Assessment of angiogenesis in rabbit orthotropic liver tumors using three-dimensional dynamic contrast-enhanced ultrasound compared with two-dimensional DCE-US

  • Qiao Zheng
  • Jian-chao Zhang
  • Zhu Wang
  • Si-Min Ruan
  • Wei Li
  • Fu-Shun Pan
  • Li-Da Chen
  • Yu-Chen Zhang
  • Wen-Xin Wu
  • Xiao-Yan Xie
  • Ming-De Lu
  • Quan-Yuan ShanEmail author
  • Wei WangEmail author
Original Article



To evaluate quantitative three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) in the assessment of tumor angiogenesis using an orthotropic liver tumor model.


Nine New Zealand white rabbits with liver orthotropic VX2 tumors were established and imaged by two-dimensional (2D) and 3D DCE-US after SonoVue® bolus injections. The intraclass correlation coefficients of perfusion parameters, including peak intensity (PI), mean transit time, time to peak, and area under the curve, were calculated based on time-intensity curve. The percentage area of microvascular (PAMV) and the expression of vascular endothelial growth factor (VEGF) were both evaluated by immunohistochemical analysis and weighted by the tumor activity area ratio. Correlations between quantitative and histologic parameters were analyzed.


The reproducibility of 3D DCE-US quantitative parameters was excellent (ICC 0.91–0.99); but only PI showed high reproducibility (ICC 0.97) in 2D. None of the parameters of quantitative 2D DCE-US were significantly correlated with weighted PAMV or VEGF. For 3D DCE-US, there was a positive correlation between PI and weighted PAMV (r = 0.74, P = 0.04) as well as VEGF (r = 0.79, P = 0.02).


Quantitative parameters of 3D DCE-US show feasibility, higher reproducibility and accuracy for the assessment of tumor angiogenesis using an orthotropic liver tumor model compared with 2D DCE-US.


Ultrasonography Three-dimensional imaging Pathologic neovascularization Assessment 



Arbitrary units


Area under the curve


Dynamic contrast-enhanced ultrasound


Intraclass correlation coefficient


Mean transit time


Percentage area of microvascular


Peak intensity


Region of interest




Time-intensity curve


Time to peak




Vascular endothelial growth factor


Volume of interest



Funding was provided by Natural Science Foundation of China (Grant no. 81601500), Natural Science Foundation of Guangdong Province (Grant nos. 2017A030313661, 2016A030310143), Medical Science and Technology Foundation of Guangdong Province (Grant no. 2017A020215195)

Compliance with ethical standards

Ethical approval

All animal experiments were complied with the ARRIVE guidelines and carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals. All applicable institutional and national guidelines for the care and use of animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11604_2019_861_MOESM1_ESM.doc (82 kb)
Supplementary material (doc 82kb)


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Copyright information

© Japan Radiological Society 2019

Authors and Affiliations

  1. 1.Department of Medical Ultrasonics, Institute of Diagnostic and Interventional UltrasoundThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  3. 3.Department of Hepatobiliary SurgeryThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China

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