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Updated: Nov 11, 2025
Measurement of Tissue Non-Heme Iron Content using a Bathophenanthroline-Based Colorimetric Assay
Published on: January 31, 2022
Limits of Fat Quantification in the Presence of Iron Overload
Timothy J Colgan1, Ruiyang Zhao1,2, Nathan T Roberts1,2
1Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA.
Background:
Chemical shift encoded magnetic resonance imaging (CSE-MRI)-based tissue fat quantification is confounded by increased R2* signal decay rate caused by the presence of excess iron deposition.
Purpose:
To determine the upper limit of R2* above which it is no longer feasible to quantify proton density fat fraction (PDFF) reliably, using CSE-MRI.
Study Type:
Prospective.
Population:
Cramér-Rao lower bound (CRLB) calculations, Monte Carlo simulations, phantom experiments, and a prospective study in 26 patients with known or suspected liver iron overload.
Field Strength/Sequence:
Multiecho gradient echo at 1.5 T and 3.0 T.
Assessment:
CRLB calculations were used to develop an empirical relationship between the maximum R2* value above which PDFF estimation will achieve a desired number of effective signal averages. A single voxel multi-TR, multi-TE stimulated echo acquisition mode magnetic resonance spectroscopy acquisition was used as a reference standard to estimate PDFF. Reconstructed PDFF and R2* maps were analyzed by one analyst using multiple regions of interest drawn in all nine Couinaud segments.
Statistical Tests:
None.
Results:
Simulations, phantom experiments, and in vivo measurements demonstrated unreliable PDFF estimates with increased R2*, with PDFF errors as large as 20% at an R2* of 1000 s-1 . For typical optimized Cartesian acquisitions (TE1 = 0.75 msec, ΔTE = 0.67 msec at 1.5 T, TE1 = 0.65 msec, ΔTE = 0.58 msec at 3.0 T), an empirical relationship between PDFF estimation errors and acquisition parameters was developed that suggests PDFF estimates are unreliable above an R2* of ~538 s-1 and ~779 s-1 at 1.5 T and 3 T, respectively. This empirical relationship was further investigated with phantom experiments and in vivo measurements, with PDFF errors at an R2* of 1000 s-1 at 3.0 T as large as 10% with TE1 = 1.24 msec, ΔTE = 1.01 msec compared to 3% with TE1 = 0.65 msec, ΔTE = 0.58 msec.
Data Conclusion:
We successfully developed a theoretically-based empirical formula that may provide an easily calculable guideline to identify R2* values above which PDFF is not reliable in research and clinical applications using CSE-MRI to quantify PDFF in the presence of iron overload.
Level Of Evidence:
1 TECHNICAL EFFICACY STAGE: 1.
