Simulation of a virtual liver iron overload model and R 2 * estimation using multispectral fat-water models for GRE and UTE acquisitions at 1.5 T and 3 T.

R 2 *-MRI has emerged as a noninvasive alternative to liver biopsy for assessment of hepatic iron content (HIC). Multispectral fat-water R 2 * modeling techniques such as the nonlinear least squares (NLSQ) fitting and autoregressive moving average (ARMA) models have been proposed for the accurate assessment of iron overload by also considering fat, which can otherwise confound R 2 *-based HIC measurements in conditions of coexisting iron overload and steatosis. However, the R 2 * estimation by these multispectral models has not been systematically investigated for various acquisition methods in iron overload only conditions and across the full clinically relevant range of HICs (0-40 mg Fe/g dry liver weight). The purpose of this study is to evaluate the R 2 * accuracy and precision of multispectral models for various multiecho gradient echo (GRE) and ultrashort echo time (UTE) imaging acquisitions by constructing virtual iron overload models based on true histology and synthesizing MRI signals via Monte Carlo simulations at 1.5 T and 3 T, and comparing their results with monoexponential model and published in vivo R 2 *-HIC calibrations. The signals were synthesized with T E1  = 1.0 ms for GRE and T E1  = 0.1 ms for UTE acquisition for varying echo spacing, ΔT E (0.1, 0.5, 1, 2 ms), and maximum echo time, TE max (2, 4, 6, 10 ms). An iron-doped phantom study is also conducted to validate the simulation results in experimental GRE (T E1  = 1.2 ms, ΔT E  = 0.72 ms, TE max  = 6.24 ms) and UTE (T E1  = 0.1 ms, ΔT E  = 0.5 ms, TE max  = 6.1 ms) acquisitions. For GRE acquisitions, the multispectral ARMA and NLSQ models produced higher slopes (0.032-0.035) compared with the monoexponential model and published in vivo R 2 *-HIC calibrations (0.025-0.028). However, for UTE acquisition for shorter echo spacing (≤0.5 ms) and longer maximum echo time, TE max (≥6 ms), the multispectral and monoexponential signal models produced similar R 2 *-HIC slopes (1.5 T, 0.028-0.032; 3 T, 0.014-0.016) and precision values (coefficient of variation < 25%) across the full clinical spectrum of HICs at both 1.5 T and 3 T. The phantom analysis also showed that all signal models demonstrated a significant improvement in R 2 * estimation for UTE acquisition compared with GRE, confirming our simulation findings. Future work should investigate the performance of multispectral fat-water models by simulating liver models in coexisting conditions of iron overload and steatosis for accurate R 2 * and fat quantification.