Correlations between quantitative parameters of contrast-enhanced ultrasound and vasculogenic mimicry in murine tumor model: a novel noninvasive technique for assessment?

Yue-tao Zhou†View ORCID ID profile,
Wei-wei Cai†,
Yue Li†,
Xiao Jiang,
Lei Feng,
Qiao-ying Zhu,
Yan-ling Liu,
Yu-xiao Chen,
Shuang-shuang Li,
Bin Du,
Florian Lang,
Peng-xi WuEmail author and
Li-ying QiuEmail author

†Contributed equally

Biological Procedures Online201921:11

https://doi.org/10.1186/s12575-019-0101-5

Received: 1 April 2019
Accepted: 21 May 2019
Published: 11 June 2019

Abstract

Objective

Vasculogenic mimicry (VM) is a novel mechanism of tumor blood supply distinct from endothelial vessel (EV). VM is associated with malignancy, invasion, metastasis, and poor prognosis. Hitherto a noninvasive method for the assessment of VM in vivo has been lacking.

Methods

Contrast-enhanced ultrasound (CEUS) was performed to evaluate the quantitative parameters of tumors in mice. CD31 immunohistochemistry-Periodic Acid-Schiff double staining was conducted to identify the VM or EV in tumor tissues. Correlations between perfusion parameters and VM density was analyzed by Pearson correlation test.

Results

By the 15th day after tumor inoculation, the EV and VM density was 31.15 ± 7.14 and 14.11 ± 2.99 per 200× field. The maximal intensity (IMAX) was 301.19 ± 191.56%, and the rise time (RT), time to peak (TTP) and mean transit time (mTT) were 17.38 ± 7.82 s, 20.27 ± 9.61 s and 58.09 ± 26.44 s, respectively. VM density positively correlated to RT (r = 0.3598, P = 0.0226), TTP (r = 0.3733, P = 0.0177) and mTT(r = 0.6483, P < 0.0001), whereas EV density positively correlated to IMAX (r = 0.4519, P = 0.0034). The vascular diameter of VM was substantially larger than that of EV (43.81 ± 5.88 μm vs 11.21 ± 4.13 μm).

Conclusion

Three quantitative parameters related to VM were obtained and the relationships between CEUS and VM were established. CEUS might thus provide a novel noninvasive method to assess VM in vivo.