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

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 (T₂) relaxation component of multi-echo imaging data and computing the ratio of T1-weighted and T₂-weighted images (T₁w/T₂w). Taking the myelin water fraction (MWF) index of myelin content derived from the multi-component T₂ relaxation data as a standard, we evaluate the concurrent and differential validity of T₁w/T₂w ratio images. The results revealed high reliability of MWF and T₁w/T₂w ratio. However, we found significant correlations of low to moderate magnitude between MWF and the T₁w/T₂w 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 T₁w/T₂w ratio and the intermediate T₂ 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, T₁w/T₂w ratio has low criterion validity and may be not an optimal index of subcortical myelin content.