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An automated serial histology setup combining optical coherence tomography (OCT) imaging with vibratome sectioning was used to image eight wild type mouse brains. The datasets resulted in thousands of volumetric tiles resolved at a voxel size of (4.9×4.9×6.5)  μm3 stitched back together to give a three-dimensional map of the brain from which a template OCT brain was obtained. To assess deformation caused by tissue sectioning, reconstruction algorithms, and fixation, OCT datasets were compared to both in vivo and ex vivo magnetic resonance imaging (MRI) imaging. The OCT brain template yielded a highly detailed map of the brain structure, with a high contrast in white matter fiber bundles and was highly resemblant to the in vivo MRI template. Brain labeling using the Allen brain framework showed little variation in regional brain volume among imaging modalities with no statistical differences. The high correspondence between the OCT template brain and its in vivo counterpart demonstrates the potential of whole brain histology to validate in vivo imaging.

Comparing three-dimensional serial optical coherence tomography histology to MRI imaging in the entire mouse brain