Induced hepatic fibrosis in rats: hepatic steatosis, macromolecule content, perfusion parameters, and their correlations--preliminary MR imaging in rats

Radiology. 2008 Jun;247(3):696-705. doi: 10.1148/radiol.2473070605. Epub 2008 Apr 10.

Abstract

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 CCl(4)-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 CCl(4) 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 (alpha).

Results: FWR and DV were correlated with CCl(4) treatment duration from 0 through 8 weeks (r = 0.658, P < .001 and r = -0.664, P < .001, respectively; alpha = .010). PF and MTT were correlated with CCl(4) treatment duration from 0 through 16 weeks (r = -0.483, P = .002 and r = 0.414, P = .008, respectively; alpha = .010). DV was inversely correlated with FWR over the same period (r = -0.581, P < .001; alpha = .007). Fibrotic rats without cirrhosis had a higher FWR and lower DV and PF (P < .001, P < .001, and P = .004, respectively; alpha = .017) than control rats, and lower MTR, DV, and MTT (P = .014, .001, and .010, respectively; alpha = .017) than cirrhotic rats. Cirrhotic rats had a higher FWR and a lower PF (P < .001, alpha = .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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Contrast Media
  • Discriminant Analysis
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Gadolinium DTPA
  • Image Processing, Computer-Assisted
  • Liver / blood supply
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Prospective Studies
  • Rats
  • Rats, Wistar

Substances

  • Contrast Media
  • gadodiamide
  • Gadolinium DTPA