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 (l t ), 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-l t , and peripapillary retinal nerve fiber layer (pRNFL) (p 5 0.01, p 5 0.002, p 5 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 5 0.04, p 5 0.002, respectively), high-contrast VA (p 5 0.06, p 5 0.008), and vibration sensation threshold (p 5 0.01, p 5 0.05). SC-CSA alone retained independent relationships with Expanded Disability Status Scale (p 5 0.001), hip-flexion strength (p 5 0.001), and MS functional composite (p 5 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. Neurology ® 2015;84:720-728 GLOSSARY BPF 5 brain parenchymal fraction; CSA 5 cross-sectional area; DTI 5 diffusion tensor imaging; DW 5 diffusion weighted; EDSS 5 Expanded Disability Status Scale; FA 5 fractional anisotropy; FOV 5 field of view; GCL 5 ganglion cell layer; HC 5 healthy control; IPL 5 inner plexiform layer; lt 5 perpendicular diffusivity; MLR 5 multivariable linear regression; mRNFL 5 macular retinal nerve fiber layer; MS 5 multiple sclerosis; MSFC 5 multiple sclerosis functional composite; MT 5 magnetization transfer; MTR 5 magnetization transfer ratio; OCT 5 optical coherence tomography; PPMS 5 primary progressive multiple sclerosis; pRNFL 5 peripapillary retinal nerve fiber layer; RNFL 5 retinal nerve fiber layer; ROI 5 region of interest; RSEE 5 robust standard error estimation; SC 5 spinal cord; SPMS 5 secondary progressive mu...

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis

“…Whether these patterns are generally common to MS patients will need confirmation in larger and different MS patient cohorts. These data are also consistent with recent reports of correlations between spinal cord MRI measurement and retinal layers in MS, and associations between deep gray matter tissue damage and degeneration in cortex and spinal cord …”

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis

“…Whether these patterns are generally common to MS patients will need confirmation in larger and different MS patient cohorts. These data are also consistent with recent reports of correlations between spinal cord MRI measurement and retinal layers in MS, and associations between deep gray matter tissue damage and degeneration in cortex and spinal cord …”

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

“…In confirmation with previous studies, we found disability is heavily age-dependent [22, 23]. Related to gender [24‒27] or disease duration [24, 25, 27, 28], there are different articles that support our results, concluding no correlation with EDSS. Similarly, there are publications that do not support DMT patients’ history inclusion in an EDSS model [24, 26, 27].…”

“…Finally, our results are further corroborated by recent study [24] that assesses SC-OCT correlations. A multivariable model for the EDSS ( R 2 = 0.4) in a mixed cohort revealed that SC area and age were the only examined variables that correlated with EDSS.…”

“…Our results found that above 4.0 the EDSS is not only weighted toward the integrity of the pyramidal tract and the age of the patient, but also, although minimally, it is conditioned by GCL integrity. Finally, our outcomes suggest MS disability is better captured by SC and retinal parameters than brain atrophy, supporting the idea of pathological mechanisms at SC and retina distinct from the brain or at least, less clinically "silent" tissue injury at SC or retina than whole brain [24].…”

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability

“…In this study, the overall MTR coefficient of variation (aggregating between‐session, between‐scanner, and between‐participant variabilities) for the centered spinal cord levels C4‐C6 was about 3% (in our case, 1 pu). This value is similar to that reported in previous single‐scanner spinal cord studies (range: 1–2 pu, summarized in Supplementary Table 1), and even slightly smaller . Our result suggests that MTR values obtained using scanners from the same manufacturer with the same acquisition parameters can be used in multicenter studies without any drastic increase in the variability of the MTR measurements, relative to single‐center studies.…”

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis

“…Whether these patterns are generally common to MS patients will need confirmation in larger and different MS patient cohorts. These data are also consistent with recent reports of correlations between spinal cord MRI measurement and retinal layers in MS, and associations between deep gray matter tissue damage and degeneration in cortex and spinal cord …”

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

“…In confirmation with previous studies, we found disability is heavily age-dependent [22, 23]. Related to gender [24‒27] or disease duration [24, 25, 27, 28], there are different articles that support our results, concluding no correlation with EDSS. Similarly, there are publications that do not support DMT patients’ history inclusion in an EDSS model [24, 26, 27].…”

“…Finally, our results are further corroborated by recent study [24] that assesses SC-OCT correlations. A multivariable model for the EDSS ( R 2 = 0.4) in a mixed cohort revealed that SC area and age were the only examined variables that correlated with EDSS.…”

“…Our results found that above 4.0 the EDSS is not only weighted toward the integrity of the pyramidal tract and the age of the patient, but also, although minimally, it is conditioned by GCL integrity. Finally, our outcomes suggest MS disability is better captured by SC and retinal parameters than brain atrophy, supporting the idea of pathological mechanisms at SC and retina distinct from the brain or at least, less clinically "silent" tissue injury at SC or retina than whole brain [24].…”

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability

“…In this study, the overall MTR coefficient of variation (aggregating between‐session, between‐scanner, and between‐participant variabilities) for the centered spinal cord levels C4‐C6 was about 3% (in our case, 1 pu). This value is similar to that reported in previous single‐scanner spinal cord studies (range: 1–2 pu, summarized in Supplementary Table 1), and even slightly smaller . Our result suggests that MTR values obtained using scanners from the same manufacturer with the same acquisition parameters can be used in multicenter studies without any drastic increase in the variability of the MTR measurements, relative to single‐center studies.…”

Single scan quantitative gradient recalled echo MRI for evaluation of tissue damage in lesions and normal appearing gray and white matter in multiple sclerosis

“…Whether these patterns are generally common to MS patients will need confirmation in larger and different MS patient cohorts. These data are also consistent with recent reports of correlations between spinal cord MRI measurement and retinal layers in MS, and associations between deep gray matter tissue damage and degeneration in cortex and spinal cord …”

Design and Validation of an Expanded Disability Status Scale Model in Multiple Sclerosis

“…In confirmation with previous studies, we found disability is heavily age-dependent [22, 23]. Related to gender [24‒27] or disease duration [24, 25, 27, 28], there are different articles that support our results, concluding no correlation with EDSS. Similarly, there are publications that do not support DMT patients’ history inclusion in an EDSS model [24, 26, 27].…”

“…Finally, our results are further corroborated by recent study [24] that assesses SC-OCT correlations. A multivariable model for the EDSS ( R 2 = 0.4) in a mixed cohort revealed that SC area and age were the only examined variables that correlated with EDSS.…”

“…Our results found that above 4.0 the EDSS is not only weighted toward the integrity of the pyramidal tract and the age of the patient, but also, although minimally, it is conditioned by GCL integrity. Finally, our outcomes suggest MS disability is better captured by SC and retinal parameters than brain atrophy, supporting the idea of pathological mechanisms at SC and retina distinct from the brain or at least, less clinically "silent" tissue injury at SC or retina than whole brain [24].…”

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability

“…In this study, the overall MTR coefficient of variation (aggregating between‐session, between‐scanner, and between‐participant variabilities) for the centered spinal cord levels C4‐C6 was about 3% (in our case, 1 pu). This value is similar to that reported in previous single‐scanner spinal cord studies (range: 1–2 pu, summarized in Supplementary Table 1), and even slightly smaller . Our result suggests that MTR values obtained using scanners from the same manufacturer with the same acquisition parameters can be used in multicenter studies without any drastic increase in the variability of the MTR measurements, relative to single‐center studies.…”