Susceptibility Source Separation Unveils Paramagnetic and Diamagnetic Trajectories in Healthy Brains From 5 to...

Susceptibility source separation (SSS) enables independent evaluation of both paramagnetic iron and diamagnetic myelin in the human brain. The aim of this work was to analyze healthy brain lifespan trajectories of paramagnetic and diamagnetic susceptibilities in deep gray matter (DGM) and white matter (WM) from a large database (339 subjects, 5 to 90 years), all acquired at 3 T on the same scanner, using χ-separation and comparing it to two other common SSS methods (χ-sepnet and APART-QSM). A 3D multiple echo gradient echo sequence was used to measure phase, R2* and QSM, as well as dual echo fast spin echo to measure R2. The mean value of WM and DGM regions was calculated for SSS output maps and plotted against age to evaluate trajectories across the lifespan. With χ-separation, most DGM regions showed an increasing trend with age in the paramagnetic map, except for thalamus, which showed an inverted-U quadratic trajectory, and all DGM regions showed an increase in diamagnetic content with age. In WM, for the paramagnetic maps, body of corpus callosum, splenium and corticospinal tract showed an inverted quadratic trajectory, cingulum an increasing exponential, while no significant changes were seen in genu. For the diamagnetic WM maps, all regions followed a similar trajectory, increase in early life, peak around 40 to 60 years, and decrease with age. The different SSS approaches yielded different curve shapes and mean values in many instances. For example, APART-QSM had consistently lower ppb values, χ-sepnet had biologically unexpected results for early ages, and χ-separation data had higher standard deviation of best-fit residuals when compared to the other evaluated methods for all analyzed regions and maps. All SSS methods enabled depiction of independent iron and myelin trends; however, different results between methods suggest caution in choosing SSS methods and the need for further methodological advances.