Mechanisms of T2 anisotropy and gradient echo myelin water imaging

In MRI, structurally aligned molecular or micro‐organization (e.g. axonal fibers) can be a source of substantial signal variations that depend on the structural orientation and the applied magnetic field. This signal anisotropy gives us a unique opportunity to explore information that exists at a resolution several orders of magnitude smaller than that of typical MRI. In this review, one of the signal anisotropies, T2* anisotropy in white matter, and a related imaging method, gradient echo myelin water imaging (GRE‐MWI), are explored. The T2* anisotropy has been attributed to isotropic and anisotropic magnetic susceptibility of myelin and compartmentalized microstructure of white matter fibers (i.e. axonal, myelin, and extracellular space). The susceptibility and microstructure create magnetic frequency shifts that change with the relative orientation of the fiber and the main magnetic field, generating the T2* anisotropy. The resulting multi‐component magnitude decay and nonlinear phase evolution have been utilized for GRE‐MWI, assisting in resolving the signal fraction of the multiple compartments in white matter. The GRE‐MWI method has been further improved by signal compensation techniques including physiological noise compensation schemes. The T2* anisotropy and GRE‐MWI provide microstructural information on a voxel (e.g. fiber orientation and tissue composition), and may serve as sensitive biomarkers for microstructural changes in the brain. Copyright © 2016 John Wiley & Sons, Ltd. A white matter voxel demonstrates T2* anisotropy that originates from isotropic and anisotropic magnetic susceptibility and multi‐compartmental microstructure induced frequency shifts. These mechanisms result in multi‐exponential magnitude decay and nonlinear phase evolution. Using the complex signal, myelin water fraction can be estimated, producing gradient echo myelin water imaging.