Abstract
The primary goal of this dissertation is to apply ultrasound contrast agents (UCAs) to the integrated applications of medical ultrasound imaging. The main topics can be divided to two certain parts. The first part which mainly described in chapter 2 includes the investigations on the fabrication of UCA and the influence of shell compositions on the physic-chemical properties of these agents. The second part focused on the developments of value-added techniques including ultrasound molecular imaging, drug delivery, and bi-model imaging applications that described in chapter 3 and 4. In chapter 2, we described a size controlling technique that based on regulating the compositions of shell materials for improving the oscillation response of bubbles at specific ultrasound frequency. The systemic results indicate that we could use the regulation technique to control the mean sizes of bubbles from 0.93 to 2.86 μm and even to optimize the imaging stability of fabricated bubbles. In chapter 3, we developed a covalently conjugated bubble system coupling with the new class of targeting ligands, aptamers, for providing a high specific affinity for ultrasound targeting studies. Further technical improvements were also made to reduce the required time and avoid the degradation of bubbles during conjugation process. With the optimized process, the conjugation efficiency of targeted bubbles was up to 1.7-fold higher compared with traditional processes. In chapter 4, we turned to the development of the new generation UCA, acoustic phase-change droplets, in the cause of integrating the diagnosis and therapy in one modality. Several ingredients were associated with the acoustic droplets, such as aptamer molecules, anti-cancer drug (doxorubicin) and superparamagnetic iron oxide nanoparticles. With ultrasound insonation, these droplets underwent an instant phase transition into gas bubbles called acoustic droplet vaporization. This instant vaporization process occurred with inertial cavitation while liberating the encapsulated therapeutic drugs in the same time. By utilizing these properties, we purposed a hybrid tumor treatment strategy that integrated both the instant mechanical and long-term chemical therapeutic effects.