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 a leading cause of morbidity and mortality in Hawaii and the United States. Upon closer examination of cardiovascular disease death rates in Hawaii, Filipinos and Native Hawaiians have disproportionally higher mortality rates than the general population. Moreover, cardiovascular disease is responsible for a significant portion of the state health care costs from hospitalizations. Sudden cardiac death and acute heart attack often occur without warning and these complications are typically associated with a plaque rupture corresponding to advanced stages of coronary atherosclerotic heart disease. Recommendations in terms of diet and exercise have been developed to prevent atherosclerotic cardiovascular disease, but less effort has been made to aid patients who may be at risk for vulnerable plaque rupture. Coronary angiography has limitations because it does not allow for inspection of the vessel wall and can only determine narrowing of the vessel lumen. Intravascular ultrasound (IVUS) provides a two-dimensional cross-sectional view of the arterial wall and offers some ability to determine lumen and vessel areas. However, severe limitations exist in the classification of plaques. The high frequency signal may be confused with acoustic shadowing aspects. The mechanisms of plaque rupture are not well understood and no imaging modality currently exists which can robustly detect vulnerable plaques. Vulnerable plaques are characterized by a large lipid core with a thin and inflamed fibrous cap. Low endothelial shear stress from the surrounding blood flow can serve as stimulus for the progression and differentiation of an early fibroatheroma to a high-risk plaque. It has been hypothesized that the vasa vasorum, which supplies nutrients to the adventia, may serve as a conduit for white blood cells to migrate into the lining of the vessel wall. Subsequently, expansive vascular remodeling can occur within these plaques. The addition of molecular-imaging capabilities to IVUS probes would provide an improvement in detecting biomarkers for plaque rupture, such as neovascularization and inflammation. Targeted ultrasound contrast agents are encapsulated microbubbles with attached ligands that allow them to bind to specific diseased sites. The center frequency of IVUS probes (35-50 MHz) is much higher than conventional diagnostic ultrasound systems. We are investigating the targeting efficacy in physiological flow conditions for large vessels and the optimal acoustical response of targeted agents at high frequency.