Test–retest reliability and concurrent validity of in vivo myelin content indices: Myelin water fraction and calibrated T1w/T2w image ratio

Abstract In an age‐heterogeneous sample of healthy adults, we examined test–retest reliability (with and without participant repositioning) of two popular MRI methods of estimating myelin content: modeling the short spin–spin (T 2 ) relaxation component of multi‐echo imaging data and computing the ratio of T 1 ‐weighted and T 2 ‐weighted images (T 1 w/T 2 w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi‐component T 2 relaxation data as a standard, we evaluate the concurrent and differential validity of T 1 w/T 2 w ratio images. The results revealed high reliability of MWF and T 1 w/T 2 w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T 1 w/T 2 w ratio in only two of six examined regions of the cerebral white matter. Notably, significant correlations of the same or greater magnitude were observed for T 1 w/T 2 w ratio and the intermediate T 2 relaxation time constant, which is believed to reflect differences in the mobility of water between the intracellular and extracellular compartments. We conclude that although both methods are highly reliable and thus well‐suited for longitudinal studies, T 1 w/T 2 w ratio has low criterion validity and may be not an optimal index of subcortical myelin content. Hum Brain Mapp 38:1780–1790, 2017 . © 2017 Wiley Periodicals, Inc.