Power Doppler ultrasound and contrast-enhanced ultrasound demonstrate non-invasive tumour vascular response to anti-vascular therapy in canine cancer patients
Power Doppler ultrasound and contrast-enhanced ultrasound demonstrate non-invasive tumour vascular response to anti-vascular therapy in canine cancer patients
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DOI：
10.1038/s41598-019-45682-2
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发表时间：
2019-06-25
影响因子：
4.6
通讯作者：
de Rooster, Hilde
中科院分区：
文献类型：
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作者：
Abma, Eline;Stock, Emmelie;de Rooster, Hilde
Combretastatin A4-phosphate（CA 4P）是一种抗血管药物，可选择性地关闭肿瘤的血液供应，导致广泛的肿瘤坏死。本研究的目的是评估在体内，非侵入性超声技术的早期评价肿瘤灌注后，CA 4 P治疗自发性肿瘤。入组了8只携带自发性肿瘤的犬，随后接受单剂量静脉内CA 4P治疗。通过能量多普勒超声（PDUS）预处理（0 h）、注射期间（10 min、20 min、30 min）和CA 4P输注后（24 h和72 h）评价肿瘤灌注。对肿瘤组织的血管指数（VI）进行定量分析，并与微血管密度（MVD）的免疫组化评价结果进行相关性分析。在治疗前和治疗后72 h通过对比增强超声（CEUS）评价中心和外周灌注。治疗后，PDUS显示在CA 4P输注10分钟内VI显著降低。CEUS参数显示肿瘤中心部位血流速度和体积显著降低。组织学检查显示，MVD减少4.4倍（p < 0.001，95% CI [2.2，9.4]），坏死肿瘤组织增加4.1倍（p = 0.003，95% CI [1.4，11.8]）。发现PDUS结果与免疫组化结果之间存在强相关性（Pearson R-2 = 0.957，p < 0.001）。此外，PDUS的发现得到了CEUS分析的客观结果的支持。这些数据表明，超声在实时、无创监测肿瘤血管反应中的作用是CA 4P治疗疗效的早期指标。
Combretastatin A4-phosphate (CA4P) is an anti-vascular agent which selectively shuts down blood supply in tumours, resulting in extensive tumour necrosis. The aim of this study was to assess in vivo, non-invasive ultrasound techniques for the early evaluation of tumour perfusion following CA4P treatment of spontaneous tumours. Eight dogs that bore spontaneous tumours were enrolled and were subsequently treated with a single dose of intravenous CA4P. Perfusion of tumours was evaluated by power Doppler ultrasound (PDUS) pre-treatment (0 h), during the injection (10 min, 20 min, 30 min) and after CA4P infusion (24 and 72 h). Vascularity index (VI) of the tumour tissue was quantitatively analysed and accuracy was verified by correlation analysis with the results of immunohistochemical evaluation of microvessel density (MVD). Central and peripheral perfusion was evaluated by contrast-enhanced ultrasound (CEUS) pre-treatment and at 72 h post-treatment. Post-treatment, PDUS demonstrated a significant decrease in VI within 10 min of CA4P infusion. CEUS parameters demonstrated a significant decrease in blood velocity and volume in the central aspect of the tumour. Histology revealed a 4.4-fold reduction (p < 0.001, 95% CI [2.2,9.4]) in MVD and a 4.1-fold increase (p = 0.003, 95% CI [1.4,11.8]) in necrotic tumour tissue. A strong correlation between PDUS results and immunohistochemical results was found (Pearson R-2 = 0.957, p < 0.001). Furthermore, the findings of PDUS were supported by the objective results of the CEUS analyses. These data suggest a role for ultrasound in real-time, non-invasive monitoring of tumour vascular response as an early indicator of CA4P treatment efficacy.