Traditional means to identify the physiological severity of arterial stenoses are hampered by their inability to identify atheroma extent and composition. New techniques that identify atheroma characterization have not been forthcoming. Acoustic methodologies have shown great promise for atheroma characterization but are hampered by the heterogeneous nature of the disease process. Novel acoustic targeting and highlighting agents such as liposomes may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. The investigators have developed a unique methodology that by process and composition provides these liposomes acoustic characteristics without requiring the addition of entrapped gas. The formulation allows modification for antibody conjugation. Preliminary work has demonstrated that antibody conjugated liposomes can highlight thrombus and atheroma in-vitro and in-vivo. This proposal describes a series of experiments that extend the preliminary work. The researchers will expand upon their previous techniques of liposomal development to optimize formulation. They will develop new techniques of transvascular three-dimensional ultrasonic reconstruction and image characterization techniques that will allow optimal characterization and quantitation of atheroma/atheroma component enhancement using liposomal formulation. They will perform preliminary experiments to determine the ability of these acoustic enhancement agents to provide targeted drug delivery to atheroma. Upon completion, this project will provide a comprehensive methodology for specific atheroma characterization, quantitation and directed therapy using novel target-specific acoustic liposomes.
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