Sensitivity of quantitative relaxometry and susceptibility mapping to microscopic iron distribution

Abstract

Purpose: Determine the impact of the microscopic spatial distribution of iron on relaxometry and susceptibility-based estimates of iron concentration.

Methods: Monte Carlo simulations and in vitro experiments of erythrocytes were used to create different microscopic distributions of iron. Measuring iron with intact erythrocyte cells created a heterogeneous distribution of iron, whereas lysing erythrocytes was used to create a homogeneous distribution of iron. Multi-echo spin echo and spoiled gradient echo acquisitions were then used to estimate relaxation parameters ( $R_2$ and $R_2^{*}$ ) and susceptibility.

Results: Simulations demonstrate that $R_2$ and $R_2^{*}$ measurements depend on the spatial distribution of iron even for the same iron concentration and volume susceptibility. Similarly, in vitro experiments demonstrate that $R_2$ and $R_2^{*}$ measurements depend on the microscopic spatial distribution of iron whereas the quantitative susceptibility mapping (QSM) susceptibility estimates reflect iron concentration without sensitivity to spatial distribution.

Conclusions: $R_2$ and $R_2^{*}$ for iron quantification depend on the spatial distribution or iron. QSM-based estimation of iron concentration is insensitive to the microscopic spatial distribution of iron, potentially providing a distribution independent measure of iron concentration.

Keywords: $R_2$ estimation; $R_2^{*}$ estimation; chemical shift-encoded MRI; iron quantification; quantitative susceptibility mapping.