Whole mouse brain imaging using optical coherence tomography: reconstruction, normalization, segmentation, and comparison with diffusion MRI.

An automated massive histology setup combined with an optical coherence tomography (OCT) microscope was used to image a total of [Formula: see text] whole mouse brains. Each acquisition generated a dataset of thousands of OCT volumetric tiles at a sampling resolution of [Formula: see text]. This paper describes techniques for reconstruction and segmentation of the sliced brains. In addition to the measured OCT optical reflectivity, a single scattering photon model was used to compute the attenuation coefficients within each tissue slice. Average mouse brain templates were generated for both the OCT reflectivity and attenuation contrasts and were used with an [Formula: see text]-tissue segmentation algorithm. To better understand the brain tissue OCT contrast origin, one of the mouse brains was acquired using dMRI and coregistered to its corresponding assembled brain. Our results indicate that the optical reflectivity in a fiber bundle varies with its orientation, its fiber density, and the number of fiber orientations it contains. The OCT mouse brain template generation and coregistration to dMRI data demonstrate the potential of this massive histology technique to pursue cross-sectional, multimodal, and multisubject investigations of small animal brains.