title: A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging.
abstract: We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤ 3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥ 4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients' normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10(-10) and P < 10(-7)), and mean cortical T2* in controls (P < 10(-5) and P < 10(-6)). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface.
authors: 1 A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA caterina@nmr.mgh.harvard.edu.
authors: Caterina
authors: C
authors: Mainero
authors: 1 A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA.
authors: Céline
authors: C
authors: Louapre
authors: 1 A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA.
authors: Sindhuja T
authors: ST
authors: Govindarajan
authors: 1 A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA.
authors: Costanza
authors: C
authors: Giannì
authors: 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA 3 Beth Israel Deaconess Medical Center, Boston, MA, USA 4 Virginia Mason Medical Center, Seattle, WA, USA.
authors: A Scott
authors: AS
authors: Nielsen
authors: 1 A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA 5 Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.
authors: Julien
authors: J
authors: Cohen-Adad
authors: 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA 3 Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors: Jacob
authors: J
authors: Sloane
authors: 2 Harvard Medical School, 25 Shattuck Street, Boston, MA 02115,USA 3 Beth Israel Deaconess Medical Center, Boston, MA, USA 6 University of California San Diego, USA.
authors: Revere P
authors: RP
authors: Kinkel
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000378:metabolism*; D011446:Prospective Studies
keywords: 7 T MRI; gyri; multiple sclerosis; quantitative T2*; subpial demyelination; sulci