On the performance of multi-compartment relaxometry for myelin water imaging (MCR-MWI) – test-retest repeatability and inter-protocol reproducibility

In this study, we optimized the variable flip angle (VFA) acquisition scheme using numerical simulations to shorten the acquisition time of multicompartment relaxometry for myelin water imaging (MCR-MWI) to a clinically practical range in the absence of advanced image reconstruction methods. As the primary objective of this study, the test-retest repeatability of myelin water fraction (MWF) measurements of MCR-MWI is evaluated on three gradient echo (GRE) sequence settings using the optimized VFA schemes with different echo times and repetition times, emulating various scanner setups. The cross-protocol reproducibility of MCR-MWI and MCR with diffusion-informed myelin water imaging (MCR-DIMWI) is also examined. As a secondary objective, we explore the bundle-specific profiles of various microstructural parameters from MCR-(DI)MWI and their cross-correlations to determine if these parameters possess supplementary microstructure information beyond myelin concentration.Numerical simulations indicate that MCR-MWI can be performed with a minimum of three flip angles covering a wide range of T1 weightings without adding significant bias. This is supported by the results of an in vivo experiment, allowing whole-brain 1.5 mm isotropic MWF maps to be acquired in 9 min, reducing the total scan time to 40% of the original implementation without significant quality degradation. Good test-retest repeatability is observed for MCR-MWI for all three GRE protocols. While good correlations can also be found in MWF across protocols, systematic differences are observed. Bundle-specific MWF analysis reveals that certain white matter bundles are similar in all participants. We also found that microstructure relaxation parameters have low linear correlations with MWF. MCR-MWI is a reproducible measure of myelin. However, attention should be paid to the protocol related MWF differences when comparing different studies, as the MWF bias up to 0.5% can be observed across the protocols examined in this work