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Induced Hepatic Fibrosis in Rats: Hepatic Steatosis, Macromolecule Content, Perfusion Parameters, and Their Correlations—Preliminary MR Imaging in Rats¹

¹ From the Department of Diagnostic Radiology (H.K., A.B.P., M.Q., R.T.C.), Section of Comparative Medicine (C.J.B.), and Departments of Biomedical Engineering (P.C., R.T.C.), Biology (A.L.), and Neurosurgery (R.T.C.), Yale University, New Haven, Conn; and Department of Clinical Research and Development, Pfizer, Sandwich Laboratories, Sandwich, Kent, England (M.W., P.S.M.). Received April 2, 2007; revision requested June 11; revision received July 19; accepted August 17; final version accepted November 13. Supported by a Pfizer Research Grant. Address correspondence to H.K., the Anlyan Center, MRRC, N125, Yale University School of Medicine, 300 Cedar St, PO Box 208043, New Haven, CT 06520-8043 (e-mail: hyeonjin.kim{at}yale.edu).

Purpose: To prospectively evaluate magnetic resonance (MR) imaging for the characterization of liver fibrosis by estimating fat and extracellular matrix content and hepatic perfusion parameters in CCl₄-treated rats.

Materials and Methods: The animal research protocol was approved by the Institutional Animal Care and Use Committee. Fifty-two rats (38 treated, 14 control) were included. A CCl₄ mixture was injected three times per week for 2–16 weeks. Fat-to-water ratios (FWRs) were calculated. Images were obtained with 12 saturation offset frequencies; magnetization transfer ratios (MTRs) were calculated. Distribution volume (DV), mean transit time (MTT), and portal fraction (PF) of blood inflow were calculated. For pairwise group comparisons, an unequal two-tailed Student t test was used. For pairwise correlations between variables, Pearson correlation coefficients were calculated. For multiple pairwise comparisons, Bonferroni correction was performed by adjusting the significance level ().

Results: FWR and DV were correlated with CCl₄ treatment duration from 0 through 8 weeks (r = 0.658, P < .001 and r = –0.664, P < .001, respectively; = .010). PF and MTT were correlated with CCl₄ treatment duration from 0 through 16 weeks (r = –0.483, P = .002 and r = 0.414, P = .008, respectively; = .010). DV was inversely correlated with FWR over the same period (r = –0.581, P < .001; = .007). Fibrotic rats without cirrhosis had a higher FWR and lower DV and PF (P < .001, P < .001, and P = .004, respectively; = .017) than control rats, and lower MTR, DV, and MTT (P = .014, .001, and .010, respectively; = .017) than cirrhotic rats. Cirrhotic rats had a higher FWR and a lower PF (P < .001, = .017) than control rats.

Conclusion: Magnetization transfer contrast is not a specific indicator of increased fibrosis in diseased liver; steatosis may influence some perfusion parameters.

© RSNA, 2008