Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma

Magn Reson Imaging. 2019 Apr:57:156-164. doi: 10.1016/j.mri.2018.11.012. Epub 2018 Nov 19.

Abstract

Objectives: To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC).

Methods: Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively.

Results: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min-1, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI Ktrans with histopathologic tissue necrosis (r = -0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05).

Conclusions: Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.

Keywords: Contrast-enhanced functional imaging; Hepatocellular carcinoma; Sorafenib; Tissue perfusion; Vascular permeability.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Capillary Permeability
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Contrast Media / chemistry*
  • Disease Models, Animal
  • Hypoxia
  • Image Processing, Computer-Assisted
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / pathology
  • Magnetic Resonance Imaging*
  • Male
  • Necrosis
  • Neovascularization, Pathologic
  • Permeability
  • Rats
  • Sorafenib / chemistry*

Substances

  • Biomarkers, Tumor
  • Contrast Media
  • Sorafenib