Addressing complex human brain diseases, such as Parkinson’s disease, requires technology that can precisely and flexibly target multiple affected regions simultaneously. Traditional approaches often fall short due to their invasive nature and limited precision.
Researchers at Washington University in St. Louis have made significant strides in this field by developing a groundbreaking noninvasive technology. This innovation, which combines a holographic acoustic device with genetic engineering, allows for the precise targeting of neurons in the brain, opening new avenues for treating neurological disorders.
Development of AhSonogenetics
The new technique, known as AhSonogenetics (Airy-beam holographic sonogenetics), was pioneered by Hong Chen, an associate professor of biomedical engineering and neurosurgery, along with her team. This approach utilizes a noninvasive wearable ultrasound device to modify genetically selected neurons in mice brains. The proof-of-concept study demonstrating this technology was published in the *Proceedings of the National Academy of Sciences* on June 17.
AhSonogenetics integrates several of Chen’s previous advancements into a single, cohesive technology. In 2021, Chen’s team introduced Sonogenetics, a method employing focused ultrasound to deliver viral constructs containing ultrasound-sensitive ion channels to genetically selected neurons. By applying low-intensity focused ultrasound, they could activate these neurons through a small burst of warmth that opened the ion channels. This was the first instance where sonogenetics was shown to modulate the behavior of freely moving mice.
In 2022, the team designed and 3D-printed a flexible tool called an Airy beam-enabled binary acoustic metasurface. This tool allowed for the precise manipulation of ultrasound beams, adding a new layer of control. The ongoing development of Sonogenetics 2.0 aims to combine ultrasound and genetic engineering for noninvasive and precise neuromodulation in both humans and animals. AhSonogenetics synthesizes these advancements to create a potential intervention method for neurodegenerative diseases.
Technological Advantages and Capabilities
“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,” said Chen.
Sonogenetics offers precise control over brain activity, while the airy-beam technology allows researchers to bend or steer sound waves, generating intricate beam patterns within the brain at high spatial resolution. According to Yaoheng (Mack) Yang, a postdoctoral research associate and one of the technology’s developers, AhSonogenetics offers three distinct advantages:
1. Precision: The ability to target smaller brain regions more accurately than conventional methods.
2. Flexibility: The capability to steer sound waves to specific brain regions.
3. Multitargeting: The ability to simultaneously target multiple brain regions.
Chen’s team, including first authors Zhongtao Hu and Yang, meticulously designed each Airy-beam metasurface to serve as the foundation for the wearable ultrasound devices, tailoring them for various applications and precise brain locations.
Testing and Applications
The researchers tested AhSonogenetics on a mouse model of Parkinson’s disease. They successfully stimulated two brain regions simultaneously within a single mouse, thus avoiding the need for multiple implants or interventions. This dual stimulation alleviated Parkinson’s-related motor deficits, such as slow movements, difficulty walking, and freezing behaviors.
One significant advancement of the Airy-beam device is its ability to overcome some limitations of traditional sonogenetics. This includes customizing the device’s design to target specific brain locations and incorporating the flexibility to adjust target locations within a single brain. The device, costing approximately $50 to produce, can be resized to fit various brain sizes, thereby expanding its potential applications.
“This technology can be used as a research platform to accelerate neuroscience research due to its capability to flexibly target different brain regions,” said Hu. “The affordability and ease of fabrication lower the barriers to the widespread adoption of our proposed devices by the research community for neuromodulation applications.”
The development of AhSonogenetics represents a significant leap forward in the precise and flexible modulation of brain activity, offering new hope for the treatment and understanding of complex neurological disorders.
