Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies

Abstract

Background Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). Purpose To compare a new, registration‐based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. Study Type Retrospective. Subjects Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. Field Strength/Sequence 3D T1‐weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). Assessment Percentage cord area changes (PCACs) between baseline and follow‐up (cohort I: 2.34 years [interquartile range = 2.00–2.55 years], cohort II: 1.05 years [interquartile range = 1.01–1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow‐up straightened cord images, followed by AS‐based optimized cord segmentation. A subset of studies was analyzed twice by two observers. Statistical Tests Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed‐effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 − β = 0.80). Results Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was −1.12% (SE = 0.22) with Reg, −1.32% (SE = 0.30) with AS, and −1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was −0.83% (SE = 0.25) with Reg, −0.92% (SE = 0.32) with AS, and −1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra‐ and inter‐observer agreement range was 0.72–0.91 with AS, and it was >0.96 with Reg. Data Conclusion The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. Level of Evidence 3 Technical Efficacy Stage 2

Early Spinal Cord Pseudoatrophy in Multiple Sclerosis and their Treatment Through Interferon Beta

“…It was demonstrated that progressing MS and RRMS patients had opposing effects on SC volume. They illustrated the drift towards larger cervical cord volumes in RRMS patients exclusively, which they interpreted as expansions owing to inflammation or edema that would disguise real atrophy [16][17] . SC atrophy appeared to be more pronounced than brain atrophy, indicating higher susceptibility towards pathogenic alterations in MS, as evidenced through a significantly deteriorated SC.…”

Reliability of spinal cord measures based on synthetic T1-weighted MRI derived from multiparametric mapping (MPM)

“…Healthy controls showed changes in CSA of up to -0.7% over 2 years (difference between baseline and 2-year follow-up), which might be due to aging ( Papinutto et al, 2015 ), natural fluctuations, test-retest variability, or remaining effects of the scanner upgrade. Ultimately, this would limit the ability to detect subtle changes in CSA in diseases where expected effect sizes are rather small such as multiple sclerosis ( Prados et al, 2020 ;Valsasina et al, 2022 ).…”

Early spinal cord pseudoatrophy in interferon‐beta‐treated multiple sclerosis

“…Regarding technical limitations of this study, dedicated longitudinal methods for the assessment of SC atrophy rates should preferably be used in future studies. Recently developed registration-based methods for measuring longitudinal volume changes could increase reliability [34,41].…”