BOLD‐specific cerebral blood volume and blood flow changes during neuronal activation in humans

Abstract

To understand and predict the blood-oxygenation level-dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (DeltaCBF) and volume (DeltaCBV) changes is critical. Currently, this relationship is widely assumed to be characterized by Grubb's power-law, derived from primate data, where the power coefficient (alpha) was found to be 0.38. The validity of this general formulation has been examined previously, and an alpha of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (DeltaCMRo(2)) using calibrated BOLD. However, the direct use of this relationship has been the subject of some debate, since it is well established that the BOLD signal is primarily modulated by changes in 'venous' CBV (DeltaCBV(v), comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet DeltaCBV(v) measurements in humans have been extremely scarce. In this work, we demonstrate reproducible DeltaCBV(v) measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady-state DeltaCBV(v) and DeltaCBF measurements in human subjects undergoing graded visual and sensorimotor stimulation. We found that: (1) a BOLD-specific flow-volume power-law relationship is described by alpha = 0.23 +/- 0.05, significantly lower than Grubb's constant of 0.38 for total CBV; (2) this power-law constant was not found to vary significantly between the visual and sensorimotor areas; and (3) the use of Grubb's value of 0.38 in gradient-echo BOLD modeling results in an underestimation of DeltaCMRo(2).

Improved fMRI calibration: Precisely controlled hyperoxic versus hypercapnic stimuli

“…In our study, assuming a lower α (value of 0.20 instead of 0.38) reduces hypercapnic M Group_HCP -values by 13-14% across all ROI (i.e., 6.3 ± 0.6%, 5.5 ± 0.7% and 5.0 ± 0.7% in WB, VC and MC, respectively). This is in agreement with the published results of a 12-17% decrease in hypercapnia-induced M-values in VC and MC under smaller α (value of 0.23 instead of 0.38) (Chen and Pike, 2009a). The magnitudes of our M Group -values showed a trend (p = 0.05 in VC and p = 0.08 in MC, paired one-tailed Student's t-test) to higher values (~15-24%) under hypercapnic compared to hyperoxic stimulation when the original α of 0.38 was used (Tables 3A and 3B).…”

“…Having made these arguments on the advantages of using HO for calibration, it is also quite possible that the effect of α-uncertainties in the calculation of M-values based on HC may cancel out in the calculation of ΔCMRO 2 under neuronal activation, as α also directly impacts these estimates for each brain region (Ances et al, 2008;Chen and Pike, 2009a). The extent of this cancellation effect is unclear as the physiological mechanisms involved in local vasodilation in response Fig.…”

“…(1), which accounts for the relative change in blood volume versus blood flow that occurs with hypercapnic provocations, was assumed to have a value of 0.38 (Grubb et al, 1974). Recent studies reported on a lower α-value reflecting only venous rather than total volume changes under neuronal activation (α = 0.23 (Chen and Pike, 2009a)) and likewise under hypercapnia and hypocapnia (α = 0.19 (Chen and Pike, 2009b)), a similarity in α-value across challenge type also seen in PET studies (Ito et al, 2003(Ito et al, , 2001. In our study, assuming a lower α (value of 0.20 instead of 0.38) reduces hypercapnic M Group_HCP -values by 13-14% across all ROI (i.e., 6.3 ± 0.6%, 5.5 ± 0.7% and 5.0 ± 0.7% in WB, VC and MC, respectively).…”

Temporal Dynamics and Spatial Specificity of Arterial and Venous Blood Volume Changes during Visual Stimulation: Implication for Bold Quantification

“…Our finding may explain the substantial DCBV v increase with 96 to 240 seconds long visual stimulation in humans (Chen and Pike, 2009;Stefanovic and Pike, 2005), and venous dilation during the 120-second long direct electric stimulation in halothane-anesthetized rats (Akgoren and Lauritzen, 1999).…”

Developmental trajectories of cerebral blood flow and oxidative metabolism at baseline and during working memory tasks

“…where fBOLD and fCBF are the fractional changes in BOLD and CBF data respectively, and α = 0.2, β = 1.3 (Chen and Pike, 2009). The calibration constant M is usually estimated using a hypercapnia experiment which is not feasible in our pediatric population.…”