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

Abstract

An automated dual-resolution serial optical coherence tomography (2R-SOCT) scanner is developed. The serial histology system combines a low-resolution ( $25\mu m/\mathrm{voxel}$ ) $3\times$ OCT with a high-resolution ( $1.5\mu m/\mathrm{voxel}$ ) $40\times$ OCT to acquire whole mouse brains at low resolution and to target specific regions of interest (ROIs) at high resolution. The $40\times$ 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-resolution $40\times$ 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.

Keywords: diffusion MRI; multimodal registration; optical coherence tomography; serial histology; whole mouse brain imaging.