent with literature values. CBF derived CVR was 5.11±0.87%/mmHg in gray matter (GM) and 4.64±0.37%/mmHg in parenchyma. BOLD CVR was 0.23±0.04%/mmHg and 0.22±0.04%/mmHg for GM and parenchyma respectively. The most significant correlations between BOLD and CBF-based CVRs were also in GM structures, with greater vascular response in occipital cortex than in frontal and parietal lobes (6.8%/mmHg versus 4.5%/mmHg, 50% greater). Parenchymal BOLD CVR correlated significantly with the fractional change in CBF in response to hypercapnia (r=0.61, P=0.01), suggesting the BOLD response to be significantly flow driven. GM CBF decreased with age in room air (-5.58mL/100g/min per decade for GM; r=-0.51, P=0.05), but there was no association of CBF with age during hypercapnia. A trend toward increased pCASL CVR with age was observed, scaling as 0.64%/mmHg per decade for GM.

Conclusion: Consistent with previously reported CVR values, our results suggest that BOLD and CBF CVR techniques are complementary to each other in evaluating neuronal and vascular underpinning of hemodynamic processes.

Keywords: Arterial spin labeling; BOLD; Cerebral blood flow; Cerebrovascular reactivity; Hypercapnia-based fMRI calibration; Neurovascular coupling.

Figure 1

Experimental paradigm of sequential BOLD and pCASL acquisitions. The whole experiment, including subject setting and other MRI scans before CVR quantification such as phase-contrast MRI and 3D T1 for global CBF measurements, took about 45 minutes.

Figure 2

A: Significant correlation between average GM CBF and P_ETCO2 at baseline room air condition in control subjects (r=0.55, P=0.027). B: Significant correlation between average parenchymal CBF percentage change and change of P_ETCO2 (ΔP_ETCO2) at hypercapnia from room air (baseline) condition in healthy control subjects (r=0.70, P<0.005). The dashed lines represent 95% lower and upper confidence intervals of the linear correlation.

Figure 3

Group average of CBF in MNI space at baseline (room air, A1) and hypercapnia (A2). The absolute difference of average CBF map comparing hypercapnia to baseline was shown in A3. CBF was elevated significantly in most cerebral areas during hypercapnia than in room air (A3). B1: Group average of CBF derived CVR (in %/mmHg) calculated as fractional CBF change during hypercapnia relative to P_ETCO2 change. B2: Group-wise 1-sample paired t-test of pCASL CVRs showing consistent large clusters of significant CBF changes (i.e. CVR) across subject, in somatosensory, occipital, temporal, parietal and frontal regions after application of a comprehensive threshold with family-wise error (FWE) correction (T>6.29 and cluster size K>5).

Figure 4

A: Quantitative pCASL-based average CBF in room air (baseline) and hypercapnia, for the whole brain (WB) parenchyma and gray matter (GM). CBF values were obtained by averaging over each tissue type with an empirical minimum threshold of 10% of maximum of the whole brain. During hypercapnia, the CBF in whole brain and gray matter was significantly higher than CBF at baseline, with an approximately 40% increase, as shown in the rightmost column in A. B: Average pCASL CVR in gray matter and whole brain parenchyma across subject.

Figure 5

Time course of BOLD signal changes in response to a hypercapnic challenge interleaved with room air and averaged in the brain regions over three contiguous slices (slices centered at the thalamus) of a representative subject (A). The delay (i.e. latency) that best matched the BOLD signal to P_ETCO2 was obtained by shifting the P_ETCO2 signal to maximize the correlation between the two signals. B: Histogram of maximal correlation coefficient showing good match between BOLD and P_ETCO2 with an average of 0.9 for all subjects. C: Histogram of latency between BOLD and P_ETCO2 signal in all subjects, with an average delay of 6 seconds (including correction for the exhaled CO₂ to reach the capnometer).

Figure 6

A: Group average of BOLD CVR (%/mmHg) parametric images obtained using shifted resampled P_ETCO2 as a reference function with general linear model. B: Smoothed 3D volume-rendered sagittal view (1 sample t-test, family wise error corrected P<0.05). C: Average whole-brain BOLD GM and parenchymal CVR.

Figure 7

A: Significant correlation between fractional percentage change in CBF in response to hypercapnia and BOLD CVR (r=0.61, P=0.01) in parenchyma. B: A trend of positive correlation between two parenchymal CVRs after P_ETCO2 normalization (r=0.43, P=0.09).

Figure 8

A: Voxel-wise correlation between pCASL and BOLD CVR (minimum Z > 2; cluster level, P <0.05, corrected by Gaussian random field theory) using non-linear (2^nd order polynomial) correlation after high-order detrending. B: Regional data, displayed after scaling BOLD CVR by a factor of 22 to match average pCASL CVR. Note: bilateral lobar and sub-regional areas were defined with well-established parcellations by combining BA regions. Frontal cortex = BAs 4, 6, 8, 9, 10, 11, 44, 45; Motor region = BAs 4, 6 and 8; Prefrontal region = BAs 9, 10, 11; Broca's area = BAs 44, 45. Parietal cortex = BAs 1, 2, 3, 5, 7, 39, 40; Somatosensory area = BAs 1, 2, 3. Temporal cortex = BAs 21, 22, 41, 42, 37; Wernicke's area =BAs 21, 22, 42. Visual cortex = BAs 17, 18, 19. Subcortical area =caudate, thalamus, putamen, pallidum, hippocampus, amygdala, accumbens and brainstem. Left and right hemisphere contain combined lateral BA regions from four lobes specified.

Figure 9

Association between average gray-matter (GM) pCASL CVR and subject age (r=0.55, P=0.044) after excluding two subjects with GM CVR values out of the range of one standard deviation from the group mean of GM CVR.