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

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Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Objectives

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

Methods

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.

Results

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).

Conclusion

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.

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Abbreviations

au:

Arbitrary units

AUC:

Area under the curve

DCE-US:

Dynamic contrast-enhanced ultrasound

ICC:

Intraclass correlation coefficient

MTT:

Mean transit time

PAMV:

Percentage area of microvascular

PI:

Peak intensity

ROI:

Region of interest

3D:

Three-dimensional

TIC:

Time-intensity curve

TTP:

Time to peak

2D:

Two-dimensional

VEGF:

Vascular endothelial growth factor

VOI:

Volume of interest

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Funding

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)

Author information

Author notes

  1. Qiao Zheng and Jian-chao Zhang contributed equally to this study.

Authors and Affiliations

  1. Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China

    Qiao Zheng, Jian-chao Zhang, Zhu Wang, Si-Min Ruan, Wei Li, Fu-Shun Pan, Li-Da Chen, Xiao-Yan Xie, Ming-De Lu, Quan-Yuan Shan & Wei Wang

  2. Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China

    Yu-Chen Zhang & Wen-Xin Wu

  3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China

    Ming-De Lu

Authors
  1. Qiao Zheng
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  2. Jian-chao Zhang
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Corresponding authors

Correspondence to Quan-Yuan Shan or Wei Wang.

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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.

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Cite this article

Zheng, Q., Zhang, Jc., Wang, Z. et al. Assessment of angiogenesis in rabbit orthotropic liver tumors using three-dimensional dynamic contrast-enhanced ultrasound compared with two-dimensional DCE-US. Jpn J Radiol 37, 701–709 (2019). https://doi.org/10.1007/s11604-019-00861-z

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  • DOI: https://doi.org/10.1007/s11604-019-00861-z

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