title: Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity.
abstract: Susceptibility MR imaging contrast variations reflect alterations in brain iron and myelin content, making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study, we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes.
  
  
  
  Twenty-four subjects with multiple sclerosis underwent 7T MR imaging of the brain, disability examinations, and a fatigue inventory. The inverse of T2* relaxation time (R2*), frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions.
  
  
  
  Most lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than in progressive multiple sclerosis (54% versus 35%, P = .018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and patients with higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower in lesions in progressive multiple sclerosis (median, -0.018 ppm; range, -0.070 to 0.022) than in relapsing-remitting MS (median, -0.010 ppm; range, -0.062 to 0.052; P = .003).
  
  
  
  A progressive clinical phenotype and greater disability and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MR imaging may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation.
authors.affiliation: From the Department of Neurology (D.M.H.), University of Maryland School of Medicine, Baltimore, Maryland Departments of Neurology (D.M.H., P.A.C.) dharrison@som.umaryland.edu.
authors.forename: D M
authors.identifier: 0000-0001-8707-2004
authors.initials: DM
authors.lastname: Harrison
authors.affiliation: Radiology and Radiological Science (X.L., C.K.J., P.v.Z.) F.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: X
authors.identifier: 0000-0002-4350-3375
authors.initials: X
authors.lastname: Li
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland Department of Radiology (H.L.), Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, China.
authors.forename: H
authors.identifier: 0000-0001-7923-1925
authors.initials: H
authors.lastname: Liu
authors.affiliation: Radiology and Radiological Science (X.L., C.K.J., P.v.Z.) F.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: C K
authors.identifier: 0000-0002-0629-3006
authors.initials: CK
authors.lastname: Jones
authors.affiliation: Biostatistics (B.C.), Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: B
authors.identifier: 0000-0002-0793-9497
authors.initials: B
authors.lastname: Caffo
authors.affiliation: Departments of Neurology (D.M.H., P.A.C.).
authors.forename: P A
authors.identifier: 0000-0002-7776-6472
authors.initials: PA
authors.lastname: Calabresi
authors.affiliation: Radiology and Radiological Science (X.L., C.K.J., P.v.Z.) F.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland.
authors.forename: P
authors.identifier: 0000-0002-9706-1066
authors.initials: P
authors.lastname: van Zijl
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology*; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology