A method is presented for three-dimensional reconstruction of the mouse brain from histological sections with the guidance of magnetic resonance images (MRI). A major focus of the method is dealing with sections in which anatomical structures have been separated or distorted as a result of histological processing. Although histology has superb resolution with the ability to discriminate cell types and anatomical structures, misalignment between sections and distortion within sections renders 3D reconstruction of the histology volume simply by stacking 2D sections inadequate. In contrast, MRI preserves the spatial and geometric information about structures at a cost of cellular detail. To utilize the information from MRI in reconstructing volumetric histological data, we developed a procedure consisting of a series of segmentation and registration operations. The method is iterative and first identifies the corresponding MRI slices for each histological section. Piecewise rigid registration is then employed to deal with tissue distortion caused by histological processing. Quantitative validation of the method's accuracy was performed on four reconstructed mouse brains by comparing a set of manually selected anatomical landmarks on pairs of MRI and histological volumes. The procedure is highly automated and amenable to high throughput.
Copyright © 2012 Elsevier B.V. All rights reserved.