Impact of Prospective Motion Correction, Distortion Correction Methods, and Large Vein Bias on the Spatial Accuracy of Cortical Laminar fMRI at 9.4 Tesla

Depth and large vein distance dependent BOLD responses. (a) Only a small gradient in signal amplitude across cortical depths is visible for iso-vessel distant voxels. Beside a slightly shorter response duration at larger vessel distances a reduction in post-stimulus undershoot can be observed. After reordering the plots to assess the vessel distance dependency within each depth, an even stronger increase in response amplitude near segmented vessels becomes visible (b).
An increasing number of studies aim to perform functional MRI measurements acquired at ultra-high field (UHF) with voxel dimensions in the sub-millimeter scale. Such studies are possible primarily due to the stronger BOLD effect at higher fields, resulting in an increased contrast-to-noise ratio (CNR) in fMRI, as well as the superlinear increase of image signal-to-noise ratio with field strength. The enhanced resolution afforded by these sensitivity gains allows detailed investigation of the BOLD response in varying depths of cortical gray matter, which has rapidly developed to a new field of research. Although the spatial resolution is still too coarse to be actually capable of resolving individual cytoarchitectonically defined cortical layers, this is often referred to ‘laminar’ or ‘depth-dependent’ fMRI and aims for a better understanding of the role of individual cortical layers in, for example, feed-forward and feed-back processing. Smaller voxel dimensions additionally help to differentiate between macro- and microvascular signal sources due to reduced partial volume effects and physiological noise contributions. As voxels become smaller, the heterogeneity of vessel sizes within a given voxel decreases, which can allow for a better understanding of how the different stages of the vascular hierarchy contribute to the observed fMRI signal.
However, several studies have shown that measurement of laminar fMRI responses can be biased by the image acquisition and data processing strategies. In this work, measurements with three different gradient-echo EPI BOLD fMRI protocols with a voxel size down to 650 μm isotropic were performed at 9.4 T. We estimated how prospective motion correction can help to improve spatial accuracy by reducing the number of spatial resampling steps in postprocessing. In addition, we demonstrate key requirements for accurate geometric distortion correction to ensure that distortion correction maps are properly aligned to the functional data and that strong variations of distortions near large veins can lead to signal overlays which cannot be corrected for during postprocessing. Furthermore, this study illustrates the spatial extent of bias induced by pial and other larger veins in laminar BOLD experiments. Since these issues under investigation affect studies performed with more conventional spatial resolutions, the methods applied in this work may also help to improve the understanding of the BOLD signal more broadly.