- The vast majority of information that neuroscience has obtained about the microscopic structure of the human brain ? the substrate for cognitive competencies and the specific locations of neuropathological processes ? has been obtained by the analysis of ex vivo tissue. Historically this involves the decades (if not centuries) old procedure of cutting, staining, mounting and imaging under a microscope. The last two decades have seen stunning advances in imaging and analysis of the human brain. This include advances in microscopic (e.g. CLARITY1, SWITCH), mesoscopic (e.g., polarized light imaging, PLI), optical coherence tomography (OCT), RNA-seq and macroscopic imaging (e.g., MRI). While these techniques have generated huge amounts of new information regarding the structural, molecular, connectomic, genetic and transcriptional nature of the brain, they have thus far had little impact on in vivo analysis. In the same way, while we have made great progress in our ability to localize important brain regions in living subjects, these capabilities have had little impact in microscopy and neuropathology. In this project we seek to use our mesoscopic imaging and analysis tools to remove these barriers and facilitate the flow of information from microscopy to in vivo human studies, as well as in the reverse direction. Examples of the impact of these new abilities would be: using resting-state fMRI networks (rsFMRI) to guide the extraction of neuropathological blocks during autopsy to test network-based theories of various neurodegenerative disease or using predicted vascular distributions and densities to improve the laminar specificity of fMRI.
