Hepatic R2* is more strongly associated with proton density fat fraction than histologic liver iron scores in patients with nonalcoholic fatty liver disease

Abstract

Background The liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates. Purpose To identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD). Study Type Retrospective analysis of prospectively acquired data. Population Baseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials. Field Strength 1.5T and 3T; chemical‐shift encoded multiecho gradient echo. Assessment Correlation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI‐derived, and histological covariates of liver R2*. Statistical Tests Pearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine‐learning method. Results Hepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P < 0.0001) and at 3T (r = 0.586, P < 0.0001). In the GBM analysis, hepatic PDFF was the most influential covariate for hepatic R2*, with relative influences (RIs) of 61.3% at 1.5T and 47.5% at 3T; less influential covariates had RIs of up to 11.5% at 1.5T and 16.7% at 3T. Nonhepatocellular iron was weakly associated with R2* at 3T only (RI 6.7%), and hepatocellular iron was not associated with R2* at either field strength. Data Conclusion Hepatic PDFF is the most influential covariate for R2* at both 1.5T and 3T; nonhepatocellular iron deposition is weakly associated with liver R2* at 3T only. Level of Evidence: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1456–1466.

Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease

“…In many NAFLD patients, elevated ferritin may reflect a subclinical inflammatory state, rather than iron overload [31]. Similar to this observation, an R2* value on MRI (as an indicator of iron content) in its normal or minimally elevated range correlated more strongly with PDFF on MRI than the actual grade of hepatic iron content in patients with NAFLD [41]. Furthermore, low titers of autoimmune antibodies (in the absence of concomitant autoimmune hepatitis) are common and of no apparent clinical consequence [40].…”

“…(A, B) T1-weighted magnetic resonance images showing the automatic capturing of the liver and (C) the summary of results that shows PDFF of the whole liver (13.2%) as well as R2* value (as a marker for liver iron content). R2* values of <126 S -1 are normal at 3T scanner examination[41].…”

Magnetic resonance‐based biomarkers in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…73 This means that any intervention that alters liver glycogen stores also can induce changes in T1 independent of inflammation and fibrosis. Another potential issue is the use of R2* for correction of T1 since there is a strong dependency of R2* on liver fat as shown recently by Bashir et al 74 In fact, in this study it was shown that liver fat is the most influential covariate of hepatic R2* both at 1.5 and 3T. This means that any intervention inducing a change in liver PDFF also will induce a change in cT1 owing to the change in R2*.…”

Multiparametric MR mapping in clinical decision-making for diffuse liver disease

“…Fibrosis, fat, and other hepatic cellular pathology contribute to R2 and R2* and interfere with liver iron content estimation [ 54 – 56 ]. The effect of fat has accuracy implications in NAFLD [ 55 ] but appears to be relatively small and may be minimised by mathematical correction [ 57 , 58 ]. In, addition, R2* can be obtained simultaneously with PDFF with Dixon-based sequences [ 55 , 56 , 59 ].…”