Post mortem mapping of connectional anatomy for the validation of diffusion MRI

Despite the impressive advances in diffusion MRI (dMRI) acquisition and analysis that have taken place during the Human Connectome era, dMRI tractography is still an imperfect source of information on the circuitry of the brain. In this review, we discuss methods for post mortem validation of dMRI tractography, fiber orientations, and other microstructural properties of axon bundles that are typically extracted from dMRI data. These methods include anatomic tracer studies, Klinglers dissection, myelin stains, label-free optical imaging techniques, and others. We provide an overview of the basic principles of each technique, its limitations, and what it has taught us so far about the accuracy of different dMRI acquisition and analysis approaches.