Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment becomes difficult as bioeffects can occur outside of the target region. Spatial control of gas bubbles can be achieved with acoustic vaporization of perfluorocarbon droplets. This study was undertaken to determine the acoustic parameters for bubble production by droplet vaporization and how it depends on the acoustic conditions and droplet physical parameters. Droplets of varying sizes were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure. Simultaneous measurements of the vaporization and inertial cavitation thresholds were performed. The results show that droplets cannot be vaporized at low frequency without inertial cavitation occurring. However, the vaporization threshold decreased with increasing frequency, exposure and droplet size. In summary, we have demonstrated that droplet vaporization is feasible for clinically-relevant sized droplets and acoustic exposures.

Focused ultrasound therapy can be enhanced with microbubbles by thermal and cavitation effects. However, localization of treatment becomes difficult as bioeffects can occur outside of the target region. Spatial control of gas bubbles can be achieved with acoustic vaporization of perfluorocarbon droplets. This study was undertaken to determine the acoustic parameters for bubble production by droplet vaporization and how it depends on the acoustic conditions and droplet physical parameters. Droplets of varying sizes were sonicated in vitro with a focused ultrasound transducer and varying frequency and exposure. Simultaneous measurements of the vaporization and inertial cavitation thresholds were performed. The results show that droplets cannot be vaporized at low frequency without inertial cavitation occurring. However, the vaporization threshold decreased with increasing frequency, exposure and droplet size. In summary, we have demonstrated that droplet vaporization is feasible for clinically-relevant sized droplets and acoustic exposures.

Microbubble contrast agents for ultrasound are widely used in numerous medical applications, both diagnostic and therapeutic. Due to their size, similar to that of red blood cells, microbubbles are able to traverse the entire vascular bed, enabling their utilization for applications such as tumour diagnosis. Vaporizable submicron droplets of liquid perfluoro- carbon potentially represent a new generation of extravascular contrast agents for ultrasound. Droplets of a few hundred nanometers in diameter have the ability to extravasate selectively in regions of tumour growth while staying intravascular in healthy tissues. Upon extravasation, these droplets may be vaporized with ultrasound and converted into gas bubbles. In this thesis we argue that vaporized submicron perfluorocarbon droplets possess the necessary stability and acoustic characteristics to be potentially applicable as a new gener- ation of extravascular ultrasound contrast agents. We examine, separately, the ultrasound conditions necessary for vaporization of the droplets into microbubbles, the size and stability of these bubbles following vaporization, on timescales ranging from nanoseconds to minutes, and the bubbles’ acoustic response to incident diagnostic ultrasound. We show that submicron droplets may be vaporized into bubbles of a few microns in diameter using single ultrasound pulse within the diagnostic range. The efficiency of conversion is shown to be on the order of at least 10% of the exposed droplets converting into stable microbubbles. The bubbles are shown to be stabilized by the original coating material encapsulating the droplet precursors, and be stable for at least minutes following vaporization. Finally, vaporized droplets are shown to be echogenic, with acoustic characteristics comparable to these of the commercially available ultrasound contrast agents. The results presented here show that vaporized droplets possess the necessary stability properties and echogenicity required for successful application as contrast agents, suggesting potential for their future translation into clinical practice.

Microbubble contrast agents for ultrasound are widely used in numerous medical applications, both diagnostic and therapeutic. Due to their size, similar to that of red blood cells, microbubbles are able to traverse the entire vascular bed, enabling their utilization for applications such as tumour diagnosis. Vaporizable submicron droplets of liquid perfluoro- carbon potentially represent a new generation of extravascular contrast agents for ultrasound. Droplets of a few hundred nanometers in diameter have the ability to extravasate selectively in regions of tumour growth while staying intravascular in healthy tissues. Upon extravasation, these droplets may be vaporized with ultrasound and converted into gas bubbles. In this thesis we argue that vaporized submicron perfluorocarbon droplets possess the necessary stability and acoustic characteristics to be potentially applicable as a new gener- ation of extravascular ultrasound contrast agents. We examine, separately, the ultrasound conditions necessary for vaporization of the droplets into microbubbles, the size and stability of these bubbles following vaporization, on timescales ranging from nanoseconds to minutes, and the bubbles’ acoustic response to incident diagnostic ultrasound. We show that submicron droplets may be vaporized into bubbles of a few microns in diameter using single ultrasound pulse within the diagnostic range. The efficiency of conversion is shown to be on the order of at least 10% of the exposed droplets converting into stable microbubbles. The bubbles are shown to be stabilized by the original coating material encapsulating the droplet precursors, and be stable for at least minutes following vaporization. Finally, vaporized droplets are shown to be echogenic, with acoustic characteristics comparable to these of the commercially available ultrasound contrast agents. The results presented here show that vaporized droplets possess the necessary stability properties and echogenicity required for successful application as contrast agents, suggesting potential for their future translation into clinical practice.