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.  An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution (    25      μ  m  /  voxel    )3  ×OCT with a high-resolution (    1.5      μ  m  /  voxel    )40  ×OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The40  ×ROIs positions are selected either manually by the microscope operator or using an automated ROI positioning selection algorithm. Additionally, a multimodal and multiresolution registration pipeline is developed in order to align the 2R-SOCT data onto diffusion MRI (dMRI) data acquired in the same  ex vivo  mouse brains prior to automated histology. Using this imaging system, 3 whole mouse brains are imaged, and 250 high-resolution40  ×three-dimensional ROIs are acquired. The capability of this system to perform multimodal imaging studies is demonstrated by labeling the ROIs using a mouse brain atlas and by categorizing the ROIs based on their associated dMRI measures. This reveals a good correspondence of the tissue microstructure imaged by the high-resolution OCT with various dMRI measures such as fractional anisotropy, number of fiber orientations, apparent fiber density, orientation dispersion, and intracellular volume fraction.

Fully automated dual-resolution serial optical coherence tomography aimed at diffusion MRI validation in whole mouse brains