AbstractCortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (<1 mm) in the homologous brain area (hMT+, V5) in living humans by using ultra-high field functional magnetic resonance imaging (fMRI). Despite the reproducibility of the selective response to axis-of-motion stimuli, clear quantitative evidence for the columnar organization of hMT+ is still lacking. Using cerebral blood volume (CBV)-sensitive fMRI at 7 Tesla with submillimeter resolution and high spatial specificity to microvasculature, we investigate the columnar functional organization of hMT+ in 5 participants perceiving axis-of-motion stimuli for both blood oxygenation level dependent (BOLD) and vascular space occupancy (VASO) contrast mechanisms provided by the used slice-selective slab-inversion (SS-SI)-VASO sequence. With the development of a new searchlight algorithm for column detection, we provide the first quantitative columnarity map that characterizes the entire 3D hMT+ volume. Using voxel-wise measures of sensitivity and specificity, we demonstrate the advantage of using CBV-sensitive fMRI to detect mesoscopic cortical features by revealing higher specificity of axis-of-motion cortical columns for VASO as compared to BOLD contrast. These voxel-wise metrics also provide further insights on how to mitigate the highly debated draining veins effect. We conclude that using CBV–VASO fMRI together with voxel-wise measurements of sensitivity, specificity and columnarity offers a promising avenue to quantify the mesoscopic organization of hMT+ with respect to axis-of-motion stimuli. Furthermore, our approach and methodological developments are generalizable and applicable to other human brain areas where similar mesoscopic research questions are addressed.