Miniaturized optically generated Bessel beam ultrasound for volumetric transcranial brain stimulation
Yueming Li, Guo Chen, Tiago R. Oliveira, Nick Todd, Yong-Zhi Zhang, Carolyn Marar, Nan Zheng, Lu Lan, Nathan McDannold, Ji-Xin Cheng, Chen Yang
Science Advances 2026, 12 · 10.1126/sciadv.adz7708
Abstract
Noninvasive stimulation of small, variably shaped brain subregions is crucial for advancing our understanding of brain functions. Current ultrasound neuromodulation faces two major trade-offs when targeting brain subregions: miniaturization versus volumetric control and spatial resolution versus transcranial capability. Here, we present an optically generated Bessel beam ultrasound (OBUS) device designed to overcome these limitations. This miniaturized device, measuring 2.33 millimeters in diameter, delivers a column-shaped field achieving a lateral resolution of 152 micrometers and an axial resolution of 1.93 millimeters, enabling targeting of brain subregions with an elongated volume of tissue activation. Immunofluorescence imaging of mouse brain slices confirms its ability to stimulate cells at depths up to 2.1 millimeters. In addition, OBUS outperforms conventional Gaussian ultrasound in transcranial transmission efficiency and beam shape preservation. Electrophysiological recordings and functional MRI captured rodent brain responses evoked by OBUS, demonstrating OBUS's ability to noninvasively activate neural circuits in intact brains. This technology offers expanded possibilities for studying brain functions with precision and volumetric control.
Abstract via europepmc.
Exposures
Exposure 1: OBUS c-Fos activation of motor cortex (mouse)
Target: motor cortex — “motor cortex”
Device: custom-built · OBUS (optically generated Bessel beam ultrasound device)
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 10,600 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.25 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 25 | ✓✓✓ |
| Sonication duration (s) | 3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 4,600 | ✓✓✓⚑ |
OBUS operated with a laser fluence of 68 μJ/mm2 (peak-to-peak pressure 4.6 MPa at focus, 1 kHz laser/acoustic pulse repetition rate), delivered as 3000-pulse trains every 12 s (3 s on, 9 s off; 25% duty cycle) for a total of 30 min, targeted at the motor cortex through the intact (fur-removed) skull with a 0.5 mm gel gap.
Exposure 2: OBUS stimulation of somatosensory cortex (S1): mouse LFP recordings and rat fMRI
Target: primary somatosensory cortex — “somatosensory cortex (S1)”
Device: custom-built · OBUS (optically generated Bessel beam ultrasound device)
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 10,600 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.33 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 33 | ✓✓✓ |
| Sonication duration (s) | 10, 15swept | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 2,800, 3,700, 4,100, 4,900swept | ✓✓✓⚑ |
Mouse LFP: craniotomy, OBUS at 1 kHz PRF, peak-to-peak pressures 2.8/3.7/4.1 MPa, each stimulation a 10 s pulse train followed by 20 s rest within a 1-min cycle (33% duty cycle, the highest of the three paradigms used in the study); 3-min recordings (1 min baseline, 1 min during, 1 min after). Rat fMRI: cranial-window exposed somatosensory cortex, OBUS at 4.9 MPa peak-to-peak, 1 kHz PRF, 15 s on / 45 s off blocks over seven modulation blocks. Control experiments (laser at 0 mW; OBUS repositioned to contralateral S1; light leakage without the OBUS device) confirmed responses were not due to electrical/optical artifact or cochlear activation.
Flags from extraction
n_subjects— Three separate sub-experiments with different animals/species: c-Fos (N=3 mice), LFP electrophysiology (N=4 mice), fMRI (N=2 rats); given as a list rather than summed, and species differ between exposures.exposures[1].unspecified_domain.pressure_kpa— 4.9 MPa (rat fMRI condition) is stated in a separate sentence from the 2.8/3.7/4.1 MPa mouse LFP values and is not included in the list because it is not covered by the same source quote; described in protocol_description instead.exposures[0].unspecified_domain.pressure_kpa— Pressure is stated as a device operating parameter (peak-to-peak, at the focus) without specifying whether it reflects free-field/water calibration or an in-situ/through-skull value; placed in unspecified_domain.exposures[0].timing.pulse_duration_ms— The device's laser pulse width (2.2 ns) is a source characterization parameter, not a stated stimulation 'pulse duration'; left not_reported.auditory_control— The contralateral-placement control is aimed at ruling out cochlear/auditory-mediated activation but is a spatial control rather than a masking or deafening procedure; coded as other.