Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging

Biomed Res Int. 2017:2017:8720367. doi: 10.1155/2017/8720367. Epub 2017 Jan 18.

Abstract

Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2 may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2 in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 -/-) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2 correlate differently to disease severity and etiology of liver fibrosis. T2 shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 -/- mice. Measurements of T1 and T2 may therefore facilitate discrimination between different stages and causes of liver fibrosis.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP-Binding Cassette Sub-Family B Member 4
  • Animals
  • Carbon Tetrachloride Poisoning / diagnostic imaging*
  • Carbon Tetrachloride Poisoning / genetics
  • Carbon Tetrachloride Poisoning / metabolism
  • Disease Models, Animal
  • Humans
  • Liver / diagnostic imaging*
  • Liver / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / diagnostic imaging*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout

Substances

  • ATP Binding Cassette Transporter, Subfamily B