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Joshua Rychak, Ph.D
Research Interests: Selectively targeted ultrasound contrast agents have many potential applications in preclinical research and clinical diagnosis. Ultrasound contrast agents, also known as microbubbles, can be targeted to desired molecular markers of disease by conjugating a targeting ligand to the microbubble surface. The targeted microbubbles are administered intravenously and, after a short circulation time, achieve adhesion to the targeted vascular endothelium. Adherent microbubbles can be detected using conventional (2-20 MHz) or high-frequency (20-40 MHz) ultrasound imaging. This enables detection of the location and extent of disease at the molecular level. This technique is also used for functional imaging with blood-pool targeted microbubbles. My work is focused upon engineering novel microbubble contrast agents that exhibit enhanced targeted adhesion. Structural modifications to the microbubble shell, mechanical alterations, acoustic radiation force manipulation, and unique targeting ligand strategies are being investigated. The adhesive behavior of targeted microbubbles is examined using several varieties of in vitro flow chamber, and in vivo using intravital microscopy. The targeted microbubbles are subsequently investigated as contrast agents for ultrasound molecular imaging in mouse and rat models of disease. I am currently investigating ultrasound molecular imaging in models of tumor angiogenesis, ischemic injury, and atherosclerosis and other inflammatory diseases. Takalkar, A. M., Klibanov, A. L., Rychak, J. J., Lindner, J. R. & Ley, K. Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J Control Release 96, 473-482 (2004). Rychak, J. J., Lindner, J. R., Ley, K. & Klibanov, A. L. Deformable gas-filled microbubbles targeted to P-selectin. J Control Release 114, 288-299 (2006). Rychak, J. J. et al. Selectin ligands promote ultrasound contrast agent adhesion under shear flow. Mol Pharm 3, 516-524 (2006). Rychak, J. J., Klibanov, A. L. & Hossack, J. A. Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification. IEEE Trans Ultrason Ferroelectr Freq Control 52, 421-433 (2005). Klibanov, A. L. et al. Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow. Contrast Media Mol Imaging 1, 259-266 (2006). |
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