Optimized multi-echo gradient echo MRI of the lumbosacral spinal cord to investigate atrophy, lesions, and disability in relapsing-remitting multiple sclerosis

Abstract

The lumbosacral enlargement (LSE) of the spinal cord is understudied in people with multiple sclerosis (pwMS), and there is not a consensus on the impact of age, sex, height, or weight on MRI-derived morphometrics in this region. The LSE is relevant to study in pwMS as it is involved in the control of motor and sensory functions of the lower limbs and autonomic functions which are commonly affected in MS. This study aimed to characterize biological variability of morphometric measures of the LSE cord and gray matter in healthy controls (HCs), compare these measures between HCs and people with relapsing-remitting MS (pwRRMS), and assess correlations between morphometrics and lower extremity disability and bladder symptoms in pwRRMS. An optimized T2*-weighted, axial multi-echo gradient echo anatomical MRI scan was acquired at 3T, images were automatically segmented and whole-cord and gray matter cross sectional areas for the lumbosacral spinal levels of 60 HCs and 42 pwRRMS were computed. We observed no significant main effects of age, height, weight, or sex on LSE whole-cord or gray matter cross-sectional areas (CSA) in HCs, but there were spinal level interactions with age and weight. We detected whole-cord and gray matter atrophy in the LSE of pwRRMS compared to HCs, and the effects of disease status on these measures were partially mitigated when controlling for MS lesion to cord CSA ratio within the LSE. There were no significant associations between LSE cross-sectional area measures and sensorimotor function, bladder symptoms, or clinical disability scores. However, vibration sensation in the great toe and Expanded Disability Status Scale (EDSS) scores were significantly associated with lesion to cord CSA ratio. Overall, this study found that there is little variability linked to age, sex, height, or weight in cross-sectional area measures for the healthy lumbosacral spinal cord, and lesions and atrophy were both detected in these spinal levels for a pwRRMS cohort. Although there were no associations between atrophy and symptoms, potentially due to the relatively low level of clinical disability in this cohort, these findings support the inclusion of the LSE in future imaging studies that aim to probe the full extent of spinal cord pathology in MS.