Assessment of Molecular Acoustic Angiography for C

Authors: Brooks D Lindsey Sarah E Shelton F Stuart Foster Paul A Dayton

Publish Date: 2016/08/12

Volume: 19, Issue: 2, Pages: 194-202

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Abstract

The purposes of the present study is to evaluate a new ultrasound molecular imaging approach in its ability to image a preclinical tumor model and to investigate the capacity to visualize and quantify coregistered microvascular and molecular imaging volumesMolecular imaging using the new technique was compared with a conventional ultrasound molecular imaging technique multipulse imaging by varying the injected microbubble dose and scanning each animal using both techniques Each of the 14 animals was randomly assigned one of three doses bolus dose was varied and the animals were imaged for three consecutive days so that each animal received every dose A microvascular scan was also acquired for each animal by administering an infusion of nontargeted microbubbles These scans were paired with coregistered molecular images VEGFR2targeted microbubbles the vessels were segmented and the spatial relationships between vessels and VEGFR2 targeting locations were analyzed In five animals an additional scan was performed in which the animal received a bolus of microbubbles targeted to E and Pselectins Vessel tortuosity as a function of distance from VEGF and selectin targeting was analyzed in these animalsAlthough resulting differences in image intensity due to varying microbubble dose were not significant between the two lowest doses superharmonic imaging had significantly higher contrasttotissue ratio CTR than multipulse imaging mean across all doses 1398 dB for molecular acoustic angiography vs 053 dB for multipulse imaging p = 49 × 10−10 Analysis of registered microvascular and molecular imaging volumes indicated that vessel tortuosity decreases with increasing distance from both VEGFR2 and selectintargeting sitesMolecular acoustic angiography superharmonic molecular imaging exhibited a significant increase in CTR at all doses tested due to superior rejection of tissue artifact signals Due to the high resolution of acoustic angiography molecular imaging it is possible to analyze spatial relationships in aligned microvascular and molecular superharmonic imaging volumes Future studies are required to separate the effects of biomarker expression and blood flow kinetics in comparing local tortuosity differences between different endothelial markers such as VEGFR2 Eselectin and PselectinThis work was supported by grants R01CA170665 R01CA189479 U01CA189281 F32EB018715 and T32HL069768 from the National Institutes of Health We thank Mike Lee and Emmanuel Cherin for their contributions to the design and fabrication of prototype transducers Animal studies were performed within the Lineberger Comprehensive Cancer Center LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant CA16086 to the UNC Lineberger Comprehensive Cancer CenterF Stuart Foster is a consultant and receives research funding from VisualSonics Inc F Stuart Foster and Paul A Dayton are inventors on a pending patent describing the acoustic angiography technology Paul A Dayton is a cofounder of SonoVol Inc a company which has licensed the patent enabling acoustic angiography and also was formerly on the scientific advisory board for Targeson LLC The authors declare that they have no conflict of interests with any other companies listed in this paper

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