Design and evaluation of quantitative MRI phantoms to mimic the simultaneous presence of fat, iron, and fibrosis in the liver

Abstract

Purpose: To design, construct, and evaluate quantitative MR phantoms that mimic MRI signals from the liver with simultaneous control of three parameters: proton-density fat fraction (PDFF), $R_2^{\ast }$ , and T₁ . These parameters are established biomarkers of hepatic steatosis, iron overload, and fibrosis/inflammation, respectively, which can occur simultaneously in the liver.

Methods: Phantoms including multiple vials were constructed. Peanut oil was used to modulate PDFF, MnCl₂ and iron microspheres were used to modulate $R_2^{\ast }$ , and NiCl₂ was used to modulate the T₁ of water (T_1,water ). Phantoms were evaluated at both 1.5 T and 3 T using stimulated-echo acquisition-mode MRS and chemical shift-encoded MRI. Stimulated-echo acquisition-mode MRS data were processed to estimate T_1,water , T_1,fat , $R_{2,\text{water}}^{\ast }$ , and $R_{2,\text{fat}}^{\ast }$ for each vial. Chemical shift-encoded MRI data were processed to generate PDFF and $R_2^{\ast }$ maps, and measurements were obtained in each vial. Measurements were evaluated using linear regression and Bland-Altman analysis.

Results: High-quality PDFF and $R_2^{\ast }$ maps were obtained with homogeneous values throughout each vial. High correlation was observed between imaging PDFF with target PDFF (slope = 0.94-0.97, R² = 0.994-0.997) and imaging $R_2^{\ast }$ with target $R_2^{\ast }$ (slope = 0.84-0.88, R² = 0.935-0.943) at both 1.5 T and 3 T. The values of $R_{2,\text{fat}}^{\ast }$ and $R_{2,\text{water}}^{\ast }$ were highly correlated with slope close to 1.0 at both 1.5 T (slope = 0.90, R² = 0.988) and 3 T (slope = 0.99, R² = 0.959), similar to the behavior observed in vivo. The value of T_1,water (500-1200 ms) was controlled with varying NiCl₂ concentration, while T_1,fat (300 ms) was independent of NiCl₂ concentration.

Conclusion: Novel quantitative MRI phantoms that mimic the simultaneous presence of fat, iron, and fibrosis in the liver were successfully developed and validated.

Keywords: ${\mathrm{R}}_2^{\ast }$; T1; liver; phantom; proton-density fat fraction; quantitative imaging biomarkers.