title: High-resolution T1-relaxation time mapping displays subtle, clinically relevant, gray matter damage in long-standing multiple sclerosis.
abstract: Gray matter (GM) pathology has high clinical relevance in multiple sclerosis (MS), but conventional magnetic resonance imaging (MRI) is insufficiently sensitive to visualize the rather subtle damage.
  
  
  
  To investigate whether high spatial resolution T1-relaxation time (T1-RT) measurements can detect changes in the normal-appearing GM of patients with long-standing MS and whether these changes are associated with physical and cognitive impairment.
  
  
  
  High spatial resolution (1.05 × 1.05 × 1.2 mm(3)) T1-RT measurements were performed at 3 T in 156 long-standing MS patients and 54 healthy controls. T1-RT histogram parameters in several regions were analyzed to investigate group differences. Stepwise linear regression analyses were used to assess the relation of T1-RT with physical and cognitive impairment.
  
  
  
  In both thalamus and cortex, T1-RT histogram skewness was higher in patients than controls. In the cortex, this was driven by the frontal and temporal lobes. No differences were found in other GM histogram parameters. Cortical skewness, thalamus volume, and average white matter (WM) lesion T1-RT emerged as the strongest predictors for cognitive performance (adjusted R(2) = 0.39).
  
  
  
  Subtle GM damage was present in the cortex and thalamus of MS patients, as indicated by increased T1-RT skewness. Increased cortical skewness emerged as an independent predictor of cognitive dysfunction.
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Physics and Medical Technology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands m.steenwijk@vumc.nl.
authors.forename: Martijn D
authors.initials: MD
authors.lastname: Steenwijk
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Physics and Medical Technology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Jonkman
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marita
authors.initials: M
authors.lastname: Daams
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen Jg
authors.initials: JJ
authors.lastname: Geurts
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Physics and Medical Technology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Petra Jw
authors.initials: PJ
authors.lastname: Pouwels
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging* / Q000523:psychology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology / Q000523:psychology; D009929:Organ Size; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: MRI; Multiple sclerosis; cognition; disability; relaxometry; volumetry