A team of biomedical engineers at the Washington University in St. Louis have developed a noninvasive technology that combines a holographic acoustic device with genetic engineering to precisely modulate selected neurons in the multiple diseased regions of the brain. The technology has significant potential to treat human brain diseases, such as Parkinson’s disease that involve damage in more than one brain region.
The technology, called AhSonogenetics (Airy-beam holographic sonogenetics) uses a noninvasive, wearable ultrasound device and showed in mouse studies that it is capable of altering genetically selected neurons in the brain. The technology, detailed in a paper published this week in Proceedings of the National Academy of Sciences, builds on several advances from the lab of Hong Chen, an associate professor of biomedical engineering and neurosurgery at Washington University in St. Louis who is the senior author of the study.
In 2021, the Chen lab launched Sonogenetics, a focused ultrasound device that delivers a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain. The ultrasound delivers a small burst of warmth which opens the ion channels and activates the neurons and the Washington University team was the first show this method could alter the behavior of freely moving mice.
A year later, Chen and her team designed and 3D-printed a more versatile tool that allowed them to manipulate ultrasound beams. The lab is also developing Sonogenetics 2.0 which allows for the noninvasive and precise modulation of defined neurons in the brains of humans and animals. AhSonogenetics is a combination of the two technologies.
“By enabling precise and flexible cell-type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders,” Chen said.
A powerful feature of the new technology is its ability to flexibly stimulate either the left or right striatum in a single mouse, which is achieved by switching the acoustic metasurface in the wearable ultrasound device. In this way, the device eliminates the need for multiple implants or interventions.
“Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson’s disease mice,” the study authors write. “This advancement is significant since many neurological disorders, including Parkinson’s disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type–specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.”
Yaoheng (Mack) Yang, PhD, a postdoctoral research associate who earned a doctorate in biomedical engineering from McKelvey Engineering in 2022, noted that Sonogenetics provides researchers with the ability to precisely control brains. The airy-beam technology allows researchers to bend or steer the sound waves to generate arbitrary beam patterns inside the brain with a high spatial resolution a significant advance compared with current wearable ultrasound devices.
According to Yang, the combined technologies provide three distinct advantages: “Airy beam is the technology that can give us precise targeting of a smaller region than conventional technology, the flexibility to steer to the targeted brain regions, and to target multiple brain regions simultaneously.”
The new technique was tested on mouse models of Parkinson’s disease and the researchers showed they were able to stimulate two distinct brain regions simultaneously. The stimulation improved many of the usual motor symptoms of Parkinson’s disease including slow movements, difficulty walking, and freezing behaviors.
The new device costs only about $50 to make and can be tailored to fit a variety of brain sizes.
“This technology can be used as a research platform to speed neuroscience research because of the capability to flexibly target different brain regions,” said Zhongtao Hu, PhD, a former postdoc in the Chen lab who, along with Yang, designed each Airy-beam metasurface. “The affordability and ease of fabrication lower the barriers to the widespread adoption of our proposed devices by the research community for neuromodulation applications.”
