Five-year longitudinal changes in quantitative spinal cord MRI in multiple sclerosis

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.

Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis

“…4 Nonetheless, due to recent methodologic improvements, a growing number of SC MR imaging studies in MS have been reported, mostly using DTI 5 and conventional magnetization transfer (MT) 6 imaging, highlighting SC microstructural changes with significant correlations to physical disability. 7,8 Although highly sensitive to MS-related tissue changes, both DTI and MT metrics are not specific to myelin damage because they could also be affected by inflammation and/or axonal loss. 9 Tremendous effort has thus recently been made toward the development of more myelin-specific MR imaging techniques.…”

Imaging of the Spinal Cord in Multiple Sclerosis: Past, Present, Future

“…The study introduced a new biomarker, the column-specific MTCSF, that not only correlates with sensorimotor disability but also explains their variance [ 48 ]. In a recent longitudinal study using a wide spectrum of quantitative SC MRI measures by Oh and colleagues, to assess disease progression over 5 years in RRMS and progressive MS, SC MTR at C3-4 level was the only measure significantly decreased at 2 and 5 years, followed by CSA that was significantly decreased only at 5 years MS [ 55 ]. The subject-specific longitudinal changes in cervical cord MTR correlated with disability measured by follow-up EDSS scores.…”

“…The subject-specific longitudinal changes in cervical cord MTR correlated with disability measured by follow-up EDSS scores. The study also reported strong correlations between the 2 year and 5 year subject-specific MTR changing rates suggesting that the 2-year course changes could be used to predict the long-term progression in MS [ 55 ].…”

“…Multi-compartment modeling of diffusion MRI, neurite orientation dispersion and density imaging (NODDI) and spherical mean technique (SMT), two other DTI analysis methods, are also of interest in imaging the SC [ 66 , 67 , 68 ]. These various diffusion imaging metrics have been broadly used in assessing the integrity and microstructure of the SC in MS [ 47 , 50 , 51 , 53 , 55 , 56 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Over the years, a number of different diffusion imaging models of the spinal cord have been used.…”

“…The study demonstrated that FA and MD histograms of the SC were significantly different in MS compared to controls, and correlated with clinical disability measures [ 47 ]. Oh et al employed DTI on a 3T MRI to assess disease progression in RRMS and progressive MS, but there were no significant changes captured at 2 and 5 years for all DTI metrics [ 55 ]. However, the subject-specific longitudinal changes on DTI indices were correlated with disability measured by EDSS.…”