New methods to register multiple hemispheric slices of the postmortem brain to anatomically corresponding in-vivo MRI slices within a 3D volumetric MRI are presented. Gel-embedding and fiducial markers are used to reduce geometrical distortions in the postmortem brain volume. The registration algorithm relies on a recursive extraction of warped MRI slices from the reference MRI volume using a modified non-linear polynomial transformation until matching slices are found. Eight different voxel similarity measures are tested to get the best co-registration cost and the results show that combination of two different similarity measures shows the best performance. After validating the implementation and approach through simulation studies, the presented methods are applied to real data. The results demonstrate the feasibility and practicability of the presented co­registration methods, thus providing a means of MR signal analysis and histological examination of tissue lesions via co­registered images of postmortem brain slices and their corresponding MRI sections. With this approach, it is possible to investigate the pathology of a disease through both routinely acquired MRls and postmortem brain slices, thus improving the understanding of the pathological substrates and their progression.