Quantitative myelin imaging with MRI and PET: an overview of techniques and their validation status.

Myelin is the protective sheath wrapped around axons, consisting of a phospholipid bilayer with water between the wraps. The measurement of damage to the myelin sheaths, the evaluation of the efficacy of therapies aiming to promote remyelination as well as monitoring the degree of brain maturation in children require non-invasive quantitative myelin imaging methods. To date, various myelin imaging techniques have been developed. Five different MRI approaches can be distinguished based on their biophysical principles: (1) imaging of the water between the lipid bilayers directly (e.g. myelin water imaging), (2) imaging the non-aqueous protons of the phospholipid bilayer directly with ultrashort echo time techniques, (3) indirect imaging of the macromolecular content (e.g. magnetization transfer; inhomogeneous magnetization transfer), (4) mapping of the effects of the myelin sheath's magnetic susceptibility on the MRI signal (e.g., quantitative susceptibility mapping), and (5) mapping of the effects of the myelin sheath on water diffusion. Myelin imaging with PET uses radioactive molecules with high affinity to specific myelin components, in particular myelin basic protein. This review aims to give an overview of the various myelin imaging techniques, their biophysical principles, image acquisition, data analysis, and their validation status.