Methods for Brain Atrophy MR Quantification in Multiple Sclerosis: Application to the Multicenter INNI Dataset

Background: Current therapeutic strategies in multiple sclerosis (MS) target neurodegeneration. However, the integration of atrophy measures into the clinical scenario is still an unmet need. Purpose: To compare methods for whole-brain and gray matter (GM) atrophy measurements using the Italian Neuroimaging Network Initiative (INNI) dataset. Study type: Retrospective (data available from INNI). Population: A total of 466 patients with relapsing-remitting MS (mean age = 37.3 ± 10 years, 323 women) and 279 healthy controls (HC; mean age = 38.2 ± 13 years, 164 women). Field strength/sequence: A 3.0-T, T1-weighted (spin echo and gradient echo without gadolinium injection) and T2-weighted spin echo scans at baseline and after 1 year (170 MS, 48 HC). Assessment: Structural Image Evaluation using Normalization of Atrophy (SIENA-X/XL; version 5.0.9), Statistical Parametric Mapping (SPM-v12); and Jim-v8 (Xinapse Systems, Colchester, UK) software were applied to all subjects. Statistical tests: In MS and HC, we evaluated the intraclass correlation coefficient (ICC) among FSL-SIENA(XL), SPM-v12, and Jim-v8 for cross-sectional whole-brain and GM tissue volumes and their longitudinal changes, the effect size according to the Cohen's d at baseline and the sample size requirement for whole-brain and GM atrophy progression at different power levels (lowest = 0.7, 0.05 alpha level). False discovery rate (Benjamini-Hochberg procedure) correction was applied. A P value <0.05 was considered statistically significant. Results: SPM-v12 and Jim-v8 showed significant agreement for cross-sectional whole-brain (ICC = 0.93 for HC and ICC = 0.84 for MS) and GM volumes (ICC = 0.66 for HC and ICC = 0.90) and longitudinal assessment of GM atrophy (ICC = 0.35 for HC and ICC = 0.59 for MS), while no significant agreement was found in the comparisons between whole-brain and GM volumes for SIENA-X/XL and both SPM-v12 (P = 0.19 and P = 0.29, respectively) and Jim-v8 (P = 0.21 and P = 0.32, respectively). SPM-v12 and Jim-v8 showed the highest effect size for cross-sectional GM atrophy (Cohen's d = -0.63 and -0.61). Jim-v8 and SIENA(XL) showed the smallest sample size requirements for whole-brain (58) and GM atrophy (152), at 0.7 power level. Data conclusion: The findings obtained in this study should be considered when selecting the appropriate brain atrophy pipeline for MS studies. Evidence level: 4. Technical efficacy: Stage 1.