Abstract

The enhancement characteristics and the diagnostic value of a cell-specific superparamagnetic contrast agent (NSR 0430) in different degrees of liver fibrosis and cirrhosis were experimentally studied in an animal model. Chronic liver damage was induced in rats either by oral administration of carbon tetrachloride (CCl4) for 15 weeks (n = 37) or by oral administration of thioacetamide (TAA) in drinking water for 24-26 weeks (n = 48). Twenty-six animals served as control subjects. T1 and T2 relaxation times for the liver and the spleen were measured in vitro with a spectrometer at 40 MHz. In vivo MR imaging at 1.5 T also was performed using T2-weighted turbo spin-echo sequences before and 1 hr after administration of NSR 0430. All data were correlated with the histologic degree of liver fibrosis and cirrhosis and the amount of connective tissue in the liver, which was measured morphometrically. CCl4 produced liver fibrosis in most of the animals, and TAA predominantly caused liver cirrhosis. NSR 0430 caused a T2 relaxation time decrease in the control animals by 49%; in the CCl4 group with light and moderate liver fibrosis, by 25%; in the CCl4 group with severe liver fibrosis or cirrhosis, by 16%; and in the TAA group with cirrhosis, by 30%. On the T2-weighted turbo spin-echo sequences, liver signal-to-noise ratios (SNRs) decreased after contrast agent administration in the control animals by 81% and 79%, depending on the TE parameter. In the CCl4 group, liver SNRs decreased by 96% and 61% in animals with light or moderate fibrosis and by 44% and 55% in animals with severe fibrosis or cirrhosis, depending on the TE parameter. In the TAA group, liver SNR decreased by 61% and 67%, depending on the TE parameter. Enhancement of the superparamagnetic contrast agent NSR 0430 is decreased in the presence of liver fibrosis and cirrhosis in an animal model. However, the reduced enhancement is not directly related to the degree of chronic liver damage, which limits the diagnostic value of superparamagnetic contrast agents in the assessment of chronic liver disease.

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