Histological Validation of Diffusion MRI

Abstract

The ability of diffusion magnetic resonance imaging (dMRI) fiber tractography to non-invasively map the three-dimensional (3D) network of the human brain has proven to be a valuable neuroimaging tool, improving our understanding of both normal development and complex brain disorders. However, the process from data acquisition to generation of a 3D map of reconstructed fibers is a multi-step procedure with numerous assumptions and uncertainties that can ultimately affect the ability of this technique to faithfully represent the true axonal connections of the brain. Because of this, validating dMRI tractography is required on many levels. It is necessary not only to measure the ability of these techniques to track white matter fibers from voxel to voxel, but also to quantify the ability of dMRI to assess the underlying fiber orientation distribution (FOD) within each voxel. To do this, we propose to compare diffusion data directly to histology data on both the microstructural scale of tissues and the macrostructural scale of brain connectivity. These experiments will lead to a better understanding of the limitations and pitfalls of dMRI experiments, and provide a quantitative assessment of the reliability of these techniques.