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.

Automated segmentation of cerebral deep gray matter from MRI scans: effect of field strength on sensitivity and reliability.

BACKGROUND: The cerebral subcortical deep gray matter nuclei (DGM) are a common, early, and clinically-relevant site of atrophy in multiple sclerosis (MS). Robust and reliable DGM segmentation could prove useful to evaluate putative neuroprotective MS therapies. The objective of the study was to compare the sensitivity and reliability of DGM volumes obtained from 1.5T vs. 3T MRI. METHODS: Fourteen patients with MS [age (mean, range) 50.2 (32.0-60.8) years, disease duration 18.4 (8.2-35.5) years, Expanded Disability Status Scale score 3.1 (0-6), median 3.0] and 15 normal controls (NC) underwent brain 3D T1-weighted paired scan-rescans at 1.5T and 3T. DGM (caudate, thalamus, globus pallidus, and putamen) segmentation was obtained by the fully automated FSL-FIRST pipeline. Both raw and normalized volumes were derived. RESULTS: DGM volumes were generally higher at 3T vs. 1.5T in both groups. For raw volumes, 3T showed slightly better sensitivity (thalamus: p = 0.02; caudate: p = 0.10; putamen: p = 0.02; globus pallidus: p = 0.0004; total DGM: p = 0.01) than 1.5T (thalamus: p = 0.05; caudate: p = 0.09; putamen: p = 0.03; globus pallidus: p = 0.0006; total DGM: p = 0.02) for detecting DGM atrophy in MS vs. NC. For normalized volumes, 3T but not 1.5T detected atrophy in the globus pallidus in the MS group. Across all subjects, scan-rescan reliability was generally very high for both platforms, showing slightly higher reliability for some DGM volumes at 3T. Raw volumes showed higher reliability than normalized volumes. Raw DGM volume showed higher reliability than the individual structures. CONCLUSIONS: These results suggest somewhat higher sensitivity and reliability of DGM volumes obtained from 3T vs. 1.5T MRI. Further studies should assess the role of this 3T pipeline in tracking potential MS neurotherapeutic effects.

Deep gray matter T2 hypointensity is present in patients with clinically isolated syndromes suggestive of multiple sclerosis.

Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p = 0.04). At the baseline, the T2 intensity of the left caudate nucleus was significantly lower (p = 0.01) in CIS patients with disease dissemination in space (DIS), but not in those without DIS, compared to the HC. The baseline T2 lesion volume, but not GM T2 hypointensity, was associated with evolution to CDMS (hazard ratio = 1.60, 95% confidence interval (CI) = 1.05-2.42; p = 0.02). In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS.