Nanobubble Activation for Precise Brain Neuromodulation

Published:

Key Points

  • A preclinical study combined nanobubble delivery with low-frequency focused ultrasound to precisely localize the effects of brain neuromodulation.
  • This technique could eliminate the need for genetic modification when performing highly localized brain neuromodulation.
Ultrasound contrast-mode images of PGVs-injected mice brains at several injected days. PGVs collapsed with destructive insonation.
Source: Hou, X., Jing, J., Jiang, Y. et al. Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice. Nat Commun 15, 2253 (2024). https://doi.org/10.1038/s41467-024-46461-y

Nanobubble-Actuated Ultrasound Neuromodulation for Selectively Shaping Behavior in Mice 

The biomedical engineering team at Hong Kong Polytechnic University that is led by Lei Sun, PhD, conducted a preclinical study combining region-specific nanobubble delivery with low-frequency focused ultrasound for brain neuromodulation. The technique elicited responses in both the motor cortex and in deep brain structures. Motor cortex modulation resulted in electromyography (EMG) signaling and limb movement, whereas the distinct behaviors of freezing and rotation were observed when modulating deep brain structures. 

If translatable to humans, this technique could eliminate the need for genetic modification when performing highly localized brain neuromodulation because specific, submillimeter delivery of the nanobubbles would cause the desired effects. 

The nanobubbles used in the study were fabricated by the research team; they created PEGylated gas vesicles (“PGVs”) with optimized surface properties. The research-specific focused ultrasound system included components from Olympus, Tektronix, and E&I, Ltd. 

“When we varied the site of the nanobubble delivery, we were able to activate specific motor control (limb movements) or freezing or rotation from manipulation of deep brain structures,” said Dr. Sun. 

The publication also provides evidence for the mechanism of how the PGVs created the reversible neuromodulation effects: the neurons contain mechanosensitive ion channels that respond to calcium ion signaling. 

The neuromodulation treatment appeared to be safe, producing no cellular damage, inflammation, or significant effects on normal brain function. 

See Nature Communications (Open Access) 

Related Stories 

The Piezo1 Gene’s Role in Focused Ultrasound Brain Neuromodulation June 2023 

Investigator Profile: Lei Sun, PhD September 2022 

A New Method for Using Ultrasound Neuromodulation in Deep Regions of the Brain October 2021 

A Cell-Specific Focused Ultrasound Neuromodulation Technique September 2020