3D Multi-Echo Dixon technique for simultaneous assessment of liver steatosis and iron overload in patients with chronic liver diseases: a feasibility study

Abstract

Background: Patients with chronic liver diseases (CLDs) often suffer from lipidosis or siderosis. Proton density fat fraction (PDFF) and R2* can be used as quantitative parameters to assess the fat/iron content of the liver. The aim of this study was to evaluate the influence of liver fibrosis and inflammation on the 3D Multi-echo Dixon (3D ME Dixon) parameters (MRI-PDFF and R2*) in patients with CLDs and to determine the feasibility of 3D ME Dixon technique for the simultaneous assessment of liver steatosis and iron overload using histopathologic findings as the reference standard.

Methods: Ninety-nine consecutive patients with CLDs underwent T1-independent, T2*-corrected 3D ME Dixon sequence with reconstruction using multipeak spectral modeling on a 3T MR scanner. Liver specimen was reviewed in all cases, grading liver steatosis, siderosis, fibrosis, and inflammation. Spearman correlation analysis was performed to determine the relationship between 3D ME Dixon parameters (MRI-PDFF and R2*) and histopathological and biochemical features [liver steatosis, iron overload, liver fibrosis, inflammation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)]. Multiple regression analysis was applied to identify variables associated with 3D ME Dixon parameters. Receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of these parameters to differentiate liver steatosis or iron overload.

Results: In multivariate analysis, only liver steatosis independently influenced PDFF values (R2=0.803, P<0.001), liver iron overload and fibrosis influenced R2* values (R2=0.647, P<0.001). The Spearman analyses showed that R2* values were moderately correlated with fibrosis stages (r=0.542, P<0.001) in the subgroup with the absence of iron overload. The area under the ROC curve of PDFF was 0.989 for the diagnosis of steatosis grade 1 or greater, and 0.986 for steatosis grade 2 or greater. The area under the ROC curve of R2* was 0.815 for identifying iron overload grade 1 or greater, and 0.876 for iron overload grade 2 or greater.

Conclusions: 3D Multi-Echo Dixon can be used to simultaneously evaluate liver steatosis and iron overload in patients with CLDs, especially for quantification of liver steatosis. However, liver R2* value may be affected by the liver fibrosis in the setting of CLDs with absence of iron overload.

Keywords: Magnetic resonance imaging; chronic liver disease (CLD); iron overload; steatosis.

Figure 1

MRI-PDFF (A) and R2* (B) maps of a 45-year-old woman with NAFLD (liver steatosis grade 2, iron grade 1, fibrosis stage 2 and inflammation grade 1) determined by histologic validation. Four largest-fit ROIs (one per the right lobe anterior, right lobe posterior, left lobe medial, and left lobe lateral segment) were manually positioned in the homogeneous liver parenchyma at the level of the right main portal vein. MRI-PDFF and R2* values were directly derived by drawing ROI on the related parameter maps. NAFLD, nonalcoholic fatty liver disease; ROI, region of interest; PDFF, proton density fat fraction.

Figure 2

Box and whisker plot shows MR-PDFF (A) and R2* (B) is higher with progressively larger histological grade. Significant differences were found in all pairwise comparisons by using the Mann-Whitney test with Bonferroni correction (all P<0.005). PDFF, proton density fat fraction.

Figure 3

Receiver operating characteristic curve (ROC) of MRI-PDFF for the identification of mild grade steatosis or higher (≥ grade 1) (A) and moderate grade or higher (≥ grade 2) (B). PDFF, proton density fat fraction.

Figure 4

Receiver operating characteristic curve (ROC) of R2* for the identification of mild grade iron overload or higher (≥ grade 1) (A) and moderate grade or higher (≥ grade 2) (B).