Introduction Although conventional magnetic resonance imaging (MRI) can detect multiple sclerosis (MS) lesions with high sensitivity, it is not without relevant limitations. First, MRI is not specific with regard to the heterogeneous pathological substrates of individual lesions, which include edema, inflammation, demyelination, remyelination, gliosis, and axonal loss. Second, MRI does not delineate tissue damage occurring in the gray matter (GM) and in the normal-appearing white matter (NAWM), which is known to be damaged in these patients. These limitations are to some degree overcome by the use of gadolinium-enhancing (Gd-enhancing) T1-weighted images, which distinguish active from inactive lesions, since enhancement occurs as a result of increased blood–brain barrier (BBB) permeability and corresponds to areas with ongoing inflammation. However, the activity of the lesions as demonstrated on post-contrast T1-weighted imaging still provides only limited information on tissue damage. Chronically hypointense areas on T1-weighted images correspond to areas where severe tissue disruption has occurred, and their extent is correlated with the clinical severity of the disease and its evolution over time. Still, the extent of T1-hypointense lesions does not correspond to the severity of intrinsic lesion pathology and provides no information about NAWM and GM damage. Finally, the definition of hypointense is by nature highly subjective. A number of non-conventional MRI techniques have been developed and applied in efforts to improve understanding of the evolution of MS. These techniques, including magnetization transfer (MT) MRI, are designed to provide quantitative information with regard to MS microscopic and macroscopic lesion burdens with a higher pathological specificity to the most destructive aspects of MS than conventional MRI.
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