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

Abstract

Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 andT2⁎may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 andT2⁎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 ofT2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4per 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 andT2⁎correlate differently to disease severity and etiology of liver fibrosis.T2⁎shows significant decrease correlating with fibrosis in CCl4treated animals, while demonstrating significant increase with disease severity inAbcb4 -/-mice. Measurements of T1 andT2⁎may therefore facilitate discrimination between different stages and causes of liver fibrosis.