Intervoxel heterogeneity of event-related functional magnetic resonance imaging responses as a function of T(1) weighting.

Inflow effects on activation-related BOLD signal changes in event-related fMRI experiments were assessed by varying the repetition time (TR) and flip angle (FA) values for gradient-echo echo-planar imaging (GE-EPI). Surprisingly, both increases and decreases were detected in these signal changes with increased T(1) weighting (reduced TR, increased FA). The well-known "positive" effect is attributed to inflow of fresh spins in the slice, leading to an apparent reduction in T(1). The "negative" effect is attributed to voxels containing pure parenchyma, where large-vessel inflow effects are very small and the BOLD effect is dominated by microvascular blood volume and oxygenation changes. Because blood T(1) is greater than tissue T(1) at 1.5 T, the fractional BOLD effect decreases with increased T(1) weighting. To aid in the interpretation of these experimental results, numerical simulations were performed based on a physiological multicompartment model, including pure tissue, large vessels (arteries, veins), microvessels (arterioles, capillaries, venules), and cerebrospinal fluid.