The skull is so effective at protecting the brain that it has impeded the progress of neuroscience.
In particular: A nice, thick skull poses challenges for imaging the brain in natural environments or while a person is moving.
Meanwhile, with the recent advent of ultrafast ultrasound, the possibility of studying and monitoring real-time microvascular brain activity poses a novel opportunity for neuroscientists, from better understanding dementia to increased accuracy during neurosurgery to revolutionizing treatment for comatose patients.
Now, a team of Dutch researchers has shown that a mobile ultrafast ultrasound scanner — functional ultrasound imaging (fUSi) — affixed inside a three-dimensional printed helmet can image brain activity in a patient pushing a cart while walking and performing everyday tasks in an everyday environment (it was not wireless — they used a 100-m-long extension cord).
“We’ve basically shown that functional ultrasound imaging is a technique that can be a high-resolution mobile brain scanner for the research side, and if you’re looking from a medical side, I would say that now the brain is not a black box anymore,” said Sadaf Soloukey, MD, PhD, neurosurgical resident at Erasmus MC in Rotterdam, the Netherlands, and lead author of the paper published recently in Science Advances. “We now with ultrasound have the possibility to see directly in real time inside the brain.”
How They Made It Work
The study involved two patients with artificial skull implants and included sensory, motor, and multitasking experiments generating reproducible data over 21 months. One of the patients died partway through the study due to tumor regrowth, despite being tumor progression-free for multiple years. Both patients had PEEK implants; the second patient’s implant was placed following a high-velocity trauma.
The skull implants are key for the acoustic requirements of ultrasound. That’s less limiting than one may think because these are the patients researchers want to study anyway, said Charles Liu, MD, PhD, a professor of neurological surgery and director of the University of Southern California Neurorestoration Center in Los Angeles.
“They’re a natural patient population,” said Liu, who wasn’t involved in the study but published a 2024 paper in Science Translational Medicine that also used fUSi to visualize brain activity during video game and guitar playing by an individual with a skull implant.
Liu recalled that when the researcher Mickael Tanter, PhD, and his team in France first published on the topic of ultrafast ultrasound, people were skeptical.
The potential for fUSi is apparent “when another group publishes something that essentially corroborates what you said in relatively short order in another big journal,” Liu said.
Why Ultrafast Ultrasound Is so Promising
One reason: Ultrafast ultrasound can record 10,000 frames per second.
“That allows you to separate the tiny blood flow in the brain from the motion of the brain,” explained Pieter Kruizinga, PhD, an imaging physicist and co-author of the Science Advances paper. “The tiny blood flow in the small vessels is responsible for neurovascular coupling, so you really need this ultrasound on steroids. It’s the workhorse in our lab to look at brain perfusion, basically. And the frequencies we use, they don’t penetrate through the skull. Why you see a child in a womb so nicely is because you have this water, and then it hits the skull, and you get all these nice signals from it. But to penetrate through the skull is very difficult.”
Liu noted that there is some early research examining ways to overcome the skull challenge, such as some coming out of the French lab led by Tanter using nanobubbles as a contrast agent. New fUSi technology would also be ideal for working with people who have implanted neuromodulation devices such as deep brain stimulators, Liu said. His own upcoming research involves imaging the spinal cord during the filling and emptying of the human bladder.
Brain surgery applications of fUSi are also on the horizon. Presurgical functional MRI (fMRI) is usually used as a map by neurosurgeons heading into surgery, and once underway, they move to relying on cortical stimulation to make decisions.
During surgery, the fMRI map is often “no longer relevant because things shift; the brain can swell out or drop in, and even as your surgery is progressing, things can move. Sometimes when I’m taking out a tumor, different parts might collapse,” said Richard G. Everson, MD, an assistant professor of neurosurgery at UCLA. “Having a portable, repeatable system that we can operate in a handheld manner like an ultrasound would be a really great instrument to have. I think the writing is on the wall that this will and can work, but it’s certainly not at any sort of level of being clinically ready.”
Everson’s team has already been using fUSi outside of the operating room to evaluate patients who have had surgery to remove part of the skull for a variety of reasons.
Also Needed: More Processing Speed
The next key steps for fUSi to come to the operating room are for data processing technology to allow for real-time information and benchmarking, he said, because “if it takes an hour to analyze the data, that’s no good because the surgery’s already over.”
Following brain surgery, there are limited techniques to monitor what’s happening in the brain.
“So we have, unfortunately, a lot of patients in the ICU after trauma that are waiting often to show whether or not they will wake up,” Soloukey said, and many of them have had a hemicraniectomy like the main patient in her team’s study.
In 2020, her team published a paper demonstrating the use of fUSi during awake brain surgery.
Future research could examine “If there are some functional networks that are, let’s say, a good signature of someone waking up with a coma, then it might be easier not only to monitor their progress but to predict how they might wake up,” Soloukey said. “And this is, of course, something that’s very, very difficult. It’s a sensitive topic. I know that the US and Europe also think differently about these subjects. But I think it starts with understanding what happens in a coma and trying to make good tools that can predict a patient’s outcome. Functional ultrasound is a great bedside tool for that in the ICU context — because it could be bedside.”
Astronauts on trips to Mars will need more nutritional and psychologically satisfying food. (Credit : Kavin Gill)
