Validation of MRI biomarkers of hepatic steatosis in the presence of iron overload in the ob/ob mouse

Purpose: To validate the utility and performance of a T 2* correction method for hepatic fat quantification in an animal model of both steatosis and iron overload. Materials and Methods: Mice with low (n = 6), medium (n = 6), and high (n = 8) levels of steatosis were sedated and imaged using a chemical shift‐based fat‐water separation method to obtain magnetic resonance imaging (MRI) fat‐fraction measurements. Imaging was performed before and after each of two superparamagnetic iron oxide (SPIO) injections to create hepatic iron overload. Fat‐fraction maps were reconstructed with and without T 2* correction. Fat‐fraction with and without T 2* correction and T 2* measurements were compared after each injection. Liver tissue was harvested and imaging results were compared to triglyceride extraction and histology grading. Results: Excellent correlation was seen between MRI fat‐fraction and tissue‐based fat quantification. Injections of SPIOs led to increases in R 2* (=1/T 2*). Measured fat‐fraction was unaffected by the presence of iron when T 2* correction was used, whereas measured fat‐fraction dramatically increased without T 2* correction. Conclusion: Hepatic fat‐fraction measured using a T 2*‐corrected chemical shift‐based fat‐water separation method was validated in an animal model of steatosis and iron overload. T 2* correction enables robust fat‐fraction estimation in both the presence and absence of iron, and is necessary for accurate hepatic fat quantification. J. Magn. Reson. Imaging 2012;35:844–851. © 2011 Wiley Periodicals, Inc.