Linking light and sound creates safer noninvasive brain investigations

Tiny devices, some at the nanoscale, are replacing traditional, bulky electronics in the photonics-based world of Chen Yang, a professor of chemistry at Boston University. Yang works in nongenetic photoacoustic neural stimulation, and also has a faculty post in the BU Department of Electrical and Computer Engineering. Her PhD is from Harvard and her other degrees are from Hong Kong University of Science and Technology and the University of Science and Technology of China.

In her Hot Topics presentation, Yang described how her light-and-sound-based systems work; her Jan 28 BiOS talk at SPIE Photonics West was titled “Nongenetic Photoacoustic Neural Stimulation.”

Using sound for imaging has been around for some time, but Yang said, “Our work is moving in a new direction, using light-triggered ultrasound for modulation of biological activity. We are actually converting light energy to mechanical energy with the same frequency as ultrasound.”

Our work is moving in a new direction, using light-triggered ultrasound for modulation of biological activity. We are actually converting light energy to mechanical energy with the same frequency as ultrasound.

This, Yang said, will utilize the noninvasive benefits of ultrasound — a common imaging method in hospitals, particularly with pregnancy testing.

Most pregnancy imaging in the US uses ultrasound to produce baby pictures taken in a mother’s womb. Instead, said Yang, a simpler photoacoustic device may replace the current ultrasound technology, which is based on “bulky electronic parts.”

In Yang’s lab, with a view of Boston’s Charles River, the team works with neuron cell cultures, mice, nanoparticles, fibers and lasers, creating photoacoustic devices to deliver ultrasound targeting a tiny area precisely. Some devices are thinner than a syringe needle. Some are wearables, rather like a pencil-lead eraser, soft, and twistable, to place on a rat or mouse head.

The research goes beyond just making images, using photonics to alter neural activities.

Boston University’s Professor Chen Yang. Credit: Boston University

“Why is this so exciting for us?” Yang said, “Examining baby development through pictures taken with ultrasound is important. Imagine using this new tool for other disease activities, as treatments. Such modulation of neuron activities is something really new,” Yang said.

In the past, clinical work has used implanted electrodes to alter neuron behavior in the brain. Now, Yang says, photoacoustics will offer “a very powerful technique to modulate neuron activity, in a clinical setting, to achieve deep brain stimulation.”

“We are developing a new way of neuron modulation, using light, to generate ultrasound,” Yang said. “There are intriguing potentials for this technology.”

So why the new interest in photoacoustics to go beyond the electron-based approach? Three reasons, says Yang:

1. Expanded precision in the lab
Because the technology covers a finer area of brain tissue, it can produce higher spatial precision. To understand how the brain functions, Yang said, a tool is needed to examine a precise location in the brain see how it responds to stimulation.

“With photoacoustics, we can look at a very small area or volume of brain tissue. And that can apply to any neuron, like in the spinal cord or nerves.

“And it’s not just about study of the brain. With this technology, we can control the brain as well,” she said. The light used in photoacoustics can be integrated into a compact technology with thousands of elements to function as a modulator to change activity or behavior.

2. Greater range and safety
Because the device is not based on electronic parts based on metal, it is more compatible with functional MRI for a patient with an implant into the brain to treat a neuronal disease, like Parkinson’s. Photoacoustics will provide a number of options to learn how a brain responds to treatment, in primate models for now and ultimately in humans.

“We know the neurons respond to ultrasound,” Yang said. “But exactly through what mechanism they respond, we don’t know.“

“Emerging evidence indicates that on neuron membranes, some proteins are sensitive to mechanical disruption. These channels are responsible in photoacoustic modulation,” Yang said, and as the excited neurons are activated, that will generate action potential. It is this firing, she said, that gives us the signals in the brain that drive thinking and behavior. “

A better understanding of how this works will help us design devices with higher efficiency.”

3. Wearable potential
Photoacoustics can be incorporated into a wearable, flexible device for noninvasive brain stimulation, Yang said. “I don’t have to implant this. We would place it outside the skull, an animal skull for now, and can stimulate the animal brain.”

Clinical applications include a new generation of deep brain stimulation. And, said Yang, “We are very excited about the potential for retinal stimulation, and for new designs for a retinal prosthesis.”

Photoacoustic implants can replace the function of damaged photoreceptors, in patients with age-related macular degeneration, or AMD, which affects some 280 million persons in the US.

Current solutions generally involve electrode or photovoltaic implants. Said Yang, “Light triggered ultrasound can activate a retina and generate a signal to the brain to restore tissues.”

French company Axorus is supporting the Yang lab’s work, and anticipates marketing products to help patients with AMD.

Yang first attended a Photonics West event in San Francisco in 2018. She recalled, “I was extremely grateful as it provided connections to many collaborators we are working with now.”

Ford Burkhart is a science and technology writer based in the US. A version of this article appeared in the 2023 Photonics West Show Daily.