Limits of Fat Quantification in the Presence of Iron Overload

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: Cramer-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, Delta TE = 0.67 msec at 1.5 T, TE1 = 0.65 msec, Delta TE = 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 similar to 538 s(-1) and similar to 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, Delta TE = 1.01 msec compared to 3% with TE1 = 0.65 msec, Delta TE = 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. Technical Efficacy Stage: 1