Positron emission tomography with [ 18F]-DPA-714 unveils a smoldering component in most multiple sclerosis lesions driving disease progression

Positron emission tomography with18kDa-translocator (TSPO) tracers opens the perspective to image innate immune cells underlying the smoldering component of multiple sclerosis (MS), that currently mostly escape from MRI evaluation. Using [18F]-DPA-714-PET, we developed a novel lesion TSPO based classification of MS lesions and showed that an unexpectedly high proportion have a persistent neuroinflammatory content. A longitudinal follow up of subjects unraveled that this lesional smoldering component predicted atrophy and clinical progression. Following the acute phase, most lesions may therefore develop a chronic inflammatory component which can persist for several years, subsequently promoting neurodegeneration and clinical progression in MS.