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

J Magn Reson Imaging. 2012 Apr;35(4):844-51. doi: 10.1002/jmri.22890. Epub 2011 Nov 29.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adiposity*
  • Animals
  • Artifacts*
  • Biomarkers
  • Disease Models, Animal*
  • Fatty Liver / complications
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Humans
  • Iron Overload / complications
  • Iron Overload / metabolism
  • Iron Overload / pathology*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Triglycerides / analysis

Substances

  • Biomarkers
  • Triglycerides