Co-registration of in vivo human MRI brain images to postmortem histological microscopic images

Certain features such as small vascular lesions seen in human MRI (Magnetic Resonance Imaging) are detected reliably only in postmortem histological samples by microscopic imaging. Coregistration of these microscopically detected features to their corresponding locations in the in vivo images would be of great benefit to understanding the MRI signatures of specific diseases. Using nonlinear Polynomial transformation, we report a method to co-register in vivo MRIs to microscopic images of histological samples drawn off the postmortem brain. The approach utilizes digital photographs of postmortem slices as an intermediate reference to co-register the MRIs to microscopy. The overall procedure is challenging due to gross structural deformations in the postmortem brain during extraction and subsequent distortions in the histological preparations. Hemispheres of the brain were co-registered separately to mitigate these effects. Approaches relying on matching single-slices, multipleslices and entire volumes in conjunction with different similarity measures suggested that using four slices at a time in combination with two sequential measures, Pearson correlation coefficient followed by mutual information, produced the best MRI-postmortem co-registration according to a voxel mismatch count. The accuracy of the overall registration was evaluated by measuring the 3D Euclidean distance between the locations of microscopically Identified lesions on post-mortem slices and their MRI-postmortem co-registered locations. The results show a mean 3D displacement of 5.1 ± 2.0 mm between the in vivo MRI and microscopically determined locations for 21 vascular lesions in 11 subjects.