title: The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T2* mapping at 7 T MRI.
abstract: Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls. Cortical T2* maps were sampled at various depths throughout the cortex and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive index (CI), calculated from a principal component analysis on the whole battery, was tested by a general linear model. Cognitive impairment correlated with T2* increase, independently from white matter lesions and cortical thickness, in cortical areas highly relevant for cognition belonging to the default-mode network (p < 0.05 corrected). Dysfunction in different cognitive functions correlated with longer T2* in selective cortical regions, most of which showed longer T2* relative to controls. For most tests, this association was strongest in deeper cortical layers. Executive dysfunction, however, was mainly related with pathology in juxtameningeal cortex. T2* explained up to 20% of the variance of the CI, independently of conventional imaging metrics (adjusted-R2: 52-67%, p < 5.10- 4). Location of pathology across the cortical width and mantle showed selective correlation with impairment in differing cognitive domains. These findings may guide studies at lower field strength designed to develop surrogate markers of cognitive impairment in MS.
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Céline
authors.initials: C
authors.lastname: Louapre
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Sindhuja T
authors.initials: ST
authors.lastname: Govindarajan
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Costanza
authors.initials: C
authors.lastname: Giannì
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Madigan
authors.affiliation: Virginia Mason Medical Center, Seattle, WA, USA.
authors.forename: A Scott
authors.initials: AS
authors.lastname: Nielsen
authors.affiliation: Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Sloane
authors.affiliation: University of California San Diego, Department of Neuroscience, San Diego, CA, USA.
authors.forename: Revere P
authors.initials: RP
authors.lastname: Kinkel
authors.affiliation: A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA; Harvard Medical School, Boston, MA, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mainero
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
keywords: 7 Tesla MRI; BVMT - DR, brief visuo-spatial memory test delayed recall; BVMT, brief visual memory test; CI, cognitive index; CVLT, California verbal learning test; Cognitive impairment; DB, digit span backward; DF, digit span forward; DR, delayed recall; EDSS, expanded disability status score; JLOT, judgment of line orientation test; LDCR, long delayed cued recall; LDFR, long delayed free recall; Laminar cortical pathology; MRI, magnetic resonance imaging; MS, multiple sclerosis; Multiple sclerosis; NP, neuropsychological; PCA, principal component analysis; SDMT, symbol digit modalities test; T2*; TMT, trail making test; TOT, total recall; WCST, Wisconsin card sorting test; WM, white matter; WMLV, white matter lesion volume; q-T2*, quantitative T2*