Magnetization transfer imaging is used in multiple sclerosis because of its sensitivity to tissue destruction; in particular, to demyelination. This sensitivity was established in animal models and human diseases. Studies in experimental auto-immune encephalomyelitis have shown that the magnetization transfer ratio is slightly decreased in inflammatory lesions of the central nervous system white matter without demyelination but is more decreased in demyelinated lesions according to the level of myelin loss. Toxic demyelination studies and human studies in progressive multifocal leukoencephalopathy have confirmed that pure moderate to severe demyelination can be monitored by this technique. Axon loss can also contribute to the decrease of this ratio. Magnetization transfer is a validated technique to assess tissue destruction in central nervous system white matter diseases.