T1-induced apparent time dependence of diffusion coefficient measured with stimulated echo due to exchange with myelin water

For diffusion measurements, stimulated-echo acquisition mode (STEAM) has been widely used. To enhance sensitivity to microstructure, previous studies used STEAM to vary the diffusion time by changing the mixing time t_M. Here we show that varying t_M results in an “apparent” STEAM-measured diffusivity dependence on t_M, irrespective of genuine microstructure-specific time dependence. This effect is caused by T₁-relaxation and water exchange between myelin water and "free" water (intra- and extra-axonal water). We propose a modified Kärger model considering diffusion+T₁-relaxation+exchange, and demonstrate that exchange-induced t_M-dependence explains ~20-50% of the total diffusion time dependence, and should be considered while using STEAM.