Abstract While histology remains the gold standard for assessing human neuroanatomy, the procedures for sectioning and hand mounting tissue for microscopic imaging are not substantially different than they were 100 years ago. These steps introduce irremediable distortions into the tissue sections making it difficult or impossible to align sections with suffiient accuracy to create 3D histological volumes at the micron scale. In this project, we seek to develop acquisition and analysis tools that use optical coherence tomography (OCT) to generate images that contain information comparable to standard histology. Critically, OCT images the tissue prior to cutting, thus avoiding the concomitant distortions, and allowing large regions of human tissue to be imaged with micron resolution. We anticipate that these large-scale, veridical representations will facilitate the development of automated techniques for tissue quantification and disease detection, dramatically increasing the efficiency, specificity an sensitivity of histology and neuropathology.