In vivo detection of metabolic changes by ¹ H-MRS in the DEN-induced hepatocellular carcinoma in wistar rat

Purpose: To investigate the serial changes of the hepatic metabolites in a chemical-induced rat model of hepatocellular carcinoma (HCC) in vivo by a clinical 1.5 T MR scanner. Methods: Diethyl nitrosamine (DEN) induced HCC model rats (n=60) and control rats (n=20) were included. From week 7 to week 20 after DEN administration, every other week 10–12 animals (8–9 treated and 2–3 controls) were randomly scanned before being sacrificed. According to the pathologic changes, the whole process of tumorigenesis was divided into early and late periods (week 7–13 and week 14–20, respectively). The serial hepatic changes were tested by both routine MRI and single voxel ¹H-MRS and compared with pathological results. Point resolved spectroscopy sequence (PRESS) was used for the location in MRS. The integrations of lipid- and choline-containing metabolites were calculated and analyzed. Results: All of the listed tests were fully finished in 66 rats (48 treated and 18 controls). Of the MRS curves, 65.2% (43/66) could be analyzed (mainly with resistant baseline with peaks appearing at right positions). From those qualified MRS curves, there were up to seven peaks which could be identified. The peaks of methylene lipids and methyl lipids were combined together in most cases and became the most notable component. The relative integrals of the combined lipid peak and that of the choline-containing compounds in different groups and stages were measured. Comparing with that of the controls of the same stage, the lipid of treated rats decreased in the late stage, and the choline-containing compounds increased in the same stage. Statistically significant differences were found (P<0.05) for the integrals of the lipid and the choline-containing metabolites between treated and controls in the late stage. Conclusions: Our initial studies for the integrals of the lipid compounds and the choline-containing metabolites might be useful for a better understanding of the metabolic activity of this DEN-induced rat HCC model.