We are continuing to develop Diffusion Tensor MRI as both a clinical diagnostic tool and a basic research imaging modality. It consists of (a) statistically estimating an effective diffusion tensor of water, D, in a voxel from a series of diffusion-weighted images (DWIs), and (b) using D to obtain new information about tissue microstructure and physiology. Images of diffusion ellipsoids depict local fiber orientation and mean diffusion distances, while images of scalar invariants of D reveal microstructural information about tissues independent of the laboratory reference frame. Recently we proposed a family of new scalar invariants that behave like quantitative histological or physiological stains for diffusion isotropy, diffusion anisotropy, structural similarity, and degree of fiber-tract coherence. Drs. Pierpaoli and Jezzard have developed new ultrafast, interleaved, multislice, navigator-echo-corrected diffusion-weighted EPI sequences that permit Diffusion Tensor Imaging to be performed at sufficiently high resolution, quality, and speed for adequate radiological assessment in a clinical setting. Studies with normal human volunteers show that this new imaging modality can be used to segment brain tissue into white matter, gray matter, and CSF compartments. Moreover, diffusion anisotropy in white matter is found to be highly variable in human brain, and much larger than was reported previously. In chronic stroke patients, Diffusion Tensor MRI was found to be effective in identifying regions that exhibited Wallerian degeneration or gliosis. Models of brain development and organization are now being studied.