Researchers use Ultrasound Holograms to Influence Brain Networks

The first picture taken of a person nowadays is usually an ultrasound scan in the womb. But the technology is capable of much more than that. Physiotherapists have long used ultrasound to heat bodily tissues, and oncological surgeons use high-intensity ultrasound - and the heat it generates inside the body - to destroy tumors.

Over the last decade, scientists have also been researching how low-intensity ultrasound can be used to influence neural activity in the brain in a targeted manner. Initial clinical trials are already seeking to verify whether this "neuromodulation" could help to alleviate the symptoms of Alzheimer's or epilepsy, or the shaking of tremor patients.

Now, researchers from ETH Zurich, the University of Zurich and New York University have succeeded in improving the technique of ultrasonic stimulation in the brain. The scientists have developed a device that, for the first time, allows them to stimulate three or up to five precisely defined points in the brain simultaneously, as they demonstrate in their study. Until now, this was only possible to some extent - and with much less precision.

"Given that the brain operates in networks, it's easier to activate or inhibit a brain network if you stimulate it at multiple points simultaneously," explains Daniel Razansky, a professor at ETH Zurich and the University of Zurich. Razansky led the work together with a colleague from New York University.

In this method, neuromodulation is performed through the skull by placing the device on top of the head. This is a non-invasive technique - in other words, there is no need for craniotomy or any other surgical intervention.

The researchers performed neuromodulation on mice in the laboratory. For this, they positioned the mouse head in the center of a hood equipped with several hundred ultrasound transducers developed by the researchers.

With the help of sophisticated stimulation electronics, these transducers generate brief ultrasound pulses in such a way that the ultrasound waves interfere with each other within the brain. The principle is similar to a hologram, an apparently three-dimensional image that is produced by the interaction between light waves. In the new method developed by the researchers from Zurich and New York, individual focal points are produced by overlaying a large number of ultrasound waves.

By modulating brain networks at multiple locations at the same time, the researchers can work with lower ultrasound intensity as compared to single-spot stimulations. "The less intense the ultrasound, the safer this process is for the brain," explains Razansky. Earlier approaches to ultrasonic neuromodulation often suffered from an all-or-nothing effect: if the ultrasound was too weak, it had no effect, whereas an excessively high intensity led to uncontrolled excitation of the entire brain, which carried a risk of brain damage. Moreover, intense ultrasound may cause vascular damages and other unwanted overheating effects in the brain or the skull.

Low-intensity focused ultrasound pulses have short-term effect, including brief temperature rises in the focal area. Moreover, it is thought that they also influence channel proteins that are found on the surface of neurons, and which control the transport of ions into and out of cells. Which mechanisms contribute to the activation and inhibition of neurons - and to what extent - is something that researchers still have to investigate in detail.

The new method can be used not only to activate brain networks but also to simultaneously visualize this activation by means of imaging, so researchers can immediately see which networks have been activated.

The most recent study, which the researchers published in the journal Nature Biomedical Engineering, served to develop the technology and was not aimed at a medical application.

This study and the collaboration with researchers from New York University were principally financed by the United States National Institutes of Health. As this agency is currently under political pressure and is no longer awarding funding to international research partners, it is presently not possible for the researchers to continue their collaboration within the same framework, explains Razansky. However, he would like to continue the work to the best of his ability with other funding sources.

Next, the researchers want to focus on applications and test the technology in various animal models of brain diseases. In addition to Alzheimer's, tremor, and epilepsy, other potential medical applications include depression, Parkinson's, and stroke recovery treatments. "We rely on animals for our research," says Razansky. "It won't be possible to research these developments at such an early stage in humans. We first need to learn how to control the intervention and ensure that it is safe and effective for the treatment of brain diseases."

Razansky's group specializes in the development of ultrasound and optical imaging techniques - specifically, in the system engineering aspects, experimental methods, and data analysis. The colleagues from New York contributed their expertise in the field of neuroscience. The device's development and the experiments took place in Zurich.

Prof. Dr. Daniel Razansky
University of Zurich and ETH Zurich
Institute of Pharmacology und Toxicology (IPT) and
the Neuroscience Center's research group Biomedical Technology and Imaging (IBT)

Multiscale Functional and Molecular Imaging Razansky Lab