Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study

Abstract

Background and purpose: Brain MRI-derived lesions and atrophy are related to multiple sclerosis (MS) disability. In the Serially Unified Multicenter MS Investigation (SUMMIT), from Brigham and Women's Hospital (BWH) and University of California, San Francisco (UCSF), we assessed whether MRI methodologic heterogeneity may limit the ability to pool multisite data sets to assess 5-year clinical-MRI associations.

Methods: Patients with relapsing-remitting (RR) MS (n = 100 from each site) underwent baseline brain MRI and baseline and 5-year clinical evaluations. Patients were matched on sex (74 women each), age, disease duration, and Expanded Disability Status Scale (EDSS) score. MRI was performed with differences between sites in both acquisition (field strength, voxel size, pulse sequences), and postprocessing pipeline to assess brain parenchymal fraction (BPF) and T2 lesion volume (T2LV).

Results: The UCSF cohort showed higher correlation than the BWH cohort between T2LV and disease duration. UCSF showed a higher inverse correlation between BPF and age than BWH. UCSF showed a higher inverse correlation than BWH between BPF and 5-year EDSS score. Both cohorts showed inverse correlations between BPF and T2LV, with no between-site difference. The pooled but not individual cohort data showed a link between a lower baseline BPF and the subsequent 5-year worsening in disability in addition to other stronger relationships in the data.

Conclusions: MRI acquisition and processing differences may result in some degree of heterogeneity in assessing brain lesion and atrophy measures in patients with MS. Pooling of data across sites is beneficial to correct for potential biases in individual data sets.

Keywords: MRI; Multiple sclerosis; brain; disability; multicenter study; neuroimaging.

Figure 1.

Baseline T2 lesion volume vs. EDSS score at baseline and 5-year follow-up Global cerebral T2 hyperintense lesion volume (T2LV) at baseline vs. Expanded Disability Status Scale (EDSS) score at baseline and at 5-year follow-up from the Brigham and Women’s Hospital (BWH) (top) and the University of California, San Francisco (UCSF) (bottom) cohorts. Scatter plots with regression slopes illustrate the relationship between T2LV and EDSS score at baseline (BWH: Pearson r = 0.178, p=0.077, UCSF: r = 0.207, p=0.038), and at 5-year follow-up (BWH: Pearson r = 0.237, p=0.017, UCSF: r = 0.294, p=0.003). The correlation coefficients were not different between the two cohorts at either time point (p>0.05). See also Table 2.

Figure 2.

Baseline BPF vs. EDSS score at baseline and 5-year follow-up Brain parenchymal fraction (BPF) at baseline vs. Expanded Disability Status Scale (EDSS) score at baseline and at 5-year follow-up from the Brigham and Women’s Hospital (BWH) (top) and the University of California, San Francisco (UCSF) (bottom) cohorts. Scatter plots with regression slopes illustrate the relationship between whole brain atrophy and EDSS score at baseline (BWH: Pearson r = −0.174, p=0.084, UCSF: r = −0.371, p<0.001), and at 5-year follow-up (BWH: Pearson r = −0.072, p=0.479, UCSF: r = −0.366, p<0.001). The correlation coefficients were different between the two cohorts at the 5-year time point (p<0.05). See also Table 2.