Molecular MR imaging of liver fibrosis: a feasibility study using rat and mouse models

J Hepatol. 2012 Sep;57(3):549-55. doi: 10.1016/j.jhep.2012.04.035. Epub 2012 May 24.


Background & aims: Liver biopsy, the current clinical gold standard for fibrosis assessment, is invasive and has sampling errors, and is not optimal for screening, monitoring, or clinical decision-making. Fibrosis is characterized by excessive accumulation of extracellular matrix proteins including type I collagen. We hypothesize that molecular magnetic resonance imaging (MRI) with a probe targeted to type I collagen could provide a direct and non-invasive method of fibrosis assessment.

Methods: Liver fibrosis was induced in rats with diethylnitrosamine and in mice with carbon tetrachloride. Animals were imaged prior to and immediately following i.v. administration of either collagen-targeted probe EP-3533 or non-targeted control Gd-DTPA. Magnetic resonance (MR) signal washout characteristics were evaluated from T1 maps and T1-weighted images. Liver tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline.

Results: EP-3533-enhanced MR showed greater signal intensity on delayed imaging (normalized signal enhancement mice: control=0.39 ± 0.04, fibrotic=0.55 ± 0.03, p<0.01) and slower signal washout in the fibrotic liver compared to controls (liver t(1/2)=51.3 ± 3.6 vs. 42.0 ± 2.5 min, p<0.05 and 54.5 ± 1.9 vs. 44.1 ± 2.9 min, p<0.01 for fibrotic vs. controls in rat and mouse models, respectively). Gd-DTPA-enhanced MR could not distinguish fibrotic from control animals. EP-3533 gadolinium concentration in the liver showed strong positive correlations with hydroxyproline levels (r=0.74 (rats), r=0.77 (mice)) and with Ishak scoring (r=0.84 (rats), r=0.79 (mice)).

Conclusions: Molecular MRI of liver fibrosis with a collagen-specific probe identifies fibrotic tissue in two rodent models of disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride
  • Collagen Type I / analysis*
  • Contrast Media / analysis
  • Diethylnitrosamine
  • Disease Models, Animal
  • Gadolinium / analysis
  • Half-Life
  • Hydroxyproline / analysis
  • Liver / chemistry
  • Liver / pathology*
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / pathology*
  • Magnetic Resonance Imaging*
  • Male
  • Mice
  • Molecular Imaging*
  • Molecular Probes / analysis
  • Rats
  • Rats, Wistar


  • Collagen Type I
  • Contrast Media
  • Molecular Probes
  • Diethylnitrosamine
  • Gadolinium
  • Carbon Tetrachloride
  • Hydroxyproline