Many promising studies indicate that molecular imaging with ultrasound can rapidly and economically provide sensitive, high-resolution detection of vascular events, such as angiogenesis, inflammation and thrombus. Thus, Ultrasound molecular imaging has the potential to have a widespread impact in clinical medicine and biological research. Current non-contrast-assisted ultrasound lacks the specificity to detect molecular signatures of targeted disease events, such as angiogenesis. However, ultrasound has the advantages of low cost, portability, and dynamic imaging capability, and is already widely used for clinical diagnosis. Targeted contrast agents have been developed for ultrasound molecular imaging, but their immunogenic properties make them untranslatable to the clinic. Thus, improving the safety and enhancing the sensitivity of ultrasound molecular imaging will have a significant impact on the diagnosis and assessment of thrombus, inflammation, and cancer. Before ultrasound molecular imaging can be translated to the clinic, the immunogenic effects caused by the exposure of targeting ligands on the contrast agent surface must be reduced. We propose research studies to examine in detail the physicochemical mechanisms of immune response to ultrasound contrast agents, and we will use this data to design contrast agents which are shielded from this immune response. Simultaneously, we will study the ultrasound interaction with stealth agents that have been shown in preliminary data to be selectively activated by ultrasound radiation force. Collaboration with an ultrasound device manufacturer will allow the modification of a small-animal imaging system for specific optimization to work with the new stealth contrast agents for enhanced pre-clinical imaging. The end goal will be to develop safer ultrasound contrast agents which will also exhibit increased specificity and circulation time in-vivo, and to improve ultrasound scanner technology to take advantage of new, stealth contrast agents.

Public Health Relevance

Ultrasound molecular imaging has the potential to have a widespread impact in clinical medicine and biological research. Before ultrasound molecular imaging can be translated to the clinic, the immunogenic effects caused by the exposure of targeting ligands on the contrast agent surface must be reduced. The project will develop safer targeted ultrasound contrast agents with decreased immunogenicity and increased specificity in vivo and improve ultrasound scanner technology to take advantage of the new contrast agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB009066-05
Application #
8094328
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Lopez, Hector
Project Start
2008-09-30
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$273,721
Indirect Cost
Name
University of Colorado at Boulder
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Tsuruta, James K; Klauber-DeMore, Nancy; Streeter, Jason et al. (2014) Ultrasound molecular imaging of secreted frizzled related protein-2 expression in murine angiosarcoma. PLoS One 9:e86642
Dayton, Paul A; Gessner, Ryan C; Phillips, Linsey et al. (2014) The implementation of acoustic angiography for microvascular and angiogenesis imaging. Conf Proc IEEE Eng Med Biol Soc 2014:4283-5
Garg, Sumit; Thomas, Alex A; Borden, Mark A (2013) The effect of lipid monolayer in-plane rigidity on in vivo microbubble circulation persistence. Biomaterials 34:6862-70
Martin, K Heath; Dayton, Paul A (2013) Current status and prospects for microbubbles in ultrasound theranostics. Wiley Interdiscip Rev Nanomed Nanobiotechnol 5:329-45
Streeter, J E; Herrera-Loeza, S G; Neel, N F et al. (2013) A comparative evaluation of ultrasound molecular imaging, perfusion imaging, and volume measurements in evaluating response to therapy in patient-derived xenografts. Technol Cancer Res Treat 12:311-21
Borden, Mark A; Streeter, Jason E; Sirsi, Shashank R et al. (2013) In vivo demonstration of cancer molecular imaging with ultrasound radiation force and buried-ligand microbubbles. Mol Imaging 12:357-63
Streeter, Jason E; Dayton, Paul A (2013) An in vivo evaluation of the effect of repeated administration and clearance of targeted contrast agents on molecular imaging signal enhancement. Theranostics 3:93-8
Gessner, Ryan C; Frederick, C Brandon; Foster, F Stuart et al. (2013) Acoustic angiography: a new imaging modality for assessing microvasculature architecture. Int J Biomed Imaging 2013:936593
Sheeran, Paul S; Streeter, Jason E; Mullin, Lee B et al. (2013) Toward ultrasound molecular imaging with phase-change contrast agents: an in vitro proof of principle. Ultrasound Med Biol 39:893-902
Sheeran, Paul S; Matsunaga, Terry O; Dayton, Paul A (2013) Phase-transition thresholds and vaporization phenomena for ultrasound phase-change nanoemulsions assessed via high-speed optical microscopy. Phys Med Biol 58:4513-34

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