Background: 1 Neuropathological Advances in Multiple Sclerosis.- 2 Neurophysiology.- MRI Techniques to Assess Neurodegeneration: 3 Atrophy.- 4 T1 Black Holes and Gray Matter Damage.- 5 Magnetization Transfer Imaging.- 6 Perfusion MRI.- 7 Diffusion-Weighted Imaging.- 8 Proton MR Spectroscopy.- 9 Functional MRI.-Evaluation of MRI Outcomes: 10 Validation of MRI Surrogates.- 11 Defining Responders and Non-responders.-12 Predictive Models in Multimodal Imaging.- Lessons from other Neurodegenerative Diseases: 13 Alzheimer\'s Disease.- 14 Other Neurodegenerative Conditions.- 15 Incorporation of Other Biomarkers.- Designing MS Trials for Neurodegeneration.- 16 Critical Review of Existing Trials.- 17 Design for the Next Trials of Neurodegeneration.- Subject Index