title: Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis.
abstract: OBJECTIVE
  To assess relationships between spinal cord MRI (SC-MRI) and retinal measures, and to evaluate whether these measures independently relate to clinical disability in multiple sclerosis (MS).
  
  
  METHODS
  One hundred two patients with MS and 11 healthy controls underwent 3-tesla brain and cervical SC-MRI, which included standard T1- and T2-based sequences and diffusion-tensor and magnetization-transfer imaging, and optical coherence tomography with automated segmentation. Clinical assessments included visual acuity (VA), Expanded Disability Status Scale, MS functional composite, vibration sensation threshold, and hip-flexion strength. Regions of interest circumscribing SC cross-sections at C3-4 were used to obtain cross-sectional area (CSA), fractional anisotropy (FA), perpendicular diffusivity (λ⊥), and magnetization transfer ratio. Multivariable regression assessed group differences and SC, retinal, and clinical relationships.
  
  
  RESULTS
  In MS, there were correlations between SC-CSA, SC-FA, SC-λ⊥, and peripapillary retinal nerve fiber layer (pRNFL) (p = 0.01, p = 0.002, p = 0.001, respectively) after adjusting for age, sex, prior optic neuritis, and brain atrophy. In multivariable clinical models, when SC-CSA, pRNFL, and brain atrophy were included simultaneously, SC-CSA and pRNFL retained independent relationships with low-contrast VA (p = 0.04, p = 0.002, respectively), high-contrast VA (p = 0.06, p = 0.008), and vibration sensation threshold (p = 0.01, p = 0.05). SC-CSA alone retained independent relationships with Expanded Disability Status Scale (p = 0.001), hip-flexion strength (p = 0.001), and MS functional composite (p = 0.004).
  
  
  CONCLUSIONS
  In this cross-sectional study of patients with MS, correlations exist between SC-MRI and retinal layers, and both exhibit independent relationships with clinical dysfunction. These findings suggest that the SC and optic nerve reflect ongoing global pathologic processes that supplement measures of whole-brain atrophy, highlighting the importance of combining measures from unique compartments to facilitate a thorough examination of regional and global disease processes that contribute to clinical disability in MS.
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD. pcalabr1@jhmi.edu joh20@jhu.edu.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Oh
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Elias S
authors.initials: ES
authors.lastname: Sotirchos
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Shiv
authors.initials: S
authors.lastname: Saidha
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Anna
authors.initials: A
authors.lastname: Whetstone
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Newsome
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Kathy
authors.initials: K
authors.lastname: Zackowski
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Elliot
authors.initials: E
authors.lastname: Frohman
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Jerry
authors.initials: J
authors.lastname: Prince
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Marie
authors.initials: M
authors.lastname: Diener-West
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
authors.affiliation: From the Departments of Neurology (J.O., E.S.S., S.S., A.W., S.D.N., K.Z., D.S.R., P.A.C.), Electrical and Computer Engineering (M.C., J.P.), Computer Science (J.P.), Physical Medicine and Rehabilitation (K.Z.), Biostatistics (M.C., M.D.-W., D.S.R.), and Radiology and Radiological Science (D.S.R.), Johns Hopkins University, Baltimore, MD; Division of Neurology (J.O.), Department of Medicine, St. Michael's Hospital, University of Toronto, Canada; Motion Analysis Laboratory (K.Z.), Kennedy Krieger Institute, Baltimore, MD; Department of Neurology (L.J.B.), University of Pennsylvania School of Medicine, Philadelphia; Departments of Neurology and Ophthalmology (E.F.), University of Texas Southwestern Medical Center at Dallas; and Translational Neuroradiology Unit (D.S.R.), National Institute of Neurological Disorders and Stroke, Bethesda, MD. pcalabr1@jhmi.edu joh20@jhu.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002574:Cervical Vertebrae; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D010363:Pattern Recognition, Automated; D012160:Retina / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*; D041623:Tomography, Optical Coherence