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A New Multi-Mode, High Pressure Portable Transcranial Ultrasound Stimulation System

Zhiwei Li, Zhengxuan Zhou, Xiaoyu Zhang, Yulin Wang, Hanwen Wang, Yingwei Li, Xiaoli Li

IEEE Transactions on Biomedical Engineering 2025 · 10.1109/tbme.2024.3486748

ex vivo tissuehealthyinvasive electrophysiology

Abstract

Objective Transcranial ultrasound stimulation (TUS) is a promising non-invasive neuromodulation method for brain disorders. Commonly-used TUS systems in research include custom-built and commercial devices. Custom-built devices typically consist of traditional function generator, power amplifier, and ultrasound transducer. Due to cumbersome wiring and absence of dedicated control software, the operation of these devices is inconvenient. Commercial devices often have limited waveform modes and cannot perform ultrasound modulation with complex waveforms. These limitations limit the application of TUS technology by ordinary users. Therefore, we propose a portable TUS system with multiple modes and high acoustic pressure. Methods The proposed portable TUS system utilizes a high-power multi-mode stimulator, and an ultrasound transducer with impedance matching module to achieve multiple modes and high acoustic pressure ultrasound neuromodulation. Results The stimulator can output four types of waveforms: continuous pulse continuous stimulus (CPCS), intermittent pulse continuous stimulus (IPCS), continuous pulse intermittent stimulus (CPIS), and intermittent pulse intermittent stimulus (IPIS). When using a same transducer, it generates a peak negative pressure that is nearly identical to one produced by a commercial device. And compared to commercial transducer, the peak negative pressure of our transducer is significantly higher, reaching a maximum of 0.95 MPa. Conclusion In-vitro experiments were conducted using rat hippocampal brain slices. The experimental results demonstrated the effectiveness of the TUS system for neural stimulation. Significance It offers a design method of a portable multi-mode, high pressure TUS system, which is used for complex neural modulation research.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects8 animals
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsinvasive electrophysiology — evoked EPSP slope in CA1 (field recording)
Direction of effectinhibitoryEPSP amplitude and slope decreased during ultrasound stimulation; EPSP slope at the end of the first stimulation block was significantly lower than baseline and the inter-stimulus interval.
Adverse eventsnot applicable

Exposures

Exposure 1: IPIS-mode TUS over hippocampal slice

Target: dentate gyrus, brain slice — “DG area of the hippocampus”
Device: custom-built · custom multi-mode stimulator with concave self-focusing PZT-4 transducer and impedance matching module

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)100✓✓✓⚑
Pulse repetition frequency (Hz)5✓✓✓⚑
Duty cycle (%)not reportedpulse duration × PRF gives 50%⚑
Sonication duration (s)not reported⚑
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Pressure, domain unspecified (kPa)450✓✓✓⚑
Protocol, in the paper’s words

IPIS mode: FF = 500 kHz, FV = 70 V, 50 000 fundamental waves per pulse, PRT = 200 ms, 300 pulses per stimulus group, SRT = 20 min, 2 stimulus groups.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa — Peak negative pressure of 0.45 MPa is given for the transducer with collimator used in the slice experiment; medium of the measurement not stated, so placed in unspecified_domain (paper measures acoustic fields in a water tank elsewhere). Peak negative pressure, not peak pressure.
  • exposures[0].timing.pulse_repetition_frequency_hz — PRF derived from the stated pulse repetition time PRT = 200 ms (unit conversion, 5 Hz).
  • exposures[0].timing.pulse_duration_ms — Pulse is 50 000 fundamental cycles at 500 kHz; pulse duration in ms is not stated, so left not_reported.
  • exposures[0].timing.sonication_duration_s — Protocol: 300 pulses per stimulus group, SRT = 20 min, 2 stimulus groups; duration of one train not stated.
  • exposures[0].target.terms — Transducer fixed over DG; EPSP recorded in CA1 (Fig. 8 legend says CA3 region); mapped to dentate_gyrus.
  • exposures[0].timing.duty_cycle_pct — Duty cycle not stated.