Advances in spinal cord imaging in multiple sclerosis

Abstract

The spinal cord is frequently affected in multiple sclerosis (MS), causing motor, sensory and autonomic dysfunction. A number of pathological abnormalities, including demyelination and neuroaxonal loss, occur in the MS spinal cord and are studied in vivo with magnetic resonance imaging (MRI). The aim of this review is to summarise and discuss recent advances in spinal cord MRI. Advances in conventional spinal cord MRI include improved identification of MS lesions, recommended spinal cord MRI protocols, enhanced recognition of MRI lesion characteristics that allow MS to be distinguished from other myelopathies, evidence for the role of spinal cord lesions in predicting prognosis and monitoring disease course, and novel post-processing methods to obtain lesion probability maps. The rate of spinal cord atrophy is greater than that of brain atrophy (−1.78% versus −0.5% per year), and reflects neuroaxonal loss in an eloquent site of the central nervous system, suggesting that it can become an important outcome measure in clinical trials, especially in progressive MS. Recent developments allow the calculation of spinal cord atrophy from brain volumetric scans and evaluation of its progression over time with registration-based techniques. Fully automated analysis methods, including segmentation of grey matter and intramedullary lesions, will facilitate the use of spinal cord atrophy in trial designs and observational studies. Advances in quantitative imaging techniques to evaluate neuroaxonal integrity, myelin content, metabolic changes, and functional connectivity, have provided new insights into the mechanisms of damage in MS. Future directions of research and the possible impact of 7T scanners on spinal cord imaging will be discussed.

Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral

“…ANN NEUROL 2019;86:704-713 S pinal cord atrophy on magnetic resonance imaging (MRI) is a marker of neurodegeneration in multiple sclerosis (MS), 1,2 and is one of the main substrates of longterm disease progression. [3][4][5][6][7][8][9][10][11] Spinal cord atrophy progresses faster than brain atrophy (1.7%/year vs 0.4-0.6%/year), is greater in progressive MS than in the relapsing forms of MS, and predicts disability. 5,12,13 It is crucial to obtain an accurate and precise longitudinal measurement of spinal cord atrophy, because it could be used to monitor disease progression and become a primary outcome measure in phase 2 clinical trials with neuroprotective therapies, not only in MS, but also in other neurodegenerative disorders.…”

“…[14][15][16][17] Spinal cord atrophy is conventionally estimated with segmentation-based methods (eg, cervical cord cross-sectional area [CSA]), applied to volumetric spinal cord images, 18 that measure cord characteristics at each time point; indirect longitudinal atrophy measurements are obtained by numerical subtraction, with relatively low reproducibility and responsiveness to change. 6,19 In contrast, longitudinal brain atrophy measurements are nowadays based on registration-based techniques that significantly reduce measurement noise. 20 Based on this, we evaluated a registration-based method used for brain atrophy, to measure longitudinal spinal cord atrophy; in this method, named generalized boundary shift integral (GBSI), atrophy is directly measured from the probabilistic boundary-shift region of interest, adaptively estimated between 2 time points.…”

Considerations for Mean Upper Cervical Cord Area Implementation in a Longitudinal MRI Setting: Methods, Interrater Reliability, and MRI Quality Control

“…[6][7][8] MUCCA has been found to be robust at the C1-C2 and C2-C3 intervertebral levels. 9,10 However, there is little consensus on how reliable it is longitudinally or whether SC atrophy measures are ready for use as a clinical trial end point and/or for patient monitoring in neuroinflammatory diseases, 11,12 SC injury, 13,14 or degenerative cervical myelopathy, 15 among other diseases affecting the SC. Most studies of MR imaging-based SC atrophy comparisons of diseased with healthy SC measures have relied on interindividual variability calculated from crosssectional data.…”

“…16 Intraindividual variability in healthy participants (HP) is often ignored or assumed to be equivalent to the mean change (or SD) in SC atrophy measures. 9 The utility of using cerebral 3D MRIs, including the upper cervical cord (UCC), as a source of MUCCA calculations is based on the availability of this sequence in most patients. These scans can be used for both detection of abnormalities in the brain and the retrospective analysis of SC atrophy.…”

Diagnosis and management of multiple sclerosis: MRI in clinical practice

“…When the suspicion of clinically isolated syndrome (CIS) or of MS is raised, both brain and spinal cord scans should be requested [2,11]. As well as providing information regarding lesion dissemination in space, spinal cord MRI is also valuable for differential diagnosis, when uncertainty exists over the nature of brain lesions [12,13].…”