Simulation of a virtual liver iron overload model and R₂ * estimation using multispectral fat-water models for GRE...

R₂ *-MRI has emerged as a noninvasive alternative to liver biopsy for assessment of hepatic iron content (HIC). Multispectral fat-water R₂ * 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 R₂ *-based HIC measurements in conditions of coexisting iron overload and steatosis. However, the R₂ * 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 R₂ * 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 R₂ *-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 R₂ *-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 R₂ *-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 R₂ * 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 R₂ * and fat quantification.