Improving CPMG liver iron estimates with a $T_1$ -corrected proton density estimator

Purpose: CPMG spin echo acquisitions are attractive for diagnosing and monitoring liver iron concentration in iron overload disorders due to their time efficiency and potential to reveal unique information about tissue iron distribution. Clinical adoption remains low due to the insensitivity of CPMG-based $R_2$ estimates to liver iron concentration (LIC) when common fitting techniques are applied. In this work, we demonstrate that the inclusion of a proton density estimator (PDE) derived from the CPMG acquisition increase the sensitivity of CPMG $R_2$ estimates to LIC in both simulated and in-vivo human data.

Theory and methods: CPMG $R_2$ acquisitions from 50 clinically indicated MRI studies in patients with iron overload were analyzed with and without PDE constraints. Liver regions of interest were fit to monoexpontial and nonexponential signal decay equations. LIC by $R_2^{\ast }$ served as the reference standard. The observed calibration between CPMG $R_2$ values and LIC were compared to results predicted from a previously validated Monte Carlo model.

Results: The sensitivity of CPMG-derived $R_2$ triples when a proton density constraint is applied. When compared with $R_2^{\ast }$ -LIC estimates, both monoexponential and nonexponential models were unbiased but demonstrated broad 95% confidence intervals particularly for LIC values below 12 mg/g. Absolute error did not increase with LIC.

Conclusion: A proton density constraint can increase the sensitivity of CPMG-based models to iron. CPMG acquisitions are time-efficient and could potentially improve the dynamic range of single spin echo techniques as well as providing insight into tissue iron distribution.