Contributions of dynamic venous blood volume versus oxygenation level changes to BOLD fMRI

Blood-oxygenation-level-dependent (BOLD) fMRI has contributions from venous oxygenation and venous cerebral blood volume (CBV) changes. To examine the relative contribution of venous CBV change (ΔCBVv) to BOLD fMRI, BOLD and arterial CBV changes (ΔCBVa) to a 40-s forepaw stimulation in six α-chloralose anesthetized rats were measured using a magnetization transfer-varied fMRI technique, while total CBV change (ΔCBVt) was measured with injection of iron oxide nanoparticles. ΔCBVv was obtained by subtracting ΔCBVa from ΔCBVt. We observed a fast ΔCBVa response with a time constant of 2.9 ± 2.3 s and a slower ΔCBVv response with a time constant of 13.5 ± 5.7 s and an onset delay of 6.1 ± 3.3 s. These results are consistent with earlier studies under different anesthesia and stimulus, supporting that fast CBVa and slow CBVv responses are generalizable. Assuming the observed post-stimulus BOLD undershoot is at least partly explained by the ΔCBVv contribution, the relative contribution of the ΔCBVv- and oxygenation-change-related components to the BOLD response was estimated. The relative ΔCBVv contribution increases with time during stimulation; whereby it is < 0.14 during initial 10 s and reaches a maximum possible value of ~ 0.45 relative to the oxygenation contribution during the 30–40 s period after stimulus onset. Our data indicates that the contribution of venous oxygenation change to BOLD fMRI is dominant for short stimulations.

► The dynamic venous CBV and oxygenation change induced BOLD responses were studied.
► The venous CBV contribution (ΔCBVv) increases with time during stimulation.
► ΔCBVv can maximally reduce BOLD by 45% during 30–40 s after stimulus onset.
► Fast arterial CBV and slow venous CBV responses were observed.