The influence of brain iron on myelin water imaging

With myelin playing a vital role in normal brain integrity and function and thus in various neurological disorders, myelin sensitive magnetic resonance imaging (MRI) techniques are of great importance. In particular, multi-exponential T-2 relaxation was shown to be highly sensitive to myelin. The myelin water imaging (MWI) technique allows to separate the T-2 decay into short components, specific to myelin water, and long components reflecting the intra- and extracellular water. The myelin water fraction (MWF) is the ratio of the short components to all components. In the brain's white matter (WM), myelin and iron are closely linked via the presence of iron in the myelin generating oligodendrocytes. Iron is known to decrease T-2 relaxation times and may therefore mimic myelin. In this study, we investigated if variations in WM iron content can lead to apparent MWF changes. We performed MWI in post mortem human brain tissue prior and after chemical iron extraction. Histology for iron and myelin confirmed a decrease in iron content and no change in myelin content after iron extraction. In MRI, iron extraction lead to a decrease in MWF by 26%-28% in WM. Thus, a change in MWF does not necessarily reflect a change in myelin content. This observation has important implications for the interpretation of MWI findings in previously published studies and future research.