Noninvasive Contrast-Free 3D Evaluation of Tumor Angiogenesis with Ultrasensitive Ultrasound Microvessel Imaging
Noninvasive Contrast-Free 3D Evaluation of Tumor Angiogenesis with Ultrasensitive Ultrasound Microvessel Imaging
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DOI：
10.1038/s41598-019-41373-0
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发表时间：
2019-03-20
影响因子：
4.6
通讯作者：
Chen, Shigao
中科院分区：
文献类型：
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作者：
Huang, Chengwu;Lowerison, Matthew R.;Chen, Shigao
超声微血管成像（UMI）在应用超快平面波采集时，已证明与常规多普勒成像相比具有上级血液信号灵敏度。在这里，我们提出了一种高空间分辨率和超灵敏的UMI，它是基于传统的逐行高频超声成像仪和奇异值分解（SVD）杂波滤波的可视化和量化的肿瘤微血管和灌注。该技术应用于肾细胞癌的鸡胚肿瘤模型，该模型用两种FDA批准的抗血管生成剂以临床相关剂量治疗。我们证明了UMI三维评估的可行性，以实现高灵敏度的微血管检测，使用传统的逐线超声成像的临床前和市售的高频超声设备，无需软件或硬件修改。与常规能量多普勒成像相比，使用组织学分析和免疫组织化学作为参考标准，来自UMI图像的定量参数（血管化指数和分数运动血容量）提供了显著改善的抗血管生成治疗反应评价。这项概念验证研究表明，高频UMI是一种低成本、无造影剂、易于应用、可获得的定量成像工具，可用于肿瘤表征，这可能对临床前评价和抗癌治疗的纵向监测非常有用。
Ultrasound microvessel imaging (UMI), when applied with ultrafast planewave acquisitions, has demonstrated superior blood signal sensitivity in comparison to conventional Doppler imaging. Here we propose a high spatial resolution and ultra-sensitive UMI that is based on conventional line-by-line high-frequency ultrasound imagers and singular value decomposition (SVD) clutter filtering for the visualization and quantification of tumor microvasculature and perfusion. The technique was applied to a chicken embryo tumor model of renal cell carcinoma that was treated with two FDA-approved anti-angiogenic agents at clinically relevant dosages. We demonstrate the feasibility of 3D evaluation with UMI to achieve highly sensitive detection of microvasculature using conventional line-by-line ultrasound imaging on a preclinical and commercially available high-frequency ultrasound device without software or hardware modifications. Quantitative parameters (vascularization index and fractional moving blood volume) derived from UMI images provide significantly improved evaluation of anti-angiogenic therapy response as compared with conventional power Doppler imaging, using histological analysis and immunohistochemistry as the reference standard. This proof-of-concept study demonstrates that high-frequency UMI is a low-cost, contrast-agent-free, easily applicable, accessible, and quantitative imaging tool for tumor characterization, which may be very useful for preclinical evaluation and longitudinal monitoring of anti-cancer treatment.