ACT 1: PROJ 2: TARGETED HIGH-FREQUENCY ULTRASOUND-CONTRAST AGENT IMAGING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease is the leading cause of death in the United States and it is particularly acute in the state of Hawaii. An urgent need exists for the development of diagnostic imaging methods capable of revealing the associated biological processes involved at the molecular and cellular levels of blood vessels. Targeted ultrasound contrast agents add molecular imaging capabilities to diagnostic ultrasound. The unique advantages of ultrasound in terms of robustness, portability and relative low cost are thus incorporated into techniques to foster rapid translation. Ultrasound contrast agents are encapsulated micro-bubbles which oscillate nonlinearly about their equilibrium radius when acoustically excited. The agents produce unique scattering signatures which foster novel imaging methods that allow for the scattering signatures of blood to be distinguished from that of the surrounding tissue for freely circulating agents. A recent development has been contrast agents, which have specific ligands attached on their shell allowing binding at specific targeted sites. Though still in the early stages of development, targeted ultrasound contrast agents offer great potential for improved molecular imaging capabilities for diagnostic ultrasound. The specific aims of this study are to: 1) experimentally and theoretically characterize individual and groups of targeted agents near vascular walls and under physiological flow conditions from their scattering signatures for high frequency ultrasound and develop robust detection methods; and 2) investigate methods for image-guided assessment of leukocyte dysfunction for high frequencies. An understanding of how the close proximity of cell layers and likewise vessel walls change an ultrasound contract agents dynamics and scattering signature will provide the foundation for detection methods that can discriminate between bound and unbound agents.