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

Assunta Dal-Bianco1, Günther Grabner2,3, Claudia Kronnerwetter3

  • 1Department of Neurology, Medical University of Vienna, Vienna, Austria.

Acta Neuropathologica
|November 1, 2016
PubMed

Insights

Iron accumulation in microglia/macrophages at multiple sclerosis (MS) lesion edges forms visible rims on 7 Tesla MRI. These rim lesions, indicating chronic activity, significantly expand over time compared to non-rim lesions.

Area of Science:

  • Neuroimmunology
  • Neuroimaging
  • Neuropathology

Background:

  • Iron accumulates in activated microglia/macrophages at chronic demyelinated lesion edges in multiple sclerosis (MS), forming signal-reducing rims on susceptibility-based 7 Tesla MRI.
  • These iron rims are associated with slowly expanding lesions, suggesting ongoing disease activity.

Purpose of the Study:

  • To investigate lesion types and stages associated with iron rims.
  • To identify the cells accumulating iron and their activation status.
  • To assess the reliability of 7 Tesla MRI in detecting iron rims.
  • To determine if MS lesions with rims enlarge over time in vivo.

Main Methods:

  • Histological analysis of iron, myelin, and microglia/macrophages in 28 MS brain sections.
  • Post-mortem 7 Tesla susceptibility-weighted imaging of 4 MS cases prior to histology.
  • Longitudinal in vivo 7 Tesla MRI and neurological examinations of 7 MS patients over 3.5 years.
  • Correlation of MRI findings with pathological iron rim presence and lesion expansion.

Main Results:

  • Iron rims were found around slowly expanding and some inactive lesions, but not remyelinated plaques.
  • Iron was primarily in pro-inflammatory microglia/macrophages, rarely in astrocytes.
  • Histology validated 7 Tesla MRI detection of iron rims, with slowly expanding lesions exceeding the iron-laden microglia threshold.
  • Rim lesions showed significant in vivo expansion over 3.5 years compared to non-rim lesions.

Conclusions:

  • Iron rims in MS lesions are associated with chronic inflammatory activity and are detectable by 7 Tesla MRI.
  • Lesions with iron rims exhibit significant in vivo expansion, serving as a potential MRI marker for MS disease activity.