Traditional neuropathological examination provides information about neurological disease or injury of a patient at a high-resolution level. Correlating this type of post mortem diagnosis with in vivo image data of the same patient acquired by non-invasive tomographic scans greatly complements the interpretation of any disease or injury. We present the validation of a registration method for correlating macroscopic pathological images with MR images of the same patient. This also allows for 3-D mapping of the distribution of pathological changes throughout the brain. As the validation deals with datasets of widely differing sampling, we propose a method using smooth curvilinear anatomical features in the brain which allows interpolation between wide-spaced samples. Curvilinear features are common anatomically, and if selected carefully have the potential to allow determination of the accuracy of co-registration across large areas of a volume of interest.