Reproducibility of In Vivo Magnetic Resonance Imaging-Based Measurement of Myelin Water

Purpose: To evaluate the reproducibility of multicomponent quantitative T-2 (QT2) measurements, in particular the myelin water fraction (MWF), to determine the sensitivity of this method for monitoring myelin changes in longitudinal studies and to provide a basis for correctly powering such studies. Materials and Methods: The de facto standard 32-echo spin-echo imaging sequence was used throughout, and data were analyzed using regularized non-negative least squares (NNLS) to produce T-2 distributions. Three studies were conducted in healthy subjects. First, two acquisition protocols were compared in 10 subjects. Second, variability of QT2 was evaluated over same-day scan-rescan experiments in 6 subjects. Finally, variability was quantified in a longitudinal study of 5 subjects. Results: A within-subject coefficient of variation (Coy) of 12% (range 4-25%) was observed for the MWF in brain white matter (WM) regions of interest (ROIs). The geometric mean T-2 was more stable, with a longitudinal Coy of 4% (range 1-6%). The choice of the geometry and repetition time of the acquisition protocol influenced the estimates of the MWF and T-2 values. The choice of integration range for the short-T-2 component had a significant effect on MWF estimates, but not on reproducibility. Conclusion: The reproducibility of QT2 measurements using existing methods is moderate and the method can be used in longitudinal studies, with careful consideration of the methodologic variability and an appropriate group size.