Mixed methodology to map the human subcortex

Over 90% of the individual brain areas residing in the human subcortex are currently still missing from MRI-atlases. As a result these approximately 400 structures are being systematically overlooked in scientific literature. To help close the knowledge gap we have created both in vivo and post mortem approaches to improve the available anatomical tools to study the subcortex. Using 7 Tesla (functional) MRI at submillimeter resolutions in vivo, so far we have mapped the development of 35 individual subcortical brain structures across the adult lifespan (age 18-80y), revealing location shifts and iron accumulation with increasing age. Despite the availability of submillimeter resolution MRI data, many subcortical structures remain too small to visualize in vivo. The same holds for the detailed mapping of the microvasculature. Therefore, we have developed a brain processing pipeline that provides higher anatomical detail through combining post mortem MRI and microscopy approaches. MRI-scanned tissue was processed for microscopy studies. The created detailed digital 3D reconstructions have been coregistered with the MRI scans and provide a resource that allows the mapping of smaller subcortical brain structures. These efforts together represent an incremental brain atlasing project in which data from different imaging modalities is combined in a shared 3-dimensional space. The exploration of these combined data now provide new insights in the location and volume of previously overlooked structures.