Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI

Ferdinand Schweser, Jesper Hagemeier, Michael G. Dwyer, Niels Bergsland, Simon Hametner, Bianca Weinstock-Guttman, Robert Zivadinov

Research output: Contribution to journalArticlepeer-review


Increased brain iron concentration is often reported concurrently with disease development in multiple sclerosis (MS) and other neurodegenerative diseases. However, it is unclear whether the higher iron concentration in patients stems from an influx of iron into the tissue or a relative reduction in tissue compartments without much iron. By taking into account structural volume, we investigated tissue iron content in the deep gray matter (DGM) over 2 years, and compared findings to previously reported changes in iron concentration. 120 MS patients and 40 age- and sex-matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after 2 years. Overall, iron content was calculated from structural MRI and quantitative susceptibility mapping in the thalamus, caudate, putamen, and globus pallidus. MS patients had significantly lower iron content than controls in the thalamus, with progressive MS patients demonstrating lower iron content than relapsing–remitting patients. Over 2 years, iron content decreased in the DGM of patients with MS, while it tended to increase or remain stable among controls. In the thalamus, decreasing iron content over 2 years was associated with disability progression. Our study showed that temporally increasing magnetic susceptibility in MS should not be considered as evidence for iron influx because it may be explained, at least partially, by disease-related atrophy. Declining DGM iron content suggests that, contrary to the current understanding, iron is being removed from the DGM in patients with MS.

Original languageEnglish
JournalHuman Brain Mapping
Publication statusE-pub ahead of print - Dec 2020


  • iron content
  • longitudinal study
  • multiple sclerosis
  • QSM
  • quantitative susceptibility mapping

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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