Laminar fMRI using T₂-prepared multi-echo FLASH

Functional magnetic resonance imaging (fMRI) using blood oxygenation level dependent (BOLD) contrast at a sub-millimeter scale is a promising technique to probe neural activity at the level of cortical layers. While gradient echo (GRE) BOLD sequences exhibit the highest sensitivity, their signal is confounded by unspecific extravascular (EV) and intravascular (IV) effects of large intracortical ascending veins and pial veins leading to a downstream blurring effect of local signal changes. In contrast, spin echo (SE) fMRI promises higher specificity towards signal changes near the microvascular compartment. However, the T₂-weighted signal is typically sampled with a gradient echo readout imposing additional T₂'-weighting. In this work, we used a T₂-prepared (T₂-prep) sequence with short GRE readouts to investigate its capability to acquire laminar fMRI data during a visual task in humans at 7 T. By varying the T₂-prep echo time (TE_prep) and acquiring multiple gradient echoes (TE_GRE) per excitation, we studied the specificity of the sequence and the influence of possible confounding contributions to the shape of laminar fMRI profiles. By fitting and extrapolating the multi-echo GRE data to a TE_GRE = 0 ms condition, we show for the first time laminar profiles free of T₂'-pollution, confined to gray matter. This finding is independent of TE_prep, except for the shortest one (31 ms) where hints of a remaining intravascular component can be seen. For TE_GRE > 0 ms a prominent peak at the pial surface is observed that increases with longer TE_GRE and dominates the shape of the profiles independent of the amount of T₂-weighting. Simulations show that the peak at the pial surface is a result of static EV dephasing around pial vessels in CSF visible in GM due to partial voluming. Additionally, another, weaker, static dephasing effect is observed throughout all layers of the cortex, which is particularly obvious in the data with shortest T₂-prep echo time. Our simulations show that this cannot be explained by intravascular dephasing but that it is likely caused by extravascular effects of the intracortical and pial veins. We conclude that even for TE_GRE as short as 2.3 ms, the T₂'-weighting added to the T₂-weighting is enough to dramatically affect the laminar specificity of the BOLD signal change. However, the bulk of this corruption stems from CSF partial volume effects which can in principle be addressed by increasing the spatial resolution of the acquisition.