title: Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Positive susceptibility values with respect to water indicate the presence of iron in MS lesions, although both demyelination and iron deposition contribute to QSM.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.|Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Wisnieff
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Ramanan
authors.affiliation: School of Earth Sciences, Ohio State University, Columbus, Ohio, USA.
authors.forename: John
authors.initials: J
authors.lastname: Olesik
authors.affiliation: Department of Neurology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.|Department of Radiology, Weill Cornell Medical College, New York, New York, USA.|Department of Biomedical Engineering, Kyung Hee University, Seoul, South Korea.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pitt
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D007501:Iron
keywords: LA-ICP-MS iron quantification; MRI; MS lesion; QSM; quantitative susceptibility mapping