In vivo imaging of chronic active lesions in multiple sclerosis

Alberto Calvi, Lukas Haider, Ferran Prados, Carmen Tur, Declan Chard, Frederik Barkhof, Alberto Calvi, Lukas Haider, Ferran Prados, Carmen Tur, Declan Chard, Frederik Barkhof

Abstract

New clinical activity in multiple sclerosis (MS) is often accompanied by acute inflammation which subsides. However, there is growing evidence that a substantial proportion of lesions remain active well beyond the acute phase. Chronic active lesions are most frequently found in progressive MS and are characterised by a border of inflammation associated with iron-enriched cells, leading to ongoing tissue injury. Identifying imaging markers for chronic active lesions in vivo are thus a major research goal. We reviewed the literature on imaging of chronic active lesion in MS, focussing on 'slowly expanding lesions' (SELs), detected by volumetric longitudinal magnetic resonance imaging (MRI) and 'rim-positive' lesions, identified by susceptibility iron-sensitive MRI. Both SELs and rim-positive lesions have been found to be prognostically relevant to future disability. Little is known about the co-occurrence of rims around SELs and their inter-relationship with other emerging techniques such as dynamic contrast enhancement (DCE) and positron emission tomography (PET).

Keywords: Multiple sclerosis; chronic active lesions; imaging; magnetic resonance imaging; positron emission tomography.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.P. received a non-clinical Guarantors of the Brain fellowship. C.T. has received an ECTRIMS Post-doctoral Research Fellowship in 2015. She has also received honoraria and support from travelling from Merck Serono, Sanofi, Roche, TEVA Pharmaceuticals, Novartis, Biogen, Bayer and Ismar Healthcare. D.C. is a consultant for Biogen and Hoffmann-La Roche. In the last 2 years, he has received research funding from the International Progressive MS Alliance, the MS Society and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre. F.B. serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology and serves as a consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck.

Figures

Figure 1.
Figure 1.
Chronic active lesion pathology-imaging features: Panel (a) shows a cartoon of the iron deposition at the edge of a chronic active lesion and panel (b) shows an example of a hypointense rim on a susceptibility-weighted scan probably reflecting iron. Panel (c) shows a cartoon of activated microglia/macrophages in the periphery of a chronic active lesion and we assume that this inflammatory activity is responsible for low expansion of SEL lesion visible in (d).

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