Segmentation of magnetization transfer ratio lesions for longitudinal analysis of demyelination and remyelination in multiple sclerosis

We demonstrate a new technique to quantify longitudinal changes in magnetization transfer ratio (MTR) magnetic resonance imaging (MRI). These changes are indicative of demyelination and remyelination. This technique comprises a definition of ΔMTR lesions, which are identified directly from the MTR images, and an automatic procedure for segmenting these lesions. We used this technique to analyze MTR changes in lesions of subjects with rapidly progressing multiple sclerosis before and after treatment with immunoablation and autologous stem cell transplant. Subjects who experienced clinical improvement after treatment showed significantly improved MTR recovery in lesions that were recovering during treatment (p < 0.0001) while those who were clinically stable after treatment showed significantly poorer MTR recovery (p = 0.002). The statistical power of this technique to detect treatment effects on MTR recovery was shown to be considerably better than previous methods. These results suggest that longitudinal measurements of MTR in ΔMTR lesions may be an important technique for the assessment of treatment effects on remyelination in clinical trials.