Cynthia Wisnieff1,2, Sriram Ramanan3, John Olesik4, Susan Gauthier5, Yi Wang1,2,6, David Pitt3. 1. Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA. 2. Department of Radiology, Weill Cornell Medical College, New York, New York, USA. 3. Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA. 4. School of Earth Sciences, Ohio State University, Columbus, Ohio, USA. 5. Department of Neurology, Weill Cornell Medical College, New York, New York, USA. 6. Department of Biomedical Engineering, Kyung Hee University, Seoul, South Korea.
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.
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.
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