Abstract
The purpose of this study was to compare 4 contrast-enhanced ultrasound (US) techniques for measuring tumor neovascularity to 4 markers of angiogenesis in 2 xenograft rat models. Glioma (C6; 75 rats) or breast cancer (NMU; 72 rats) cells were implanted in 147 rats. The US contrast agent Optison (GE Healthcare, Princeton, NJ) was injected in a tail vein (dose: 0.4 ml/kg). Power Doppler imaging (PDI), pulse-subtraction harmonic imaging (PSHI), flash-echo imaging (FEI) and Microflow imaging (MFI) was performed with an Aplio scanner (Toshiba America Medical Systems, Tustin, CA) and a 7.5 MHz linear array. Digital US clips of the tumors were used with image-processing software to calculate fractional tumor neovascularity as contrast enhanced pixels over tumor area (for US) and staining over tumor area (for specimens). Results were compared using linear regression analysis and Z-tests. The tortuous morphology of tumor neovessels (i.e., irregular vessel sizes and distribution) was visualized better with MFI than with the other US modes. The strongest correlation found by linear regression in the C6 model was between PSHI and percent area stained with CD31 (r = 0.37, p 0.22, p 0.15). In conclusion, quantitative contrast-enhanced US measures of tumor neovascularity in the glioma and breast cancer xenograft models C6 and NMU appear to provide a noninvasive marker for angiogenesis
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