Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis

Abstract

BackgroundQuantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([11C]PiB) can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS.MethodsPatients with active relapsing‐remitting MS (n = 20) and healthy controls (n = 8) were included in a longitudinal trial combining PET with [11C]PiB and magnetic resonance imaging. Voxel‐wise maps of [11C]PiB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination.ResultsAt baseline, there was a progressive reduction in [11C]PiB binding from the normal‐appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow‐up, high between‐patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p = 0.006 and beta‐coefficient = –0.67 with the Expanded Disability Status Scale; p = 0.003 and beta‐coefficient = –0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index.Interpretation[11C]PiB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. Ann Neurol 2016;79:726–738

Adaptive human immunity drives remyelination in a mouse model of demyelination

“…This theory was previously suggested by the observations in post-mortem tissue that a subset of multiple sclerosis patients exhibited more than 80% of their lesions remyelinated (Patrikios et al , 2006). Recently, the concept of good or bad ‘remyelinator’ was also supported by the dynamic imaging of remyelination patterns among multiple sclerosis patients (Bodini et al , 2016). …”

“…An endogenous myelin repair occurs in some patients (Bramow et al , 2010) but remyelination extent and efficacy is highly variable among patients and this variability is not linked to age, disease duration, or clinical forms of the disease (Patani et al , 2007). A recent longitudinal follow-up of newly formed demyelinated lesions—using PET and MRI combined with myelin specific markers—documented a large interindividual heterogeneity of remyelination (Bodini et al , 2016). Interestingly, the remyelination index was inversely correlated with clinical disability, a result confirming that myelin repair is essential to slower disease evolution.…”

Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward

“…This, however, may be largely a technical issue, as a diffusion tensor approach did show a spatial association between GM atrophy and adjoining diffuse WM damage (Bodini et al, 2009). The latter finding was later confirmed longitudinally (Bodini et al, 2016), and it was suggested that WM damage causes GM atrophy more so than the other way around. While this may certainly be true, second-order effects may start playing a role in later disease stages.…”

Imaging of microglial activation in MS using PET: Research use and potential future clinical application

“…PET studies on MS have focused on evaluating microglial activation using the 18 kDa translocator protein (TSPO) ligands, and on developing ways to assess remyelination. 5 In this topical review, we describe the advances made in imaging microglial activation in the field of MS, and discuss its challenges and future prospects.…”