Three-dimensional ultrasound molecular imaging of angiogenesis in colon cancer using a clinical matrix array ultrasound transducer

• Published in: Investigative radiology Vol. 50; no. 5; p. 322
• Main Authors: Wang, Huaijun, Kaneko, Osamu F, Tian, Lu, Hristov, Dimitre, Willmann, Jürgen K
• Format: Journal Article
• Language: English
• Published: United States 01.05.2015
• Subjects: Animals; Biomarkers - metabolism; Cell Line, Tumor; Colonic Neoplasms - complications; Colonic Neoplasms - diagnostic imaging; Colonic Neoplasms - metabolism; Feasibility Studies; Female; Humans; Image Interpretation, Computer-Assisted - instrumentation; Image Interpretation, Computer-Assisted - methods; Imaging, Three-Dimensional - instrumentation; Imaging, Three-Dimensional - methods; Mice; Mice, Nude; Molecular Imaging - instrumentation; Molecular Imaging - methods; Neovascularization, Pathologic - complications; Neovascularization, Pathologic - diagnostic imaging; Neovascularization, Pathologic - metabolism; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography - instrumentation; Ultrasonography - methods; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 1536-0210
• DOI: 10.1097/RLI.0000000000000128

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. 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. 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. 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.