title: Cortical Perfusion Alteration in Normal-Appearing Gray Matter Is Most Sensitive to Disease Progression in Relapsing-Remitting Multiple Sclerosis.
abstract: The role of gray matter in multiple sclerosis is increasingly evident; however, conventional images demonstrate limitations in cortical lesion identification. Perfusion imaging appears sensitive to changes in tissue type and disease severity in MS. We sought to use bookend perfusion to quantify parameters in healthy controls and normal-appearing and lesional tissue at different relapsing-remitting MS stages.
  
  
  
  Thirty-nine patients with relapsing-remitting MS and 19 age-matched healthy controls were prospectively recruited. The Minimal Assessment of Cognitive Function in MS battery was used to assess cognitive performance. Perfusion parameters, including cerebral blood flow and volume and mean transit time, were compared for healthy controls and normal-appearing and lesional tissue for all study groups. Dispersion of perfusion measures for white matter lesions and cortical lesions was assessed.
  
  
  
  Twenty of the 39 patients with relapsing-remitting MS were cognitively impaired. Significant differences were displayed between all relapsing-remitting MS subgroups and healthy controls in all comparisons except for normal-appearing gray matter CBV between healthy controls and unimpaired patients with relapsing-remitting MS and for all normal-appearing white matter perfusion parameters between healthy controls and unimpaired patients with relapsing-remitting MS. White matter lesion but not cortical lesion perfusion was significantly reduced in cognitively impaired patients with relapsing-remitting MS versus unimpaired patients with relapsing-remitting MS. Perfusion reduction with disease progression was greater in normal-appearing gray matter and normal-appearing white matter compared with cortical lesions and white matter lesions. Smaller dispersion was observed for cortical lesions compared with white matter lesions for each perfusion parameter.
  
  
  
  Quantitative GM and WM analysis demonstrated significant but disproportionate white matter lesion, cortical lesion, normal-appearing white matter, and normal-appearing gray matter changes present between healthy controls and patients with relapsing-remitting MS with and without cognitive impairment, necessitating absolute rather than relative lesion perfusion measurement.
authors.affiliation: Medical Imaging (S.-P.H., M.K., R.V., R.I.A., L.Z.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Medical Imaging (S.-P.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada Parsa.Hojjat@sunnybrook.ca.
authors.forename: S-P
authors.identifier: 0000-0003-0188-1578
authors.initials: SP
authors.lastname: Hojjat
authors.affiliation: Medical Imaging (S.-P.H., M.K., R.V., R.I.A., L.Z.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: M
authors.identifier: 0000-0002-2044-5440
authors.initials: M
authors.lastname: Kincal
authors.affiliation: Medical Imaging (S.-P.H., M.K., R.V., R.I.A., L.Z.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: R
authors.identifier: 0000-0001-6416-6278
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: Departments of Biomedical Engineering (C.G.C., T.J.C.).
authors.forename: C G
authors.identifier: 0000-0003-0559-8681
authors.initials: CG
authors.lastname: Cantrell
authors.affiliation: From the Departments of Psychiatry (A.F.) Psychiatry (A.F.).
authors.forename: A
authors.identifier: 0000-0002-0132-0909
authors.initials: A
authors.lastname: Feinstein
authors.affiliation: Medical Imaging (S.-P.H., M.K., R.V., R.I.A., L.Z.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: L
authors.identifier: 0000-0002-5882-6070
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Neurology (L.L.) Departments of Medicine (P.O., L.L.).
authors.forename: L
authors.identifier: 0000-0001-7322-9672
authors.initials: L
authors.lastname: Lee
authors.affiliation: Departments of Medicine (P.O., L.L.).
authors.forename: P
authors.identifier: 0000-0002-5632-8385
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Departments of Biomedical Engineering (C.G.C., T.J.C.) Radiology (T.J.C.), Northwestern University, Chicago, Illinois.
authors.forename: T J
authors.identifier: 0000-0002-5149-8377
authors.initials: TJ
authors.lastname: Carroll
authors.affiliation: Medical Imaging (S.-P.H., M.K., R.V., R.I.A., L.Z.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Medical Imaging (S.-P.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada.
authors.forename: R I
authors.identifier: 0000-0003-0259-970X
authors.initials: RI
authors.lastname: Aviv
mesh_terms: D000328:Adult; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D055420:Perfusion Imaging / Q000379:methods*; D066127:White Matter / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult