PhD, University of Cincinnati, 2008, Engineering : Biomedical Engineering

Ultrasound contrast agents (UCAs) stabilized against gas diffusion in the bloodstream yet triggered for destruction by specially designed pulses of ultrasound are desirable for clinical applications in vivo. Echogenic liposomes (ELIP) are nano-sized phospholipid vesicles that contain both gas and fluid. With incorporation of a drug, such as recombinant tissue-Plasminogen Activator (rt-PA), these liposomes may be able to deliver a high local concentration of rt-PA by site-specific delivery of the drug directly to thrombi, with a lower systemic dose overall. Therefore, it is necessary to assess ELIP stability and destruction thresholds in vitro before their application in clinical diagnostic imaging and targeted drug delivery. Several researchers have used optical and acoustic techniques to identify three dominant mechanisms of UCA destruction; static diffusion, acoustically driven diffusion, and fragmentation (Chomas et al, 2001a; Bouakaz et al., 2005; Porter et al., 2006). We have developed new acoustic techniques to assess these three destruction thresholds of an FDA-approved UCA, Optison®, and unmodified ELIP utilizing a clinical diagnostic ultrasound scanner (Porter et al., 2006; Smith et al., 2007a). Recently, in vitro studies were performed with an innovative drug-encapsulated contrast agent, rt-PA-loaded ELIP. Their stability during contrast imaging was assessed using low output B-mode pulses and rt-PA was found to remain associated with the lipid bilayer. They were also fragmented using color Doppler pulses for determination of drug delivery by spectrophotometrically measuring the concentration of rt-PA released (Smith et al., 2007b). The primary objective of this dissertation was to characterize a novel echogenic lipid-based drug-encapsulated UCA using a diagnostic ultrasound scanner for its potential use in both image-guided and ultrasound-triggered drug delivery.

Committee: Christy K. Holland PhD (Committee Chair); William S. Ball MD (Committee Member); George J. Shaw MD, PhD (Committee Member); T. Douglas Mast PhD (Committee Member) Subjects: Acoustics; Biomedical Research; Engineering; Health; Pharmaceuticals; Physics; Radiology; Scientific Imaging