Jiwon Oh1, Min Chen2, Kateryna Cybulsky3, Suradech Suthiphosuwan4, Estelle Seyman3, Blake Dewey5, Marie Diener-West6, Peter van Zijl7, Jerry Prince8, Daniel S Reich9, Peter A Calabresi10. 1. Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada/Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. 2. Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA/Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA. 3. Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 4. Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada/Division of Neuroradiology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 5. Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA/F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. 6. Department of Biostatistics, Johns Hopkins University, Baltimore, MD, USA. 7. F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA/Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA. 8. Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA/Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA. 9. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA/Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA/Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. 10. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
Abstract
BACKGROUND: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). OBJECTIVES: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. METHODS: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3-C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. RESULTS: SC-CSA and MTR decreased (p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson's r with FA = -0.23 (p < 0.001); MD = 0.31 (p < 0.001); λ⊥ = 0.34 (p < 0.001); λ|| = -0.12 (p = 0.05), MTR = -0.37 (p < 0.001); SC-CSA = -0.47 (p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated (r = 0.93-0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). CONCLUSION: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.
BACKGROUND: The spinal cord (SC) is highly relevant to disability in multiple sclerosis (MS), but few studies have evaluated longitudinal changes in quantitative spinal cord magnetic resonance imaging (SC-MRI). OBJECTIVES: The aim of this study was to characterize the relationships between 5-year changes in SC-MRI with disability in MS. METHODS: In total, 75 MS patients underwent 3 T SC-MRI and clinical assessment (expanded disability status scale (EDSS) and MS functional composite (MSFC)) at baseline, 2 and 5 years. SC-cross-sectional area (CSA) and diffusion-tensor indices (fractional anisotropy (FA), mean, perpendicular, parallel diffusivity (MD, λ⊥, λ||) and magnetization transfer ratio (MTR)) were extracted at C3-C4. Mixed-effects regression incorporating subject-specific slopes assessed longitudinal change in SC-MRI measures. RESULTS:SC-CSA and MTR decreased (p = 0.009, p = 0.03) over 5.1 years. There were moderate correlations between 2- and 5-year subject-specific slopes of SC-MRI indices and follow-up EDSS scores (Pearson's r with FA = -0.23 (p < 0.001); MD = 0.31 (p < 0.001); λ⊥ = 0.34 (p < 0.001); λ|| = -0.12 (p = 0.05), MTR = -0.37 (p < 0.001); SC-CSA = -0.47 (p < 0.001) at 5 years); MSFC showed similar trends. The 2- and 5-year subject-specific slopes were robustly correlated (r = 0.93-0.97 for FA, λ⊥, SC-CSA and MTR, all ps < 0.001). CONCLUSION: In MS, certain quantitative SC-MRI indices change over 5 years, reflecting ongoing tissue changes. Subject-specific trajectories of SC-MRI index change at 2 and 5 years are strongly correlated and highly relevant to follow-up disability. These findings suggest that individual dynamics of change should be accounted for when interpreting longitudinal SC-MRI measures and that measuring short-term change is predictive of long-term clinical disability.
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