Source of nonlinearity in echo-time-dependent BOLD fMRI.

Stimulation-induced changes in transverse relaxation rates can provide important insight into underlying physiological changes in blood oxygenation level-dependent (BOLD) contrast. It is often assumed that BOLD fractional signal change (DeltaS/S) is linearly dependent on echo time (TE). This relationship was evaluated at 9.4 T during visual stimulation in cats with gradient-echo (GE) and spin-echo (SE) echo-planar imaging (EPI). The TE dependence of GE DeltaS/S is close to linear in both the parenchyma and large vessel area at the cortical surface for TEs of 6-20 ms. However, this dependence is nonlinear for SE studies in the TE range of 16-70 ms unless a diffusion-weighting of b = 200 s/mm(2) is applied. This behavior is not caused by inflow effects, T(2)* decay during data acquisition in SE-EPI, or extravascular spin density changes. Our results are explained by a two-compartment model in which the extravascular contribution to DeltaS/S vs. TE is linear, while the intravascular contribution can be nonlinear depending on the magnetic field strength and TE. At 9.4 T, the large-vessel IV signal can be minimized by using long TE and/or moderate diffusion weighting. Thus, stimulation-induced relaxation rate changes should be carefully determined, and their physiological meanings should be interpreted with caution.