Conventional MRI Measures in Relation to Advanced MRI Measures in Multiple Sclerosis before and after Mesenchymal Stem Cell Transplantation

Background: Advanced MRI measures, such as diffusion tensor imaging (DTI) and cortical thickness (CTh), may better detect changes in tissue pathology in multiple sclerosis (MS) compared to conventional MRI measures and have been proposed as outcomes in clinical trials of neuroprotective and repair-promoting strategies.  However, their relationship to conventional MRI measurements is incompletely studied. 

Objectives: To assess the relationship between advanced MRI measures and conventional MRI measures in MS patients at baseline and six months after mesenchymal stem cell (MSC) transplantation.

Methods: 10 patients with relapsing-remitting (RR) and 14 with secondary progressive (SP) MS with Expanded Disability Status Scale (EDSS) of 3.0 to 6.5 were enrolled in a phase 1 study of MSC transplantation.  Conventional MRI measures (T2 lesion volume [T2LV], brain parenchymal fraction [BPF]), gray matter fraction (GMF), CTh, and DTI measures (longitudinal diffusivity [LD] and transverse diffusivity [TD]) of the corticospinal tract [CST] and lesional areas were collected at baseline, Month 3, and Month 6.  Pearson correlations with Bonferroni correction were performed at each time point. 

Results: Across all participants and time points, CTh correlated with BPF and GMF (p < 0.001).  Additionally, CTh correlated significantly with CST LD at all time points (p < 0.001) and inversely with T2LV at Month 3 (p < 0.001), but not with CST TD.  CST LD correlated with T2LV at baseline and Month 3 and inversely with BPF and GMF at all time points (for all, p < 0.001).  CST TD correlated with T2LV at baseline and Month 3 (p < 0.001), but not at Month 6 (p = 0.02). In SPMS patients, similar correlations were seen with CST LD and BPF, GMF, and T2LV at almost all time points (p < 0.001), but CST LD and T2LV did not significantly correlate at Month 6 (p = 0.06).  In RRMS, CST LD showed only a significant association with GMF at baseline (p < 0.001).  

Conclusions: CST LD was a more consistent predictor of MRI lesion burden and regional and whole brain atrophy measures before and after MSC transplantation than CST TD, particularly for patients with SPMS.  CTh and CST LD were consistently associated and may represent a more sensitive measure of disease progression than other DTI measures