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Harnessing the “ouzo effect” for better ultrasound imaging

By Lindsey Doermann
January 3, 2019

ouzo effect in pastis

ChemE postdoctoral researcher David Li and professor Lilo Pozzo have developed a method for synthesizing nanodroplets that could unleash new potential for ultrasound imaging and therapies. They recently published their research in Nano Letters, in collaboration with colleagues in UW’s Department of Bioengineering, Applied Physics Lab, and Department of Neurological Surgery.

More and more, physicians are using intravenously injected microbubbles to improve contrast in ultrasound images. Further, they’re exploring how to apply these microbubbles to drug delivery and new therapies. While these substances work well within blood vessels, they are too large, at >1 μm in diameter, to diffuse through vessel walls and into tissues or tumors. If particles were small enough, they could be used to destroy diseased tissue non-invasively, for example.

To address the issue of size, the team developed an agent that can be injected as a liquid, then vaporized in the body with an acoustic pulse to form bubbles. They made this material by harnessing a phenomenon familiar to bartenders and colloid scientists alike: the “ouzo effect.” When water is added to the Greek spirit ouzo, anise oil droplets form spontaneously, turning the drink cloudy. This kind of nucleation also occurs in pastis, sambuca, and absinthe.

In the case of ultrasound contrast agents, the researchers found that they could dissolve perfluorocarbons (PFCs) in ethanol. When they added a water-based solution, the PFC came out of solution and formed nanodroplets on the order of 100 nm in diameter, which is small enough to diffuse out of blood vessels.

Creating this sort of material is particularly challenging: it must exist in a liquid form in order to be injected and diffuse into tissues. But it must also vaporize with sufficiently low-pressure output from a clinical ultrasound scanner in order to be safe for a patient. That meant the researchers needed to synthesize the nanodroplets without inputting energy, lest the PFC evaporate immediately. “This is a big deal for this application because we want to make a very unstable material,” says Pozzo. Hence, the spontaneous nucleation of the ouzo method. 

The team experimented with several PFC blends to optimize the droplets’ stability and activation threshold. Then they tested ouzo-synthesized perfluorobutane droplets in rats, where they were able to successfully image spinal cord tissue.

“The ouzo method is a fast and easy approach to produce nanodroplets with minimal equipment requirements and low costs,” Li writes. With the new method at his disposal, he is now working on using these agents for identifying and pulverizing blood clots to restore blood flow in occluded vessels. And because agents behave differently depending on ultrasound conditions, he says, the ultimate goal is to develop ultrasound sequences that will allow clinicians to use just one contrast agent both for identifying margins of diseased tissues and for treatment.

Photo: The ouzo effect in pastis, via Flickr