In vivo molecular imaging of brain tissue pathology in presymptomatic multiple sclerosis

The presence of focal lesions suggestive of multiple sclerosis (MS) seen with magnetic resonance imaging (MRI) in asymptomatic individuals defines the radiologically isolated syndrome (RIS). Pathologically, tissue changes in RIS subjects recapitulate, although being less extensive and pronounced, those observed in definite MS, with an amount of innate immune cell activation, myelin loss, gliosis, metabolic modifications, and structural damage affecting the neuro-axonal compartment. Conventional MRI, however, is not able to capture these biological abnormalities at the cellular and molecular level. Positron emission tomography (PET) with specific radiolabeled compounds could fill this gap, identifying in vivo and with higher granularity the processes underling the abnormal MRI signals. This review presents data obtained with PET in RIS individuals and discusses the potential application of this technique in exploring the different pathophysiologic changes going on in the RIS brain, with technical considerations on radiotracers already tested in MS or newly developed. By breaking up the study of complex tissular changes into single biological phenomena, the use of PET in RIS could encourage early interventions to selectively target each one of them, with potential consequences on the clinical conversion to MS.