In multiple sclerosis (MS), conventional magnetic resonance imaging (cMRI) has proved to be a valuable tool to increase diagnostic confidence and for monitoring the efficacy of experimental treatment. However, cMRI has limited specificity and accuracy of cMRI to the most disabling aspects of the MS pathology, known to occur in and outside macroscopic lesions. Modern quantitative MR techniques have the potential to overcome the limitations of cMRI, and their application is changing dramatically our understanding of how MS causes irreversible disability. In detail, there is an increasing body of MR evidence that MS is not only a white matter disease and does not only cause focal lesions, as well as that neurodegeneration is an important aspect of the disease (since the earliest clinical phases), which is only partially related to inflammatory changes. There is also increasing perception that modern MR methodologies should be more extensively employed in clinical trials to derive innovative information. Written by world-renowned scientists, the volume provides a state-of-the-art on the most recent MRI techniques related to MS, and it will bi and indispensable tool for all those working in this field. TOC: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 In multiple sclerosis (MS), conventional magnetic resonance imaging (cMRI) has proved to be a valuable tool to increase diagnostic confidence and for monitoring the efficacy of experimental treatment. However, cMRI has limited specificity and accuracy of cMRI to the most disabling aspects of the MS pathology, known to occur in and outside macroscopic lesions. Modern quantitative MR techniques have the potential to overcome the limitations of cMRI, and their application is changing dramatically our understanding of how MS causes irreversible disability. In detail, there is an increasing body of MR evidence that MS is not only a white matter disease and does not only cause focal lesions, as well as that neurodegeneration is an important aspect of the disease (since the earliest clinical phases), which is only partially related to inflammatory changes. There is also increasing perception that modern MR methodologies should be more extensively employed in clinical trials to derive innovative information. Written by world-renowned scientists, the volume provides a state-of-the-art on the most recent MRI techniques related to MS, and it will bi and indispensable tool for all those working in this field. Background Neuropathological Advances in Multiple Sclerosis 3(8) E. Capello A. Uccelli M. Pizzorno G.L. Mancardi Neurophysiology 11(12) L. Leocani G. Comi MRI Techniques to Assess Neurodegeneration Atrophy 23(14) W. Rashid D.T. Chard D.H. Miller T1 Black Holes and Gray Matter Damage 37(10) M. Neema V.S.R. Dandamudi A. Arora J. Stankiewicz R. Bakshi Magnetization Transfer Imaging 47(8) M. Inglese Y. Ge R.I. Grossman Perfusion MRI 55(10) Y. Ge M. Law M. Inglese R.I. Grossman Diffusion-Weighted Imaging 65(10) M. Rovaris E. Perego M. Filippi Proton MR Spectroscopy 75(10) N. De Stefano Functional MRI 85(22) MA. Rocca M. Filippi Evaluation of MRI Outcomes Validation of MRI Surrogates 107(6) M.P. Sormani M. Filippi Defining Responders and Non-responders 113(14) I. Aban G. Cutter Predictive Models in Multimodal Imaging 127(26) K. Mouridsen L. 0stergaard Lessons from Other Neurodegenerative Diseases Alzheimer's Disease 153(10) G.B. Frisoni Other Neurodegenerative Conditions 163(20) M. Mascalchi Incorporation of Other Biomarkers 183(28) S. Gnanapavan G. Giovannoni Designing MS Trials for Neurodegeneration Critical Review of Existing Trials 211(10) G. Comi Design for the Next Trials of Neurodegeneration 221(12) P. Soelberg Sorensen Subject Index 233