Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers

Abstract

Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the “proton density fat-fraction” (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5T in 13 explanted human livers. We performed co-localized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117), tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction and histology. Intra-observer agreement, inter-observer agreement and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984; CI: 0.978–0.989) and strong correlation with histology (r=0.850; CI: 0.791–0.894) and triglyceride extraction (r=0.871; CI: 0.818–0.909). Intra-observer agreement, inter-observer agreement and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all p<0.001). Conclusion MRI-PDFF is an accurate, precise and reader-independent non-invasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.

Quantification of liver proton-density fat fraction in 7.1T preclinical MR systems: Impact of the fitting technique

“…With both PDFF reconstruction techniques investigated here, we found strong correlations between PDFF and these two gold standards. This correlation at 7.1 Tesla MR imaging is comparable to the correlations between PDFF derived from images acquired with less than 3 Tesla and histopathology as well as triglyceride content found in earlier studies (24-27). These results corroborate that quantification of liver fat using a preclinical 7.1 Tesla MR system is feasible.…”

Quantitative Imaging Biomarkers of NAFLD

“…PDFF measured by MRI and MRS has been confirmed to be equivalent and interchangeable in the NAFLD population [50–52]. It agrees closely to known and biochemically measured triglyceride concentrations in phantoms [53, 54] and in human liver samples [55]. It is also highly correlated with tissue histological grades in animal models of NAFLD [56, 57], as well as human subjects with NAFLD [58–60].…”

“…These are important features of a biomarker to facilitate generalization of results from single-site studies, as well as combining data from multiple sites in multicenter studies or in meta-analyses. Compared to histopathological analysis, a distinct advantage of PDFF as an outcome metric in longitudinal studies is the ability to measure objectively the changes on a continuous scale in each subject (i.e., ± x % in absolute PDFF), which is superior to histological grading using subjective assignment of a discrete severity bracket [55]. The overall reproducibility (i.e., between-examination measurement 95 % confidence interval) of PDFF has been reported ±1.8 %, implying a change in PDFF exceeding this threshold can be considered a real effect [68].…”

Imaging-Based Assessment of Steatosis, Inflammation and Fibrosis in NAFLD

“…MRI-PDFF also had good inter-examination accuracy for whole liver assessment (ICC = 0.999; SD < 0.24%, range < 0.45%) [28]. Furthermore, MRI-PDFF was shown to have better inter-and intra-observer agreement compared with histological steatosis grading (p < 0.001) [29].…”