Abstract
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.
Highlights
Renca cells readily formed spheroidal tumors when inoculated into the chorioallantoic membrane (CAM) of chicken embryos, as demonstrated in Fig. 1A, with the majority of the tumor mass growing below the surface of the membrane
All of the engrafted embryos demonstrated visible tumor masses for the first day of therapy occurring on embryonic development day 11 (EDD-11), indicating high engraftment efficiency of this cell line on the CAM
The dimethyl sulfoxide (DMSO 1%) vehicle control group and pazopanib treated cohorts had 6/8 and 5/8 embryos survive until ultrasound imaging on EDD-17, respectively
Summary
The proposed UMI method based on SVD clutter filtering was applied to high frequency ultrasound data acquired with standard ultrasound imaging settings (see Fig. 2 and Methods section for details). Rich vascular architectures and blood flow signal in microvessels could be visualized for both control and treated tumor groups, as depicted in second column of Fig. 3 (3D images are provided in Supplementary Fig. S1 and Videos S1–S4).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
