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Cited by 245Advanced MRI Techniques and ApplicationsMultiple Sclerosis Research StudiesAdvanced Neuroimaging Techniques and Applications

Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron

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Wisnieff, Cynthia, Ramanan, Sriram, Olesik, John, Gauthier, Susan, Wang, Yi, Pitt, David·2015·Magnetic Resonance in Medicine
DOI 10.1002/mrm.25420PMC PMC4333139
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Abstract

Purpose: Within multiple sclerosis (MS) lesions iron is present in chronically activated microglia. Thus, iron detection with MRI might provide a biomarker for chronic inflammation within lesions. Here, we examine contributions of iron and myelin to magnetic susceptibility of lesions on quantitative susceptibility mapping (QSM). Methods: Fixed MS brain tissue was assessed with MRI including gradient echo data, which was processed to generate field (phase), R2* and QSM. Five lesions were sectioned and evaluated by immunohistochemistry for presence of myelin, iron and microglia/macrophages. Two of the lesions had an elemental analysis for iron concentration mapping, and their phospholipid content was estimated from the difference in the iron and QSM data. Results: Three of the five lesions had substantial iron deposition that was associated with microglia and positive susceptibility values. For the two lesions with elemental analysis, the QSM derived phospholipid content maps were consistent with myelin labeled histology. Conclusion: Positive susceptibility values with respect to water indicate the presence of iron in MS lesions, although both demyelination and iron deposition contribute to QSM. Magn Reson Med 74:564–570, 2015. © 2014 Wiley Periodicals, Inc.

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  • The data set of 48 data points suffices to fit the regression models and evaluate correlations.

    “Practically, this led to the construction of a data set of 48 data points, whose size suffices to fit the regression models and evaluate correlations (other high‐impact studies on MRI‐histopathology correlation relied on the same amount of data20 or even less17).”

    From Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology? (2017) · cites this paper as [17]

    The cited paper’s Methods and Results describe MRI–histopathology comparisons, but our copy does not report a dataset of 48 data points or establish that 48 suffice for regression and correlation analysis. The Discussion instead says that differing slice thicknesses make meaningful voxel-based linear regression difficult; it does not assess the sufficiency of a 48-point dataset (searched: 48 data points, regression, correlations). (LLM, conf=0.76)

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References 51 · Cited by 245

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Authors
Wisnieff, C., Ramanan, S., Olesik, J., Gauthier, S., Wang, Y., & Pitt, D.
Affiliations
  • Cornell University (US)
  • Yale University (US)
  • The Ohio State University (US)
  • Weill Cornell Medicine (US)
Corresponding author
Wang, Yi
ORCID
Venue
Magnetic Resonance in Medicine
Publisher
Wiley
Published
2014-08-18
Volume
74
Issue
2
Pages
564-570
ISSN
  • 0740-3194 (ISSN-L)
  • 1522-2594
DOI
10.1002/mrm.25420
PMC
PMC4333139
OpenAlex
W1848702082
Cited by
245
References
51
Citations by year
2026: 13 · 2025: 17 · 2024: 18 · 2023: 19 · 2022: 24 · 2021: 29 · 2020: 29 · 2019: 20 · 2018: 28 · 2017: 24 · 2016: 19 · 2015: 5
FWCI
12.49
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Magnetic Resonance in Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Multiple Sclerosis Society (RG4866-A-2)
  • NIH (R01NS072370, R01EB013443, S10RR025145)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
quantitative susceptibility mapping, multiple sclerosis lesions, iron accumulation, microglia, myelin, magnetic susceptibility, demyelination, chronic inflammation, phospholipid content, R2* mapping, iron status biomarkers
MeSH terms
Aged, Female, Humans, Image Enhancement, Image Interpretation, Computer-Assisted, Iron, Magnetic Resonance Imaging, Male, Multiple Sclerosis, Magnetic Resonance Spectroscopy, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Molecular Imaging, White Matter

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