Exploring the origins of echo-time-dependent quantitative susceptibility mapping (QSM) measurements in healthy tissue and cerebral microbleeds.

Quantitative susceptibility mapping (QSM) is increasingly used to measure variation in tissue composition both in the brain and in other areas of the body in a range of disease pathologies. Although QSM measurements were originally believed to be independent of the echo time (TE) used in the gradient-recalled echo (GRE) acquisition from which they are derived; recent literature (Sood et al., 2016) has shown that these measurements can be highly TE-dependent in a number of brain regions. In this work we systematically investigate possible causes of this effect through analysis of apparent frequency and QSM measurements derived from data acquired at multiple TEs in vivo in healthy brain regions and in cerebral microbleeds (CMBs); QSM data acquired in a gadolinium-doped phantom; and in QSM data derived from idealized simulated phase data. Apparent frequency measurements in the optic radiations (OR) and central corpus callosum (CC) were compared to those predicted by a 3-pool white matter model, however the model failed to fully explain contrasting frequency profiles measured in the OR and CC. Our results show that TE-dependent QSM measurements can be caused by a failure of phase unwrapping algorithms in and around strong susceptibility sources such as CMBs; however, in healthy brain regions this behavior appears to result from intrinsic non-linear phase evolution in the MR signal. From these results we conclude that care must be taken when deriving frequency and QSM measurements in strong susceptibility sources due to the inherent limitations in phase unwrapping; and that while signal compartmentalization due to tissue microstructure and content is a plausible cause of TE-dependent frequency and QSM measurements in healthy brain regions, better sampling of the MR signal and more complex models of tissue are needed to fully exploit this relationship.