Development and preliminary testing of a translational model of hepatocellular carcinoma for MR imaging and interventional oncologic investigations

J Vasc Interv Radiol. 2012 Mar;23(3):385-95. doi: 10.1016/j.jvir.2011.11.018. Epub 2012 Jan 20.

Abstract

Purpose: To develop a translational rat hepatocellular carcinoma (HCC) disease model for magnetic resonance (MR) imaging and image-guided interventional oncologic investigations.

Materials and methods: Male rats underwent sham control surgery (n = 6), selective bile duct ligation (SBDL; n = 4), or common bile duct ligation (CBDL; n = 6), with procedure optimization in four rats and N1S1 hepatoma cell injection into two or three sites in the livers of 12 rats. All rats subsequently underwent MR imaging to assess tumor establishment and volume. Mesenteric angiography and percutaneous MR-guided laser ablation of the liver were performed in a subgroup of animals (n = 4). Animal weight and liver test results were monitored. After harvesting, the livers were subjected to gross and microscopic analysis. Tumor volume and laboratory parameters were assessed between ligation groups.

Results: MR imaging demonstrated hyperintense T2 and hypointense T1 lesions with tumor induction in five of 10 (50.0%), seven of eight (87.5%), and 12 of 12 (100%) sites in the control, SBDL, and CBDL groups, respectively. Tumor volumes differed significantly by group (P < .02). Mesenteric angiography demonstrated an enhancing tumor stain. Clinical and laboratory assessment revealed a significant decrease in weight (P = .01) and albumin level (P < .01) and an increase in total bilirubin level (P = .02) in CBDL rats but not SBDL rats (P = 1.0). Histologic examination showed high-grade HCCs with local and vascular invasion within the context of early fibrosis in CBDL and SBDL rats. MR-guided laser ablation generated a 1-2-cm ablation zone with histologic findings consistent with reversible and irreversible injury.

Conclusions: A biologically relevant rat HCC disease model has been developed for MR imaging and preliminary interventional oncologic applications.

Publication types

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

MeSH terms

  • Animals
  • Aortography
  • Bile Ducts / surgery
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery*
  • Cell Line, Tumor
  • Laser Therapy*
  • Ligation
  • Liver Cirrhosis / pathology
  • Liver Neoplasms, Experimental / diagnostic imaging
  • Liver Neoplasms, Experimental / etiology
  • Liver Neoplasms, Experimental / pathology*
  • Liver Neoplasms, Experimental / surgery*
  • Magnetic Resonance Imaging*
  • Magnetic Resonance Imaging, Interventional*
  • Male
  • Neoplasm Invasiveness
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Translational Research, Biomedical*
  • Tumor Burden