Intervoxel heterogeneity of event-related functional magnetic resonance imaging responses as a function of T₁ 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 T₁ weighting (reduced TR, increased FA). The well-known "positive" effect is attributed to in-flow of fresh spins in the slice, leading to an apparent reduction in T₁. 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 T₁ is greater than tissue T₁ (at 1.5 T, the fractional BOLD effect decreases with increased T₁ weighting. To aid in the interpretation of these experimental results, numerical simulations were performed based on a physiological multi-compartment model, including pure tissue, large vessels (arteries, veins), microvessels (arterioles, capillaries, venules), and cerebrospinal fluid.