使用临床矩阵阵列超声换能器对结肠癌血管生成进行三维超声分子成像。
Three-dimensional ultrasound molecular imaging of angiogenesis in colon cancer using a clinical matrix array ultrasound transducer.
作者信息
Wang Huaijun, Kaneko Osamu F, Tian Lu, Hristov Dimitre, Willmann Jürgen K
机构信息
From the Departments of *Radiology, Molecular Imaging Program at Stanford, School of Medicine, †Health, Research and Policy, and ‡Radiation Oncology, Stanford University, Stanford, CA.
出版信息
Invest Radiol. 2015 May;50(5):322-9. doi: 10.1097/RLI.0000000000000128.
OBJECTIVES
We sought to assess the feasibility and reproducibility of 3-dimensional ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression in tumor angiogenesis using a clinical matrix array transducer and a clinical grade VEGFR2-targeted contrast agent in a murine model of human colon cancer.
MATERIALS AND METHODS
Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice with human colon cancer xenografts (n = 33) were imaged with a clinical ultrasound system and transducer (Philips iU22; X6-1) after intravenous injection of either clinical grade VEGFR2-targeted microbubbles or nontargeted control microbubbles. Nineteen mice were scanned twice to assess imaging reproducibility. Fourteen mice were scanned both before and 24 hours after treatment with either bevacizumab (n = 7) or saline only (n = 7). Three-dimensional USMI data sets were retrospectively reconstructed into multiple consecutive 1-mm-thick USMI data sets to simulate 2-dimensional imaging. Vascular VEGFR2 expression was assessed ex vivo using immunofluorescence.
RESULTS
Three-dimensional USMI was highly reproducible using both VEGFR2-targeted microbubbles and nontargeted control microbubbles (intraclass correlation coefficient, 0.83). The VEGFR2-targeted USMI signal significantly (P = 0.02) decreased by 57% after antiangiogenic treatment compared with the control group, which correlated well with ex vivo VEGFR2 expression on immunofluorescence (ρ = 0.93, P = 0.003). If only central 1-mm tumor planes were analyzed to assess antiangiogenic treatment response, the USMI signal change was significantly (P = 0.006) overestimated by an average of 27% (range, 2%-73%) compared with 3-dimensional USMI.
CONCLUSIONS
Three-dimensional USMI is feasible and highly reproducible and allows accurate assessment and monitoring of VEGFR2 expression in tumor angiogenesis in a murine model of human colon cancer.
目的
我们试图使用临床矩阵阵列换能器和临床级血管内皮生长因子受体2（VEGFR2）靶向造影剂，在人结肠癌小鼠模型中评估三维超声分子成像（USMI）检测肿瘤血管生成中VEGFR2表达的可行性和可重复性。
材料与方法
动物研究经机构实验动物护理管理小组批准。将人结肠癌异种移植小鼠（n = 33）静脉注射临床级VEGFR2靶向微泡或非靶向对照微泡后，用临床超声系统和换能器（飞利浦iU22；X6 - 1）进行成像。19只小鼠进行了两次扫描以评估成像的可重复性。14只小鼠在使用贝伐单抗（n = 7）或仅用生理盐水（n = 7）治疗前和治疗后24小时进行扫描。三维USMI数据集被回顾性重建为多个连续的1毫米厚的USMI数据集，以模拟二维成像。使用免疫荧光在体外评估血管VEGFR2表达。
结果
使用VEGFR2靶向微泡和非靶向对照微泡时，三维USMI具有高度可重复性（组内相关系数，0.83）。与对照组相比，抗血管生成治疗后，VEGFR2靶向USMI信号显著（P = 0.02）降低了57%，这与免疫荧光体外VEGFR2表达密切相关（ρ = 0.93，P = 0.003）。如果仅分析中央1毫米肿瘤平面来评估抗血管生成治疗反应，与三维USMI相比，USMI信号变化被显著（P = 0.006）高估，平均高估27%（范围，2% - 73%）。
结论
三维USMI是可行的且具有高度可重复性，能够准确评估和监测人结肠癌小鼠模型中肿瘤血管生成中的VEGFR2表达。
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