Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis

Abstract

Objective: To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials.

Methods: A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts by atlas-based tractography. Linear mixed-effect models estimated annualized rates of change for each index, and sample size estimates for potential clinical trials were determined.

Results: There were significant changes over time in fractional anisotropy and perpendicular diffusivity in the supratentorial brain and corpus callosum, mean diffusivity in the supratentorial brain, and magnetization transfer ratio in all areas studied. Changes were most rapid in the corpus callosum, where fractional anisotropy decreased 1.7% per year, perpendicular diffusivity increased 1.2% per year, and magnetization transfer ratio decreased 0.9% per year. The T2 relaxation time changed more rapidly than diffusion tensor imaging indices and magnetization transfer ratio but had higher within-participant variability. Magnetization transfer ratio in the corpus callosum and supratentorial brain declined at an accelerated rate in progressive MS relative to relapsing-remitting MS. Power analysis yielded reasonable sample sizes (on the order of 40 participants per arm or fewer) for 1- or 2-year trials.

Conclusions: Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.

Figure 1. Longitudinal change in fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum

Spaghetti plots demonstrate longitudinal changes in FA (A) and MTR (C) in the corpus callosum within individuals. Cross-participant mean FA (B) and MTR (D) values at yearly intervals from baseline demonstrate longitudinal decline in the measured values. Error bars represent 95% confidence intervals. Larger error bars in the year 3 results probably reflect smaller sample sizes.