Validation of diffusion tensor MRI in the central nervous system using light microscopy: Quantitative comparison of fiber properties

Diffusion tensor imaging (DTI) provides an indirect measure of tissue structure on a microscopic scale. To date, DTI is the only imaging method that provides such information in vivo, and has proven to be a valuable tool in both research and clinical settings. In this study, we investigated the relationship between white matter structure and diffusion parameters measured by DTI. We used micrographs from light microscopy of fixed, myelin-stained brain sections as a gold standard for direct comparison with data from DTI. Relationships between microscopic tissue properties observed with light microscopy (fiber orientation, density and coherence) and fiber properties observed by DTI (tensor orientation, diffusivities and fractional anisotropy) were investigated. Agreement between the major eigenvector of the tensor and myelinated fibers was excellent in voxels with high fiber coherence. In addition, increased fiber spread was strongly associated with increased radial diffusivity (p=6×10 ^-6) and decreased fractional anisotropy (p=5×10 ^-8), and was weakly associated with decreased axial diffusivity (p=0.07). Increased fiber density was associated with increased fractional anisotropy (p=0.03), and weakly associated with decreased radial diffusivity (p<0.06), but not with axial diffusivity (p=0.97). The mean diffusivity was largely independent of fiber spread (p=0.24) and fiber density (p=0.34).