On the performance of multi-compartment relaxometry for myelin water imaging - Intra-subject and inter-protocol reproducibility

We evaluate the test-retest repeatability and study the tissue properties of multicompartment relaxometry-based myelin water imaging (MCR-MWI) derived from different gradient echo (GRE) acquisition settings. Additionally, the variable flip angle acquisition scheme is optimised based on numerical simulations to reduce the acquisition time of MCR-MWI in a clinically practical range without using advanced image acquisition methods. For the test-retest analysis, in vivo imaging was performed to collect data from three healthy volunteers in two identical sessions. Three GRE sequence settings with different echo times and repetition times imitating various scanner setups were evaluated. The in vivo data was also used to validate the optimal variable flip angle combination derived from simulations. Bundle-specific profiles of MCR-MWI derived microstructural parameters were investigated, as well as the cross-correlations of those parameters. Good cross-session repeatability is observed for MCR-MWI. While good correlations can also be found in myelin water fraction (MWF) across protocols, systematic differences, particularly for protocols with different repetition times, are observed. Numerical simulations indicate that MCR-MWI can be performed with a minimum of three flip angles covering a wide range of T1 weighting without adding significant measurement bias and the result is supported by the in vivo experiment allowing whole brain 1.5mm isotropic MWF maps to be acquired in 9 minutes. Bundles-specific MWF analysis reveals that certain white matter bundles are similar in all three participants. We also found that microstructure relaxation parameters have low correlations with MWF. MCR-MWI is a reproducible measure of myelin. However, attention should be paid to considering the protocol related MWF differences for comparison studies, especially when different repetition times are used as this can introduce biases up to 0.5% of MWF in our tested protocols. The optimised flip angle acquisition scheme can reduce the total scan time to 40% of the original implementation without significant quality degradation. Highlights- Multi-compartment relaxometry based myelin water imaging (MCR-MWI) can be performed with data comprising as few as 3 flip angles without introducing substantial bias or instability in the fitting procedure; - MCR-MWI is a reproducible measure of myelin water fraction (MWF) and incorporating DWI can further improve the measurement reproducibility; - MCR-MWI allows the acquisition of whole brain 1.5mm isotropic MWF maps in 9 minutes, even without the use of advanced model-based reconstructions; - Small MWF bias can present in cross-protocol comparison if the MT effect is not constant across GRE protocols (e.g., different TRs or flip angle combinations); - Compartmental relaxation parameters derived from MCR-MWI possess complimentary information beyond myelin water concentration.