Is the Relationship between Cortical and White Matter Pathologic Changes in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR Imaging Study with Surface and Tract-based Analysis.
OBJECTIVE
To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability.


METHODS
This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models.


RESULTS
In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P < .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P < .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (β = 4.6 × 10(3); P < .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (β = -4.3 × 10(4); P < .01), and T2* in the cingulum cortical projection at 25% depth (β = -1.7; P < .05).


CONCLUSIONS
Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism.
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Céline
C
Louapre
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Sindhuja T
ST
Govindarajan
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Costanza
C
Giannì
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Julien
J
Cohen-Adad
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Michael D
MD
Gregory
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
A Scott
AS
Nielsen
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Nancy
N
Madigan
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Jacob A
JA
Sloane
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Revere P
RP
Kinkel
From the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Building 149, Thirteenth St, Charlestown, MA 02129 (C.L., S.T.G., C.G., C.M.); Department of Radiology, Harvard Medical School, Boston, Mass (C.L., C.G., C.M.); Department of Electrical Engineering, École Polytechnique de Montréal, Montreal, QC, Canada (J.C.A.); Section on Integrative Neuroimaging, National Institute of Mental Health, National Institutes of Health, Bethesda, Md (M.D.G.); Department of Neurology and Neurosurgery, Virginia Mason Medical Center, Seattle, Wash (A.S.N.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass (N.M., J.A.S.); and Department of Neurosciences, University of California-San Diego, San Diego, Calif (R.P.K.).
Caterina
C
Mainero
D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009103:Multiple Sclerosis / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011446:Prospective Studies