Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

Marcello Moccia, Nicola Valsecchi, Olga Ciccarelli, Ronald van Schijndel, Frederik Barkhof*, Ferran Prados

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: We aimed to evaluate the implications for clinical trial design of the generalised boundary-shift integral (GBSI) for spinal cord atrophy measurement. Methods: We included 220 primary-progressive multiple sclerosis patients from a phase 2 clinical trial, with baseline and week-48 3DT1-weighted MRI of the brain and spinal cord (1 × 1 × 1 mm3), acquired separately. We obtained segmentation-based cross-sectional spinal cord area (CSA) at C1-2 (from both brain and spinal cord MRI) and C2-5 levels (from spinal cord MRI) using DeepSeg, and, then, we computed corresponding GBSI. Results: Depending on the spinal cord segment, we included 67.4–98.1% patients for CSA measurements, and 66.9–84.2% for GBSI. Spinal cord atrophy measurements obtained with GBSI had lower measurement variability, than corresponding CSA. Looking at the image noise floor, the lowest median standard deviation of the MRI signal within the cerebrospinal fluid surrounding the spinal cord was found on brain MRI at the C1-2 level. Spinal cord atrophy derived from brain MRI was related to the corresponding measures from dedicated spinal cord MRI, more strongly for GBSI than CSA. Spinal cord atrophy measurements using GBSI, but not CSA, were associated with upper and lower limb motor progression. Discussion: Notwithstanding the reduced measurement variability, the clinical correlates, and the possibility of using brain acquisitions, spinal cord atrophy using GBSI should remain a secondary outcome measure in MS studies, until further advancements increase the quality of acquisition and reliability of processing.
Original languageEnglish
Article number102418
JournalNeuroImage: Clinical
Publication statusPublished - 1 Jan 2020

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