Defining multiple sclerosis disease activity using MRI T2-weighted difference imaging.
Lee MA., Smith S., Palace J., Matthews PM.
Serial brain MRI scanning is widely used for assessing multiple sclerosis disease activity in the evaluation of new therapies. Traditionally, the net change in T2-weighted lesion volume between paired scans has been used as a measure of disease progression and as a secondary endpoint in definitive clinical trials. However, as the net change in T2-weighted lesion volume reflects only the difference between new and resolved T2-weighted lesions, this measure significantly under-represents the total T2-weighted lesion activity. Difference images produced by subtracting labelled T2-weighted lesion volumes from serial registered T2-weighted scans allows separate measurements of individual volumes of new and resolving T2-weighted lesions, which may reflect underlying disease activity more sensitively. We generated T2-weighted differences images to define T2-weighted lesion changes over 1 year for 19 patients with relapsing multiple sclerosis. The mean new T2-weighted lesion volume change was three times greater than the mean net T2-weighted lesion volume change over the study period. New T2-weighted lesion volumes were more strongly correlated with T1-weighted gadolinium-enhancing lesion volumes (r = 0.72, P = 0.001) than were the net T2-weighted lesion volume changes (r = 0.45, P = 0.01). Baseline T2-weighted lesion volume was more highly correlated with new T2-weighted lesion volumes (r = 0.89, P < 0.0001) than with net T2-weighted lesion change (r = 0.47, P < 0.001). There was a trend for patients who showed sustained clinical progression over the year to have a greater new T2-weighted lesion volume than those who did not. This difference was not seen with net T2-weighted lesion volume change. T2-weighted lesion difference images should provide an additional and sensitive tool for monitoring disease activity in multiple sclerosis. Independent definition of new and resolving T2-weighted lesion volumes also offers the potential for discrimination of the relative effects of experimental therapies on new inflammatory activity from the effects on oedema resolution and lesion repair.