Abstract
Abstract Microbubble contrast agents are used to enhance the visualization of the microcirculation in human and mouse tumors. Specifically, contrast agents allow for the relative quantification of tissue perfusion and vascular volume. The in vivo expression of endothelial cell surface markers can also be studied using targeted microbubbles. In this study a nonlinear contrast agent imaging technique, employing amplitude modulation on a linear array-based micro-ultrasound system was used to visualize and quantify time to peak enhancement (TP) and vascular volume (VV) in subcutaneous tumors, as well as to assess expression levels of VEGFR2. A Vevo 2100 high resolution ultrasound imaging system (VisualSonics Inc, Toronto, Canada) was used and all images were acquired with the MS-250 (center operating frequency of 20MHz, axial resolution 75um) probe. Tumor flow was assessed using MicroMarker contrast agents. A bolus delivery was employed to generate time-intensity curves of contrast wash-in; prototype analytical software was used to perform curve fit analysis and to generate parametric images visually depicting VV and TP as an overlay on the anatomical images. Additionally, Target-Ready MicroMarker contrast agents were conjugated to VEGFR2 antibodies to assess the expression level of this endothelial cell surface receptor. Again, prototype analytical software was used to quantify the relative expression of this target and to generate parametric images of its expression pattern within the tumor. All images were acquired from athymic nude mice implanted with hepatocellular carcinoma cells (Hep3B-Luc-C4) subdermally in the hind limb 4 to 5 weeks before imaging. Results showed heterogeneity in TP and VV in all tumors. TP ranged from 3.5 seconds in well perfused regions to 12 seconds in poorly perfused tumor regions. The graphical appearance of the associated parametric images readily revealed these differences. Assessment of VEGFR2 expression completed in 2D and 3D showed 2-3 times enhancement in VEGFR2 binding over that observed with the isotype control antibody. These results are consistent with previous methods using linear contrast processing. Overall this study shows the utility of nonlinear processing of contrast signals in assessment of various flow related parameters of the tumor microcirculation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3985.
Published Version
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