title: Induced hepatic fibrosis in rats: hepatic steatosis, macromolecule content, perfusion parameters, and their correlations--preliminary MR imaging in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Magnetization transfer contrast is not a specific indicator of increased fibrosis in diseased liver; steatosis may influence some perfusion parameters.
authors.affiliation: Department of Diagnostic Radiology, Section of Comparative Medicine, Yale University, New Haven, Conn, USA. hyeonjin.kim@yale.edu
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Kim
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Pinus
authors.forename: Pengyu
authors.initials: P
authors.lastname: Chen
authors.forename: Andrew
authors.initials: A
authors.lastname: Lee
authors.forename: Maolin
authors.initials: M
authors.lastname: Qiu
authors.forename: Mark
authors.initials: M
authors.lastname: Whitlock
authors.forename: Philip S
authors.initials: PS
authors.lastname: Murphy
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
mesh_terms: D000465:Algorithms; D000818:Animals; D003287:Contrast Media; D016002:Discriminant Analysis; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D019786:Gadolinium DTPA; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000098:blood supply; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; C064925:gadodiamide; D019786:Gadolinium DTPA