Multi-compartment relaxometry and diffusion informed myelin water imaging – Promises and challenges of new gradient echo myelin water imaging methods

Myelin water fraction (MWF) mapping based on data fitting of a 3-pool exponential model of multi-echo gradient echo (mGRE) data using MRI shows great promises for in vivo myelin quantification. However, this multi-exponential fitting is ill-conditioned because of the similar relaxation times and frequency shifts of the various compartments. Additionally, the bound water residing in the myelin sheath of white matter is expected to have a faster longitudinal magnetisation recovery than that of the free water in the axonal and extracellular space. When the Ernst angle is used to achieve maximum SNR and improve fitting, this will introduce a T1-weighting effect to the derived MWF. In this study, we first demonstrate that diffusion-weighted imaging can be used to infer the compartmental signal properties using an analytical fibre model to achieve a robust MWF estimation. Second, we show that by incorporating a variable flip angle scheme to the mGRE acquisition with a multi-compartment relaxometry model, not only the MWF is corrected from the T1 dependency but also the fitting procedure becomes less ill-conditioned and more SNR efficient. Finally, we demonstrate these two approaches can be combined allowing higher spatial resolution MWF maps than what has been reported to date with robust MWF estimation on a small cohort.