The treatment of multiple sclerosis (MS) has been transformed by the successful development of immunotherapies that efficiently reduce disease activity. Nevertheless, the prevention of disability progression is therapeutically challenging, particularly during the progressive phase of the disease. The strategies to counteract neurodegeneration include neuroprotection by enhancing myelin regeneration and repair, nerve conduction restoration and metabolic support of the axon. Trials of potential neuroreparative agents are becoming more important in the spectrum of MS research. However, adequate imaging outcomes are required that are sensitive and specific to myelin, while also being reproducible and clinically meaningful. Unfortunately, the conventional MRI sequences have limited specificity for myelination. This course will evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetization transfer ratio (MTR), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we will consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome. Animal studies have provided targets for interventions to improve brain and spinal cord remyelination, paving the way for the translation of this research to humans.