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Open Access 01-01-2017 | Original Paper

Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging

Authors: Assunta Dal-Bianco, Günther Grabner, Claudia Kronnerwetter, Michael Weber, Romana Höftberger, Thomas Berger, Eduard Auff, Fritz Leutmezer, Siegfried Trattnig, Hans Lassmann, Francesca Bagnato, Simon Hametner

Published in: Acta Neuropathologica | Issue 1/2017

Abstract

In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.

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Title: Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging
Authors: Assunta Dal-Bianco
Günther Grabner
Claudia Kronnerwetter
Michael Weber
Romana Höftberger
Thomas Berger
Eduard Auff
Fritz Leutmezer
Siegfried Trattnig
Hans Lassmann
Francesca Bagnato
Simon Hametner
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1636-z

At a glance: The ONWARDS insulin icodec trials

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Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging

Abstract

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Abstract

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