Phase-change contrast agents for medical ultrasound are an alternative to currently approved (FDA) microbubbles. While gaseous microbubbles are restricted to intravascular applications due to their large size, phase-change contrast agents are delivered as liquid nanodroplets (&lt;200 nm in diameter), small enough to freely diffuse past the vessel wall or into diseased tissues. To produce ultrasound contrast, the agents are locally activated using either an acoustic or laser pulse to form transient microbubbles. As a result of their small size, interfacial forces may play a significant role in stabilizing droplets, suppressing spontaneous vaporization. Consequently, methods for producing monodisperse liquid nanodroplets from volatile perfluorocarbons (PFCs) are needed to enable new medical imaging and therapeutic technologies.<br/>Spontaneous emulsification or the ‘ouzo effect’ is a new and efficient method of generating droplet contrast agents. The process begins with dissolving a perfluorocarbon liquid or gas in a good solvent such as ethanol. Once a poor solvent, such as water, is added to the saturated alcohol the solvent quality reduces and leads to the formation of monodisperse nanodroplets. The size of the nanodroplets a can range from approximately 100 nm up to several &gt;2 mm in diameter. Furthermore, activation thresholds can be modulated by varying the PFC volatility. Moreover, photoacoustic agents can also be designed by coating the interface with a near-infrared light absorbing material. By combining the effects of photothermal heating with the tensile load from the acoustic wave, the activation threshold of agents can be reduced by as much as two orders of magnitude. We demonstrate that a clinical ultrasound imaging array fitted with an optical fiber bundle can be used to electronically steer and selectively activate the agents within phantom materials. These features can be beneficial in precision droplet cavitation for therapeutic applications, such as the mechanical breakdown of blood clots and tumors.

Design and synthesis of phase-change contrast agents for ultrasound-based imaging

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.