Robust registration of Mouse brain slices with severe histological artifacts

Brain mapping research is facilitated by first aligning digital images of mouse brain slices to standardized atlas framework such as the Allen Reference Atlas (ARA). However, conventional processing of these brain slices introduces many histological artifacts such as tears and missing regions in the tissue, which make the automatic alignment process extremely challenging. We present an end-to-end fully automatic registration pipeline for alignment of digital images of mouse brain slices that may have histological artifacts, to a standardized atlas space. We use a geometric approach where we first align the bounding box of convex hulls of brain slice contours and atlas template contours, which are extracted using a variant of Canny edge detector. We then detect the artifacts using Constrained Delaunay Triangulation (CDT) and remove them from the contours before performing global alignment of points using iterative closest point (ICP). This is followed by a final non-linear registration by solving the Laplace's equation with Dirichlet boundary conditions. We tested our algorithm on 200 mouse brain slice images including slices acquired from conventional processing techniques having major histological artifacts, and from serial two-photon tomography (STPT) with no major artifacts. We show significant improvement over other registration techniques, both qualitatively and quantitatively, in all slices especially on slices with significant histological artifacts.