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 fatfraction 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.