| In the past two decades, perfluorocarbon (PFC) droplets have been investigated for biomedical applications in several imaging modalities. More recently, interest has increased in 'phase-change' PFC droplets (or 'phase-change' contrast agents (PCCAs)), which can convert from liquid to gas with an external energy input. In the field of ultrasound, phase-change droplets present an attractive alternative to traditional microbubble agents for many diagnostic and therapeutic applications.;In this thesis, new techniques are presented to enhance the performance of PCCAs and ultimately drive the platform closer to clinical use. It is demonstrated that the efficiency of activation can be improved by incorporating highly volatile compounds, and new particle generation methods are developed to produce PCCAs from these compounds. Next it is shown that these methods can be adapted to highly tune the performance of the droplets with regard to both sensitivity to ultrasound and thermal stability - allowing one to 'tune' the droplets for an intended application. Next, an alternative method of determining appropriate ultrasound activation parameters for nanoscale emulsions is demonstrated based on changes in the bubble population produced. Through high-speed video microscopy,the physics of particle expansion after droplet activation are studied to show that droplets produce unique, size-dependent acoustic 'signatures' during vaporization that can be detected at diagnostic ultrasound frequencies and used to isolate droplet vaporization events from tissue and standard microbubble contrast agents. Finally, the benefits of these techniques both in vitro and in vivo are demonstrated in applications such as ultrasound diagnostic and molecular imaging, ultrasound-mediated tissue ablation, and drug delivery across the blood-brain barrier.;The results shown here demonstrate that PCCAs can be highly tuned to perform ideally across a wide range of ultrasound-related applications, which bolsters the argument for their use as diagnostic and therapeutic clinical ultrasound agents. Future refinement of the techniques in this thesis will help drive PCCAs toward eventual use in improving human health. |
