Failure Of Early Lesion Repair In Multiple Sclerosis Lesions With Persistent Phase RIM (P4.006)

Objective. Characterizing early lesion evolution according to the pattern of contrast enhancement and phase rim may allow in vivo tracking of tissue remodeling/repair. Background. In some active demyelinating MS lesions, a strong immune reaction at the lesion edge is likely to contain lesion growth and isolate the lesion from surrounding unaffected parenchyma. Our previous studies (Gaitan et al., Ann Neurol 2011; Absinta et al., Ann Neurol 2013) suggest that this process involves secondary opening of the blood-brain barrier in capillaries at the lesion edge (seen as a centripetal pattern of contrast enhancement by MRI) and probable infiltration of M1 monocytes/microglia (seen as a phase rim due to paramagnetic substances such as iron). Methods. 19 centripetally and 18 centrifugally enhancing lesions were studied at 7 tesla MRI in 16 MS cases. High-resolution T2* gradient-echo scans, T1 scans before/after gadolinium, and dynamic contrast-enhanced T1 scans were acquired at baseline and months 1, 3, 6, 12. For each lesion, the time evolution of phase rim and lesion volume was assessed. Results. In all centripetal lesions, a phase rim colocalized with the initial site of contrast enhancement. In 10 of 19, the phase rim persisted after enhancement resolved; in the remaining 9, it disappeared. Compared to centripetal lesions with transient rim, those with persistent rim were larger at baseline and had less volume shrinkage between months 3 and 12 (p=0.01). Centrifugal lesions were smaller, and none developed a phase rim at any time point. Conclusion. The persistence of a phase rim in lesions that shrink least over time suggests that the rim marks the failure of early lesion repair. From a pathological point of view, we hypothesize that the rim corresponds to a high ratio of M1 (iron-laden) to M2 (anti-inflammatory) monocytes at the lesion edge, with consequent inhibition of oligodendrocyte differentiation/maturation and remyelination.