Brain tumours, brain haemorrhages and neurological and psychological conditions are often hard to treat with medication. And even when effective drugs are available, these tend to have severe side effects because they circulate throughout the brain and not just the area they are meant to treat. In light of this situation, researchers have high hopes of one day being able to provide a more targeted approach that would deliver medications to very specifically defined locations. To this end, they are in the process of developing mini-transporters that can be guided through the dense maze of blood vessels.
Researchers at ETH Zurich, the University of Zurich and the University Hospital Zurich have now managed for the first time to guide microvehicles through the blood vessels in the brain of an animal using ultrasound.
Ultrasound instead of magnetism
Compared to alternative navigation technologies such as those based on magnetic fields, ultrasound offers certain benefits. Daniel Ahmed, Professor of Acoustic Robotics at ETH Zurich and supervisor of the study, explains: “In addition to being widely used in the medical field, ultrasound is safe and penetrates deep into the body.”
For their microvehicle, Ahmed and his colleagues used gas-filled microbubbles coated in lipids – the same substances that biological cell membranes are made of. The bubbles have a diameter of 1.5 micrometres and are currently used as contrast material in ultrasound imaging.
As the researchers have now shown, these microbubbles can be guided through blood vessels. “Since these bubbles, or vesicles, are already approved for use in humans, it’s likely that our technology will be approved and used in treatments for humans more quickly than other types of microvehicles currently in development,” Ahmed says. He was awarded a Starting Grant by the European Research Council ERC in 2019 for his project to research and develop this technology.
Another benefit of the ultrasound-guided microbubbles is that they dissolve in the body once they’ve done their job. When using another approach, magnetic fields, the microvehicles have to be magnetic, and it’s not easy to develop biodegradable microvehicles. Moreover, the microbubbles developed by the ETH Zurich researchers are small and smooth. “This makes it easy for us to guide them along narrow capillaries,” says Alexia Del Campo Fonseca, a doctoral student in Ahmed’s group and lead author of the study.
Going against the flow
Over the past few years, Ahmed and his group have been working in the lab to develop their method for guiding microbubbles through narrow vessels. Now, in collaboration with researchers from the University of Zurich and University Hospital Zurich, they have tested this method on blood vessels in the brains of mice. The researchers injected the bubbles into the rodents’ circulatory system, where they are swept along in the bloodstream without any outside help. However, the researchers managed to use ultrasound to hold the vesicles in place and guide them through the brain vessels against the direction of blood flow. The researchers were even able to guide the bubbles through convoluted blood vessels or get them to change direction multiple times in order to steer them into the narrowest branches of the bloodstream.