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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 <jats:italic>content<\/jats:italic> in the deep gray matter (DGM) over 2\u2009years, and compared findings to previously reported changes in iron <jats:italic>concentration<\/jats:italic>. 120 MS patients and 40 age\u2010 and sex\u2010matched healthy controls were included. Clinical testing and MRI were performed both at baseline and after 2\u2009years. Overall, iron <jats:italic>content<\/jats:italic> 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\u2013remitting patients. Over 2\u2009years, iron content <jats:italic>decreased<\/jats:italic> 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\u2009years 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\u2010related atrophy. Declining DGM iron <jats:italic>content<\/jats:italic> suggests that, contrary to the current understanding, iron is being removed from the DGM in patients with MS.<\/jats:p>","DOI":"10.1002\/hbm.25306","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:05:23Z","timestamp":1609373123000},"page":"1463-1474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron <scp>MRI<\/scp>"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-9211","authenticated-orcid":false,"given":"Ferdinand","family":"Schweser","sequence":"first","affiliation":[{"name":"Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences University at Buffalo, The State University of New York  Buffalo New York 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