The use of MRI in the study of neurological disorders includes three major categories: Prognostic value and patient management, Trial outcome markers to detect response to treatment, and studies to gain insight into disease mechanisms. The utility of MRI techniques to these ends depend on the specificity of the technique for myelin, the specificity for overall positive responses, sensitivity to pathological changes and improvements, and multicenter and clinical feasibility.

Myelin is essential for normal neuronal function but the impact of demyelination depends on the other factors associated with the pathology including impact on oligodendrocytes, astrocytes, and immune response. Multiple Sclerosis is an autoimmune disorder where myelin is targeted and ongoing immune mediated attacks culminate in widespread CNS demyelination and neuronal injury and loss. The roles of immune mediated demyelination and other mechanisms of neurodegeneration are currently not well understood.

Measuring demyelination in MS has ranged from relatively non-specific observations of lesions on T1-weighted and T2-weighted MRI to current quantitative MRI techniques that attempt to improve specificity for myelin. The effective specificity of MRI techniques for myelin depends on other concurrent pathological changes that influence the MRI signals, and arise from edema, glial and astrocytic cellular injury and loss, and inflammatory cellular infiltrates.

The problem at hand is the assessment of demyelinating disorders and particularly imaging of myelin status with MRI. This information will benefit all investigators and clinicians interested in neurological imaging of myelin and neuroinflammation in neurological disorders. With this information participants will be able to plan studies of myelin including prognostic, clinical trial outcomes, and disease mechanisms. They will also have the foundation to further investigate and weigh the many options and scenarios for myelin imaging with MRI. We review MRI techniques that have been used in the past and are now at the forefront for measurement of myelin status in neurological disorders. Multiple Sclerosis is the prototype demyelinating neurological disorders and this topic has taken on renewed interested with the advent of promising remyelination and reparative therapies. Prognosis and study of disease mechanisms also drive the development of techniques aimed at in vivo measurement of myelin status. MRI approaches tend to have high sensitivity but poor specificity in the detection of demyelination and remyelination. Low specificity may not be a significant detriment to a prognostic factor but may be uninformative from the perspective of mechanistic studies. Furthermore, practical considerations of clinical and multi center feasibility also limit the current use of some techniques. In this presentation, the above concepts will frame the various techniques that are in current use for imaging demyelination in the brain including T1 and T2 relaxation times based modeling of myelin water pool, magnetization transfer (MT) ratio and quantitative MT, diffusion MRI models including DTI, NODDI, as well hybrid methods to estimate g-ratios, and recent ultra short echo time sequences to directly measure bound pools with echo times in the microseconds.