Whole brain and deep gray matter atrophy detection over 5 years with 3T MRI in multiple sclerosis using a variety of automated segmentation pipelines

BACKGROUND: Cerebral atrophy is common in multiple sclerosis (MS) and selectively involves gray matter (GM). Several fully automated methods are available to measure whole brain and regional deep GM (DGM) atrophy from MRI. OBJECTIVE: To assess the sensitivity of fully automated MRI segmentation pipelines in detecting brain atrophy in patients with relapsing-remitting (RR) MS and normal controls (NC) over five years. METHODS: Consistent 3D T1-weighted sequences were performed on a 3T GE unit in 16 mildly disabled patients with RRMS and 16 age-matched NC at baseline and five years. All patients received disease-modifying immunotherapy on-study. Images were applied to two pipelines to assess whole brain atrophy [brain parenchymal fraction (BPF) from SPM12; percentage brain volume change (PBVC) from SIENA] and two other pipelines (FSL-FIRST; FreeSurfer) to assess DGM atrophy (thalamus, caudate, globus pallidus, putamen). MRI change was compared by two sample t-tests. Expanded Disability Status Scale (EDSS) and timed 25-foot walk (T25FW) change was compared by repeated measures proportional odds models. RESULTS: Using FreeSurfer, the MS group had a ~10-fold acceleration in on-study volume loss than NC in the caudate (mean decrease 0.51 vs. 0.05 ml, p = 0.022). In contrast, caudate atrophy was not detected by FSL-FIRST (mean decrease 0.21 vs. 0.12 ml, p = 0.53). None of the other pipelines showed any difference in volume loss between groups, for whole brain or regional DGM atrophy (all p>0.38). The MS group showed on-study stability on EDSS (p = 0.47) but slight worsening of T25FW (p = 0.054). CONCLUSIONS: In this real-world cohort of mildly disabled treated patients with RRMS, we identified ongoing atrophy of the caudate nucleus over five years, despite the lack of any significant whole brain atrophy, compared to healthy controls. The detectability of caudate atrophy was dependent on the MRI segmentation pipeline employed. These findings underscore the increased sensitivity gained when assessing DGM atrophy in monitoring MS.