By providing excellent contrast of soft tissue, magnetic resonance imaging (MRI) has proven to be a useful diagnostic tool in medical imaging. MRI can provide excellent anatomical detail, yet it can also provide functional information about the tissue (e.g. blood flow, water diffusion, etc.). In order for the full potential of MRI to be realized, the influence of the physiological microstructure of tissue on the various tissue water parameters such as transverse relaxation, longitudinal relaxation, diffusion, and magnetization transfer must be understood. Our investigations focused on the diffusion of water and, to a lesser-extent, on the magnetization transfer between water protons (i.e. hydrogen nucleus) and macromolecular protons in excised nerves that were used as models of white matter.

Anisotropic water diffusion is observed in normal nerve and white matter. Myelin was hypothesized as the source of this anisotropy, but its role remained experimentally unproven. Therefore, the relative importance of the major structural components of nerve to anisotropic diffusion was evaluated by measuring water diffusion in various simplified models of white matter. The role of myelin was cast into doubt by the observation that nonmyelinated and myelinated nerves of the garfish had similar degrees of anisotropy. Further studies eliminated microtubules, fast axonal transport, neurofilaments, and local magnetic-susceptibility-induced gradients as primary sources of anisotropy. Hence, only membranes, either in the form (of myclin (if present) or axonal membranes, remained as the dominant source or anisotropic diffusion of axonral and inter-axonal water in nerve and presumably in white matter. We subsequently showed that anisotropy was significantly reduced in peripheral nerve that had undergone Wallerian degeneration, thus potentially providing a method of monitoring gross nerve degeneration.

White matter shows greater magnetization transfer than gray matter, presumably due to the abundance of myelin in white matter. To further investigate the contributions of myelin, several magnetization transfer properties of water in myclinated and nonmyclinated nerves of the garfish were compared. The degree of magnetization transfer at steady-state was similar for all of the nerves, implying that MT is quite nonspecific.