Microbubble contrast agents are used to enhance ultrasound images of the vascular space, as non-contrast ultrasound is only very weakly sensitive to blood flow in small vessels. Currently, microbubbles are approved clinically for left ventricular border enhancement in sub-optimal echocardiography, and are used pre-clinically for perfusion imaging and molecular imaging of diseased tissue. However, due to their size, microbubbles cannot leave the blood vessel space and diffuse into the tissue and therefore cannot be used as extravascular contrast agents.
Recently, we have developed phase-change perfluorocarbon nanodroplet emulsions that are small enough to potentially leave the vascular space at tumor sites while in the liquid state and and can be vaporized into microbubbles with additional ultrasound energy. These studies may lead to new methods of tumor-specific diagnostic imaging, drug/gene delivery, and ultrasound-mediated ablation. We have developed further techniques to 'tune' droplet sensitivity to ultrasound and thermal stability through use of highly volatile perfluorocarbons in order to create custom vaporization thresholds, which may be desirable for different applications.
Schematic of a 'microbubble condensation' method to generate phase-change emulsions: Exposing pre-formed PFC microbubbles to decreased ambient temperature and increased ambient pressure results in a condensing of the gaseous core. The decreased size results in an increased Laplace pressure, which serves to preserve the particle in the liquid state. Once exposed to increased temperature and energy delivered via ultrasound, vaporization of the droplet core results in a larger, highly echogenic gas microbubble.