Precision ultrasound could treat deep parts of brain without surgery

A non-invasive ultrasound device can stimulate deep parts of the brain with far greater precision than previously achieved, which could help to treat depression, long-term pain and post-traumatic stress disorder.

A low-power ultrasound system can alter activity deep within the brain with far greater precision than previously possible, allowing the organ to be studied in new ways. It will also help brain surgeons plan operations and could be used to treat some conditions directly.

The ultrasound system is used with an MRI scanner
Eleanor Martin et al.

“I think it does open a new avenue for neuroscience,” says Charlotte Stagg at the University of Oxford, whose team created the system. “We can, for the first time, transiently, safely, non-invasively modulate activity in various bits of the deep brain and see what happens in healthy adults.”

Existing non-invasive ways of altering brain activity all have major limitations. For instance, transcranial magnetic stimulation (TMS) uses magnets to induce electrical currents in the brain. TMS is approved in the US for treating conditions such as depression, but it can only penetrate a few centimetres inside the skull and can’t be focused on a small part of the brain.

Another approach, called transcranial electric stimulation, relies on electrodes placed directly on the head. Like TMS, it only affects the outer part of the brain and can’t be precisely targeted.

Ultrasound, by contrast, can penetrate more deeply into the brain and can be focused. High-intensity ultrasound has been used since the 1950s to kill parts of the brain by heating them, for treating tumours, for instance. However, the systems for focusing it are attached directly to the skull with screws, so this technique still involves some surgery.

In 2008, a team discovered that low-intensity ultrasound can stimulate or inhibit neural activity without causing any heating or damage. The mechanism still isn’t fully understood, but it is thought to be a result of ultrasound affecting the ion channels in the membranes of neurons that help conduct nerve signals.

There is now a lot of interest in using low-intensity transcranial ultrasound for treating conditions such as depression, long-term pain and post-traumatic stress disorder, with several trials under way. Although low-intensity ultrasound can be focused, most systems aren’t very precise because the field is still new.

Before now, the state of the art was a system developed by Tom Riis at the University of Utah and his colleagues. It consists of 252 ultrasound sources arranged in two arrays placed on either side of the head and it can focus on a volume of roughly 90 cubic millimetres.

The system developed by Stagg’s team can focus on just 3 cubic millimetres. That’s 30 times more precise than Riis’s team’s system and thousands of times more precise than most other systems, says team member Bradley Treeby at University College London.

This matters because some structures in the brain are millimetres in size. “They’re very closely packed, and they do different things, and they often do opposing things,” says Stagg. “You need to be able to stimulate each individually and this is the first kit we can do that with.”

To achieve this focus, the team arranged 256 ultrasound sources in a helmet that is sealed around the head and filled with water. Before the system is used, each individual’s head has to be scanned.

These scans are used to tailor a plastic face mask that is attached to the helmet to help immobilise the head in a precise position. The scans are also fed into a computer model that takes account of the shape of each individual’s skull to work out how to focus the sound waves. “We put a lot of effort into designing tools so that we can position our focal spot at exactly the location that we want,” says Treeby.

The system is also designed to be used inside an MRI scanner. In experiments on seven volunteers, the team used the scanner to confirm that the system could precisely target parts of a brain region called the lateral geniculate nucleus, involved in vision.

“The spatial resolution and the prolonged modulatory effects are remarkable,” says Jean-François Aubry at Physics for Medicine Paris in France. “I think transcranial ultrasound stimulation is a very promising technology.”

“It is the sharpest focusing I have seen,” says Riis, who says the system will be transformative for research.

However, it is sometimes necessary to target a larger volume for treatments, say Riis, whose team is carrying out several trials. “In many applications, you would not want a focus this small.”

A big disadvantage of the new system is that it requires the head to be shaved. This is because hair traps air bubbles that deflect ultrasound. Stagg says the team is trying to find a way of eliminating the bubbles, such as via a special shampoo. “It’s probably solvable.”


bioRxiv DOI: 10.1101/2024.06.08.597305

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