Figure 5.

The “diffusion regimes.” (A) White matter is a complex—but relatively ordered— microstructure primarily composed of nerve fibers (axons) and glial cells. Axons are bundled together; their main role is to transport substances intra-cellularly through microtubules and conduct electricity to enable inter-communication between cells. The myelin sheath—a “fatty” insulating layer around the axons—facilitates such conduction. In the healthy brain, such microstructure exerts restrictive boundary conditions to water diffusion. (B) The exact mechanism by which microstructural damage occurs in neurodegenerative diseases is unknown but it is conceivable that, after a period of instability, demyelinative and other axon degeneration processes will lead to longer “diffusion paths.” If therefore, the diffusion time is sufficiently long and the gradients sufficiently strong, such diffusion behavior will yield a change in signal attenuation that will be reflected in tensor diffusivities. (C) If, however, some diffusing molecules cease to interact with microstructural barriers during a given diffusion time, the axial to radial relationship would be dependent on the local geometry leading to heterogeneous tensor behaviors across the brain. (D) In the extreme case, where the diffusion time is too short for molecular displacements to be hindered, tensor diffusivity measures would be unable to detect further change. Large b-values—enabling long diffusion times and strong gradients—make the diffusion measurement with magnetic resonance both more sensitive to subtle microstructural alterations in highly restricted environments, and less prone to diffusion-time dependencies.