Measuring Pathology in Patients with Multiple Sclerosis Using Positron Emission Tomography

Multiple sclerosis is characterized by a diverse and complex pathology. Clinical relapses, the hallmark of the disease, are accompanied by focal white matter lesions with intense inflammatory and demyelinating activity. Prevention of these relapses has been the major focus of pharmaceutical development, and it is now possible to dramatically reduce this inflammatory activity. Unfortunately, disability accumulation persists for many people living with multiple sclerosis owing to ongoing damage within existing lesions, pathology outside of discrete lesions, and other yet unknown factors. Understanding this complex pathological cascade will be critical to stopping progressive multiple sclerosis. Positron emission tomography uses biochemically specific radioligands to quantitatively measure pathological processes with molecular specificity. This review examines recent advances in the understanding of multiple sclerosis facilitated by positron emission tomography and identifies future avenues to expand understanding and treatment options.

An increasing number of radiotracers allow for the quantitative measurement of inflammatory abnormalities, de- and re-myelination, and metabolic disruption associated with multiple sclerosis. The studies have identified contributions of ongoing, smoldering inflammation to accumulating tissue injury and clinical worsening. Myelin studies have quantified the dynamics of myelin loss and recovery. Lastly, metabolic changes have been found to contribute to symptom worsening. The molecular specificity facilitated by positron emission tomography in people living with multiple sclerosis will critically inform efforts to modulate the pathology leading to progressive disability accumulation. Existing studies show the power of this approach applied to multiple sclerosis. This armamentarium of radioligands allows for new understanding of how the brain and spinal cord of people is impacted by multiple sclerosis.