Reproducibility of MRI-Determined Proton Density Fat Fraction Across Two Different MR Scanner Platforms

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) is the most common chronic liver disease in the United States (1,2). NAFLD can progress to cirrhosis and contribute to the development of cardiovascular disease, diabetes, and hepatocellular carcinoma (3). The inciting pathogenic process and histological hallmark of NAFLD is steatosis, the excessive accumulation of fat within hepatocytes (3–5), mainly as triglycerides. Steatosis is reversible and with early detection and intervention, progression to irreversible liver damage and other long-term NAFLD complications may be prevented (6,7). The current clinical gold standard for diagnosis and monitoring of steatosis is liver biopsy with histological analysis of intrahepatocellular fat accumulation (8). Due to its expense and invasiveness, however, liver biopsy is impractical for screening and repeated measurements, which has hindered progress in clinical care and research of NAFLD. An accurate noninvasive method to quantify liver fat content is needed. To address this need, advanced magnitude-based (9) and complex-based (10) chemical shift magnetic resonance imaging (MRI) fat quantification techniques have been developed to estimate liver proton density fat fraction (PDFF, defined as the proportion of mobile proton density in liver tissue attributable to fat) as a noninvasive biomarker of liver fat content (11–18). These techniques use low flip angle (relative to repetition time) to minimize T1 bias (16,19,20), acquire multiple echoes per excitation to permit correction for T2* effects (9,19,21), and address the multifrequency interference effects of fat (9,10). They quantify liver fat more accurately than conventional two-point Dixon methods (9) and in prior single-site single-scanner studies have shown high accuracy and repeatability for PDFF estimation using colocalized MR spectroscopy (MRS) as the reference standard (9,22,23). These techniques are also rapid and can evaluate the whole liver in a single breath-hold, offering important advantages over spectroscopy, which is restricted in spatial coverage and is more time-consuming. To validate MRI-determined PDFF as a biomarker for liver fat content, its reproducibility using these advanced MRI techniques must be demonstrated, in addition to accuracy and repeatability. For an MRI-based biomarker, reproducibility refers to the closeness in agreement between a series of measurements obtained from the same subject scanned under different conditions (eg, different scanners, different field strengths). The reproducibility of MRI-determined PDFF using the advanced MRI techniques has not been formally assessed—a gap in knowledge that needs to be filled before widespread clinical or research application of these techniques. To this end, we performed a prospective pilot study to assess the reproducibility of MRI-determined PDFF as a biomarker for liver fat content in human subjects. Our primary aim was to evaluate reproducibility on two scanners of different field strengths from different vendors. Our secondary aim was to confirm, using MRS-determined PDFF as reference standard, the high accuracy of MRI-determined PDFF at 1.5T and at 3T as reported previously. A magnitude-based MRI technique was used to measure MRI-determined PDFF.