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

To understand and predict the blood‐oxygenation level‐dependent (BOLD) fMRI signal, an accurate knowledge of the relationship between cerebral blood flow (ΔCBF) and volume (ΔCBV) 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 (α) was found to be 0.38. The validity of this general formulation has been examined previously, and an α of 0.38 has been frequently cited when calculating the cerebral oxygen metabolism change (ΔCMRo2) 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 (ΔCBVv, comprising deoxygenated blood in the capillary, venular, and to a lesser extent, in the arteriolar compartments) instead of total CBV, and yet ΔCBVv measurements in humans have been extremely scarce. In this work, we demonstrate reproducible ΔCBVv measurements at 3 T using venous refocusing for the volume estimation (VERVE) technique, and report on steady‐state ΔCBVv and ΔCBF 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 α = 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 ΔCMRo2. Copyright © 2009 John Wiley & Sons, Ltd. A BOLD‐specific CBF‐CBV power‐law relationship is described by α = 0.23 ± 0.05 (c), significantly lower than Grubb's constant of 0.38 for total CBV. This power‐law constant was not found to vary significantly between the visual (a) and sensorimotor (b) areas. The use of Grubb's value of 0.38 in gradient‐echo BOLD modelling results in a significant ΔCMRo2 underestimation.