Magnetic resonance imaging protocol

MRI exams were performed at baseline and at week 24 to measure PDFF as a noninvasive indicator of liver fat content using a previously described, validated and reproducible technique that estimates PDFF [Reeder et al. 2009; Hines et al. 2011; Permutt et al. 2012; Tang et al. 2013, 2015]. In brief, this advanced technique utilizes a gradient echo sequence with low flip angle to minimize T1 bias and acquires multiple echoes at echo times at which fat and water signals are nominally in phase or out of phase with each other. The acquired source images are processed through an algorithm that, pixel by pixel, corrects for the T2* signal decay and multi-fat-peak spectral interference effects that confound results of conventional MRI examinations. The resulting parametric PDFF map illustrates fat distribution and quantity across the entire liver. Hepatic fat quantification via MRI-PDFF has been previously shown to be sensitive in detecting liver fat changes and has been utilized in NASH clinical trials for quantitative fat assessment [Le et al. 2012; Permutt et al. 2012; Doycheva et al. 2015; Loomba et al. 2015; Zarrinpar et al. 2015].

All MRI-PDFF parametric maps were analyzed under the supervision of an experienced hepatoradiologist (Claude Sirlin) [Hines et al. 2011; Kang et al. 2011] who was blinded to clinical and histological data, and order of scan. Trained image analysts placed regions of interest (ROIs) about 300–400 mm² in area in each of the nine liver segments while carefully evading blood vessels, bile ducts and artifacts in the region. To quantify longitudinal hepatic fat content changes between the baseline exam and follow-up exam, ROIs in each segment were colocalized using anatomic landmarks on maps obtained at each time point, and PDFF change in each segment was calculated.