Can transverse relaxation rates in deep gray matter be approximated from functional and T2-weighted FLAIR scans for relative brain iron quantification?

Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R2∗ transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R2∗ rates using metrics derived from fMRI-EPI and T2-weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (vEPI and vFLAIR), as well as R2∗ rates and QSM estimates, and found significant correlations between vEPI and vFLAIR and R2∗ rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing vEPI and vFLAIR with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R2∗ rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T2-weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest.