title: Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.
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.
authors: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors: Assunta
authors: A
authors: Dal-Bianco
authors: Department of Health Sciences and Social Work, Carinthia University of Applied Sciences, Klagenfurt, Austria.|Department of Biomedical Imaging and Image-guided Therapy, High Field Magnetic Resonance Centre, Vienna, Austria.
authors: Günther
authors: G
authors: Grabner
authors: Department of Biomedical Imaging and Image-guided Therapy, High Field Magnetic Resonance Centre, Vienna, Austria.
authors: Claudia
authors: C
authors: Kronnerwetter
authors: Department of Biomedical Imaging and Image-guided Therapy, High Field Magnetic Resonance Centre, Vienna, Austria.
authors: Michael
authors: M
authors: Weber
authors: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors: Romana
authors: R
authors: Höftberger
authors: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Thomas
authors: T
authors: Berger
authors: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors: Eduard
authors: E
authors: Auff
authors: Department of Neurology, Medical University of Vienna, Vienna, Austria.
authors: Fritz
authors: F
authors: Leutmezer
authors: Department of Biomedical Imaging and Image-guided Therapy, High Field Magnetic Resonance Centre, Vienna, Austria.
authors: Siegfried
authors: S
authors: Trattnig
authors: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors: Hans
authors: H
authors: Lassmann
authors: Neuroimmunology Division/Neuroimaging Unit, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors: Francesca
authors: F
authors: Bagnato
authors: Center for Brain Research, Medical University of Vienna, Vienna, Austria. simon.hametner@meduniwien.ac.at.
authors: Simon
authors: 0000-0002-5160-5208
authors: S
authors: Hametner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D007501:Iron
keywords: 7 T MRI; Iron rim; Multiple sclerosis; Phase; SWI