Evaluation of different models of experimentally induced liver cirrhosis for MRI research with correlation to histopathologic findings

RATIONALE AND OBJECTIVES. Three models of experimentally induced liver cirr hosis were evaluated for MRI research on chronic liver disease. The influen ce of different histopathologic changes in liver fibrosis and cirrhosis on relaxation times and signal intensities was studied in vitro and in vivo. METHODS. Liver fibrosis and cirrhosis in rats was induced by oral or subcut aneous administration of carbon tetrachloride (CCl4) or by thioacetamide (T AA) in drinking water. On histology, the degree of liver fibrosis and cirrh osis, fatty infiltration, iron accumulation, and inflammatory changes were measured semiquantitatively; The amount of connective tissue was quantitati vely determined by morphometry, The results were correlated with T1 and T2 relaxation times and signal intensities of the liver studied in vitro by re laxometry and in vivo by MRI. RESULTS. In both groups with CCl4 administration, histology revealed differ ent degrees of liver fibrosis and cirrhosis, Subcutaneous injection of CCl4 also resulted in increased fatty infiltration, On the contrary, TAA produc ed complete liver cirrhosis in all animals. Overall, there was a good corre lation between the liver T2 relaxation time and the amount of connective ti ssue in liver fibrosis and cirrhosis, However, the degree of liver fibrosis and cirrhosis was also strongly correlated with the degree of inflammatory changes. In the group with CCl4 administration, there was a good correlati on between the fatty infiltration and the T1 relaxation time, as well as wi th the liver signal intensity on the TI-weighted gradient echo sequence. An increased iron accumulation was also correlated with the degree of liver f ibrosis/cirrhosis; however, there was no significant influence of the iron on relaxation times or signal intensities. CONCLUSIONS. The TAA model is easier to perform and more reliable in liver cirrhosis induction than the CCl4 models. Although there is a positive corr elation between the T2 relaxation times and the degree of liver fibrosis/ci rrhosis, this probably results from the associated inflammatory changes and is not caused by the increased amount of connective tissue.