Evaluation of antiangiogenic and antiproliferative effects of sorafenib by sequential histology and intravoxel incoherent motion diffusion-weighted imaging in an orthotopic hepatocellular carcinoma xenograft model

J Magn Reson Imaging. 2017 Jan;45(1):270-280. doi: 10.1002/jmri.25344. Epub 2016 Jun 14.

Abstract

Purpose: To investigate the effectiveness of intravoxel incoherent motion (IVIM) in the assessment of the therapeutic efficacy of sorafenib in an orthotopic hepatocellular carcinoma (HCC) xenograft model.

Materials and methods: Thirty-five HCC nude mouse models were established. IVIM was performed on a 1.5T MR scanner at baseline (n = 5) and serially at 7, 14, and 21 days after sorafenib treatment. The apparent diffusion coefficient (ADCtotal ), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) at these timepoints were measured and compared between the treated (n = 15) and control group (n = 15). Differences in measurements among different timepoints were evaluated. Correlations between IVIM parameters and histologic features including necrotic fraction (NF) and microvessel density (MVD) were analyzed.

Results: Compared to the control group, ADCtotal and D were significantly higher at each timepoint (P = 0.009), while f significantly decreased at 7 days (P = 0.009) and increased at 21 days (P = 0.028) in the treated group. Serial measurements in the treated group showed that both ADCtotal and D increased significantly at 7, 14, and 21 days compared to baseline (P < 0.05), while f significantly declined at 7 days (P = 0.016) and increased at 21 days (P = 0.009). Significant correlations were found between ADCtotal and NF (r = 0.811, P < 0.001), D and NF (r = 0.838, P < 0.001), and between f and NF (r = 0.528, P = 0.017) in the treated group.

Conclusion: IVIM may provide useful biomarkers for evaluating the therapeutic effects of sorafenib on HCC.

Level of evidence: 1 J. Magn. Reson. Imaging 2017;45:270-280.

Keywords: hepatocellular carcinoma; intravoxel incoherent motion; micro-vessel density; necrosis; sorafenib.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diffusion Magnetic Resonance Imaging / methods*
  • Image Enhancement / methods
  • Image Interpretation, Computer-Assisted / methods
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Magnetic Resonance Angiography / methods*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Motion
  • Neovascularization, Pathologic / diagnostic imaging*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sorafenib
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib