Introduction

In inflammatory and demyelinating disorders of the central nervous system (CNS), conventional MR imaging (MRI) findings are unable to differentiate the heterogeneous pathological substrates of individual lesions, since different tissue changes (i.e., inflammation, demyelination, remyelination, gliosis, and axonal loss) lead to a similar appearance of increased signal intensity on T2-weighted images. Moreover, conventional MRI does not delineate tissue damage occurring beyond T2-visible lesions (i.e., in the normal-appearing white matter [NAWM] and gray matter [GM]).[1,2] Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) have the potential to improve our understanding of the pathophysiology of inflammatory and demyelinating disorders of the CNS, by overcoming some of these limitations.

Diffusion is the microscopic random translational motion of molecules in a fluid system. In the CNS, diffusion is influenced by the microstructural components of tissue, including cell membranes and organelles. The diffusion coefficient in biological tissues (which can be measured in vivo by DWI) is, therefore, lower than the diffusion coefficient in free water, and for this reason is named the apparent diffusion coefficient (ADC).[3] Pathological processes such as inflammatory-demyelination can modify tissue integrity, resulting in a loss (or increased permeability of) “restricting” barriers, and can, thus, result in an increase of the ADC. The measurement of diffusion is also dependent on the direction in which diffusion is measured, since within the time scale of the diffusion experiment water may diffuse unevenly in different directions, depending on the size and shape of the cellular structures. As a consequence, diffusion measurements can give information about the shape, integrity, and orientation of tissues,[4] which can also be altered by pathology. A full characterization of diffusion can be obtained in terms of a tensor,[5] a 3 × 3 matrix that accounts for the correlation existing between molecular displacement along orthogonal directions. From the tensor, it is possible to derive mean diffusivity (MD), a measure of diffusion that is independent of the orientation of structures (since it results from an average of the ADCs measured in three orthogonal directions, and it is equal to the one-third of its trace), and some other dimensionless indexes of anisotropy. One of the most used of these indices is the fractional anisotropy (FA).[6,7] Full details can be found in Chs. 4 and 5.