Abstract
BACKGROUND: Brain mapping research in most neuroanatomical laboratories relies on conventional processing techniques, which often introduce histological artifacts such as tissue tears and tissue loss. NEW METHOD: In this paper, we present techniques and algorithms for automatic registration and 3D reconstruction of conventionally produced mouse brain slices in a standardized atlas space. This is achieved first by constructing a virtual 3D mouse brain model from annotated slices of Allen Reference Atlas (ARA). Virtual re-slicing of the reconstructed model generates ARA-based slice images corresponding to the microscopic images of histological brain sections. These image pairs are aligned using a geometric approach through contour images. Histological artifacts in the microscopic images are detected and removed using Constrained Delaunay Triangulation before performing global alignment. Finally, non-linear registration is performed by solving Laplace's equation with Dirichlet boundary conditions. RESULTS: Our methods provide significant improvements over previously reported registration techniques for the tested slices in 3D space, especially on slices with significant histological artifacts. Further, as one of the application we count the number of neurons in various anatomical regions using a dataset of 51 microscopic slices from a single mouse brain. COMPARISON WITH EXISTING METHOD(S): To the best of our knowledge the presented work is the first that automatically registers both clean as well as highly damaged high-resolutions histological slices of mouse brain to a 3D annotated reference atlas space. CONCLUSIONS: This work represents a significant contribution to this subfield of neuroscience as it provides tools to neuroanatomist for analyzing and processing histological data.