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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10-27

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

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. More... »

PAGES

25-42

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00401-016-1636-z

DOI

http://dx.doi.org/10.1007/s00401-016-1636-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028461185

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27796537


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73 microglia/macrophages
74 multiple sclerosis
75 multiple sclerosis iron rim lesions
76 myelin
77 neurological examination
78 pathology
79 patients
80 plaques
81 post-mortem susceptibility-weighted imaging
82 pro-inflammatory activation status
83 quantitative thresholds
84 recovery/
85 resonance
86 resonance imaging
87 rim
88 rim lesions
89 sclerosis
90 sclerosis iron rim lesions
91 sections
92 sequence
93 shadow plaques
94 signals
95 slow expansion
96 stage
97 status
98 susceptibility-based magnetic resonance
99 susceptibility-weighted imaging
100 threshold
101 time
102 types
103 validation
104 vivo
105 years
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