Sound waves make their way to the brain

In the brain, sound waves are riding

Researchers at ETH Zurich have demonstrated, for the first time, that microvehicles can be navigated via mouse brain blood arteries using ultrasound technology. They anticipate that this will ultimately result in therapies that can precisely distribute medications.

The brain's blood supply is intricate, and navigating microvehicles through the bloodstream is a challenging task. (Illustration by Francis Leroy/Science Photo Libraray)

To sum it up

Researchers have now demonstrated that a technology developed at ETH Zurich in recent years for utilizing ultrasound to control microvehicles also functions in the brain.

These microvehicles are harmless gas bubbles that disappear after their purpose is fulfilled.

These microvehicles may carry drugs in the future and be able to transport them to particular locations within the brain. This could lessen the adverse effects of the medications and boost their effectiveness.

It can be challenging to treat neurological and psychological disorders, brain tumors, and brain hemorrhages with medicine. Furthermore, even when effective medications are available, they frequently have serious adverse effects since they affect the entire brain rather than just the targeted area. Given this circumstance, scientists are optimistic that they may eventually be able to offer a more focused method that would administer drugs to precisely designated areas. They are currently working on creating mini-transporters that can be steered through the intricate network of blood vessels in order to achieve this goal.

For the first time, using ultrasound, researchers from ETH Zurich, the University of Zurich, and the University Hospital Zurich have successfully guided microvehicles through an animal's cerebral blood arteries.

Using ultrasound rather than magnetism

Ultrasound has some advantages over other navigational methods, like those that rely on magnetic fields. The study's supervisor, Daniel Ahmed, an ETH Zurich professor of acoustic robotics, says, "Ultrasound is safe and penetrates deep into the body in addition to being widely used in the medical field."

Ahmed and his associates utilized gas-filled microbubbles covered in lipids—the same materials found in biological cell membranes—for their microvehicle. Currently, the 1.5 micrometer-diameter bubbles are utilized as contrast material in ultrasonic imaging

It has now been demonstrated by the researchers that these microbubbles may be directed into blood arteries. "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 continues. The European Research Council (ERC) gave him a Starting Grant in 2019 for his initiative to investigate and advance this technology.

The fact that the ultrasound-guided microbubbles dissipate in the body after serving their purpose is another advantage. It is difficult to create biodegradable microvehicles when employing a different method that uses magnetic fields since the microvehicles must be magnetic. Furthermore, the researchers at ETH Zurich created smooth, tiny microbubbles. Lead study author and PhD student in Ahmed's lab Alexia Del Campo Fonseca explains, "This makes it easy for us to guide them along narrow capillaries."

Defying the norm

Ahmed and his team have been refining their technique for guiding microbubbles through tiny channels in the lab over the last few years. Together with scientists from University Hospital Zurich and the University of Zurich, they have now tested this technique on mouse brain blood arteries. The bubbles were injected by the researchers into the mice' circulatory systems, where the bloodstream carries them naturally. Nevertheless, the vesicles were able to be guided through the brain veins against the direction of blood flow by the researchers using ultrasound to hold them in place. Even more impressively, the researchers managed to drive the bubbles through coiled blood channels or have them shift course several times.

Brain microscopy image showing orange clusters of microvehicles within blood arteries. (Photo: modified by Del Campo Fonseca et al. in Nature Communications 2023)

The researchers additionally affixed four tiny transducers to the exterior of each mouse's skull in order to regulate the motion of the microvehicles. These gadgets produce ultrasonic vibrations that travel in waves throughout the brain. Waves from two or more transducers can either cancel each other out or magnify each other at certain locations in the brain. The researchers use a complex technique to modify the output of each individual transducer in order to direct the bubbles. They can see the direction in which the bubbles are going thanks to real-time imagery.

Two-photon microscopy was employed by the researchers to generate the imagery for this investigation. They intend to improve ultrasound technology for this use as well as the use of ultrasonography itself for imaging in the future.

The microbubbles in this investigation lacked medicine. Initially, the goal was to demonstrate that the microvehicles could be maneuvered via blood veins and that the technique could be applied to the brain. There are encouraging medicinal uses for it there, including as the treatment of cancer, stroke, and mental health issues. The next task for the researchers is to bind medicine molecules to the bubble casing's outside for transportation. In the hopes that it will eventually serve as the foundation for the creation of novel treatments, they aim to improve the entire process to the point where it can be applied to people.