? Recently, the development of targeted contrast agents for molecular imaging has caught the attention of the medical and scientific community. Targeted ultrasound contrast agents, microbubbles which bear adhesion ligands to specific molecular targets expressed in areas such as angiogenesis, inflammation, or thrombus have the potential to make a significant impact in the detection, assessment, and localization of pathologies otherwise undetectable with medical imaging. Because of the convenience and availability of ultrasound as an imaging technology, targeted contrast agents for use with ultrasound have the potential to rapidly transform this modality into an even more powerful clinical tool. Unfortunately, recent studies with targeted ultrasound contrast agents have failed to illustrate the sensitivity hoped for to make this technique revolutionary. In this proposal, we present a plan to increase the sensitivity of ultrasound to targeted contrast agents over an order of magnitude. Our model target for these studies is angiogenesis (the formation of new blood vessels), which is required for tumor growth beyond 1-2 mm in diameter. The integrin alpha(v)beta(3) is over-expressed in regions of angiogenesis, and has been shown to correlate with tumor grade. These properties make the alpha (v)beta(3) integrin an ideal target for site-directed contrast agents. This proposal describes a three-part method to achieve the desired substantial increase in sensitivity by combining a completely new contrast agent with a novel contrast agent delivery technique, and we package these improvements with the substantially improved detection strategies only possible due to the improvements in the agent and the delivery. The combined tools and experience of the Departments of Biomedical and Chemical Engineering, the School of Veterinary Medicine, and the Cancer Center at the University of California, Davis, provide a unique and qualified research group for implementing this new system for molecular imaging with ultrasound. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21EB005325-04
Application #
7547141
Study Section
Special Emphasis Panel (ZEB1-OSR-C (M1))
Program Officer
Lopez, Hector
Project Start
2005-09-15
Project End
2009-08-31
Budget Start
2007-12-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$348,695
Indirect Cost
Name
North Carolina State University Raleigh
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Chitnis, P V; Lee, P; Dayton, P A et al. (2011) Characterisation of polymer shelled microbubbles in wall less flow phantom using high frequency ultrasound and video microscopy. Bubble Sci Eng Technol 3:73-78
Streeter, Jason E; Gessner, Ryan C; Tsuruta, James et al. (2011) Assessment of molecular imaging of angiogenesis with three-dimensional ultrasonography. Mol Imaging 10:460-8
Mullin, Lee; Gessner, Ryan; Kwan, James et al. (2011) Effect of anesthesia carrier gas on in vivo circulation times of ultrasound microbubble contrast agents in rats. Contrast Media Mol Imaging 6:126-31
Streeter, Jason E; Gessner, Ryan; Miles, Iman et al. (2010) Improving sensitivity in ultrasound molecular imaging by tailoring contrast agent size distribution: in vivo studies. Mol Imaging 9:87-95
Gessner, Ryan; Dayton, Paul A (2010) Advances in molecular imaging with ultrasound. Mol Imaging 9:117-27
Gessner, Ryan; Lukacs, Marc; Lee, Mike et al. (2010) High-resolution, high-contrast ultrasound imaging using a prototype dual-frequency transducer: in vitro and in vivo studies. IEEE Trans Ultrason Ferroelectr Freq Control 57:1772-81
Kaya, Mehmet; Feingold, Steven; Hettiarachchi, Kanaka et al. (2010) Acoustic responses of monodisperse lipid-encapsulated microbubble contrast agents produced by flow focusing. Bubble Sci Eng Technol 2:33-40
Kogan, Paul; Gessner, Ryan C; Dayton, Paul A (2010) Microbubbles in Imaging: Applications Beyond Ultrasound. Bubble Sci Eng Technol 2:3-8
Feingold, Steven; Gessner, Ryan; Guracar, Ismayil M et al. (2010) Quantitative volumetric perfusion mapping of the microvasculature using contrast ultrasound. Invest Radiol 45:669-74
Kaya, Mehmet; Gregory 5th, Thomas S; Dayton, Paul A (2009) Changes in lipid-encapsulated microbubble population during continuous infusion and methods to maintain consistency. Ultrasound Med Biol 35:1748-55

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