High-fidelity transcranial ultrasound multi-focal stimulation via physics-aware hologram technique.

Area of Science:

• Neuroscience
• Biomedical Engineering
• Acoustics

Background:

• Transcranial ultrasound stimulation (TUS) offers deep brain access but faces limitations in generating complex acoustic fields for multi-target stimulation.
• Challenges include focal distortion, off-target exposure, and reduced neuromodulation reliability due to skull-induced acoustic field distortions.

Purpose of the Study:

• To introduce a physics-aware hologram technique for precise, multi-target transcranial ultrasound neuromodulation.
• To overcome limitations of conventional methods by ensuring consistency between numerical field synthesis and physical acoustic realization.

Main Methods:

• Developed a physics-aware hologram technique for generating fabrication-ready holographic implementations.
• Enabled accurate formation of single-, dual-, and tri-focal stimulation patterns under transcranial conditions.
• Validated the technique through in silico simulations, ex vivo skull acoustic measurements, and in vivo experiments.

Main Results:

• Achieved improved focal reconstruction, enhanced energy confinement, and reduced off-target acoustic leakage compared to state-of-the-art methods.
• Demonstrated in vivo efficacy in a neuropathic pain mouse model with simultaneous bilateral thalamic stimulation.
• Observed reduced c-Fos expression and preliminary improvements in pain-related behaviors, indicating functional relevance.

Conclusions:

• The proposed technique provides a practical strategy for high-precision, multi-target transcranial neuromodulation.
• This approach enhances spatial localization and reproducibility of in vivo neuromodulation.
• Supports further investigation of this technique for neuroscience research and therapeutic applications.