Evaluation of different models of experimentally induced liver cirrhosis for MRI research with correlation to histopathologic findings.
OBJECTIVE
Three models of experimentally induced liver cirrhosis were evaluated for MRI research on chronic liver disease. The influence 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 subcutaneous administration of carbon tetrachloride (CCl4) or by thioacetamide (TAA) in drinking water. On histology, the degree of liver fibrosis and cirrhosis, fatty infiltration, iron accumulation, and inflammatory changes were measured semiquantitatively. The amount of connective tissue was quantitatively determined by morphometry. The results were correlated with T1 and T2 relaxation times and signal intensities of the liver studied in vitro by relaxometry and in vivo by MRI.


RESULTS
In both groups with CCl4 administration, histology revealed different degrees of liver fibrosis and cirrhosis. Subcutaneous injection of CCl4 also resulted in increased fatty infiltration. On the contrary, TAA produced complete liver cirrhosis in all animals. Overall, there was a good correlation between the liver T2 relaxation time and the amount of connective tissue 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 correlation between the fatty infiltration and the T1 relaxation time, as well as with the liver signal intensity on the T1-weighted gradient echo sequence. An increased iron accumulation was also correlated with the degree of liver fibrosis/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 correlation between the T2 relaxation times and the degree of liver fibrosis/cirrhosis, this probably results from the associated inflammatory changes and is not caused by the increased amount of connective tissue.
Kreft
B
B
Department of Radiology, University of Bonn, Germany.
Dombrowski
F
F
Block
W
W
Bachmann
R
R
Pfeifer
U
U
Schild
H
H
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002908:Chronic Disease; D005500:Follow-Up Studies; D008099:Liver / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013853:Thioacetamide / Q000633:toxicity
D002273:Carcinogens; D013853:Thioacetamide; D002251:Carbon Tetrachloride