Submillimeter fMRI Acquisition Techniques for Detection of Laminar and Columnar Level Brain Activation.

Since the first demonstration in the early 1990s, functional MRI (fMRI) has emerged as one of the most powerful, noninvasive neuroimaging tools to probe brain functions. Subsequently, fMRI techniques have advanced remarkably, enabling the acquisition of functional signals with a submillimeter voxel size. This innovation has opened the possibility of investigating subcortical neural activities with respect to the cortical depths or cortical columns. For this purpose, numerous previous works have endeavored to design suitable functional contrast mechanisms and dedicated imaging techniques. Depending on the choice of the functional contrast, functional signals can be detected with high sensitivity or with improved spatial specificity to the actual activation site, and the pertaining issues have been discussed in a number of earlier works. This review paper primarily aims to provide an overview of the subcortical fMRI techniques that allow the acquisition of functional signals with a submillimeter resolution. Here, the advantages and disadvantages of the imaging techniques will be described and compared. We also summarize supplementary imaging techniques that assist in the analysis of the subcortical brain activation for more accurate mapping with reduced geometric deformation. This review suggests that there is no single universally accepted method as the gold standard for subcortical fMRI. Instead, the functional contrast and the corresponding readout imaging technique should be carefully determined depending on the purpose of the study. Due to the technical limitations of current fMRI techniques, most subcortical fMRI studies have only targeted partial brain regions. As a future prospect, the spatiotemporal resolution of fMRI will be pushed to satisfy the community's need for a deeper understanding of whole-brain functions and the underlying connectivity in order to achieve the ultimate goal of a time-resolved and layer-specific spatial scale. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.