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An Optimized Miniaturized Ultrasound Transducer for Transcranial Neuromodulation

Chenxue Hou, Yan Wu, Chunlong Fei, Zhihai Qiu, Zhaoxi Li, Xinhao Sun, Chenxi Zheng, Yintang Yang

Frontiers in Neuroscience 2022 · 10.3389/fnins.2022.893108

rodenthealthyemg mep

Abstract

Transcranial ultrasound stimulation (TUS) is a young neuromodulation technology, which uses ultrasound to achieve non-invasive stimulation or inhibition of deep intracranial brain regions, with the advantages of non-invasive, deep penetration, and high resolution. It is widely considered to be one of the most promising techniques for probing brain function and treating brain diseases. In preclinical studies, developing miniaturized transducers to facilitate neuromodulation in freely moving small animals is critical for understanding the mechanism and exploring potential applications. In this article, a miniaturized transducer with a half-concave structure is proposed. Based on the finite element simulation models established by PZFlex software, several ultrasound transducers with different concave curvatures were designed and analyzed. Based on the simulation results, half-concave focused ultrasonic transducers with curvature radii of 5 mm and 7.5 mm were fabricated. Additionally, the emission acoustic fields of the ultrasonic transducers with different structures were characterized at their thickness resonance frequencies of 1 MHz using a multifunctional ultrasonic test platform built in the laboratory. To verify the practical ability for neuromodulation, different ultrasound transducers were used to induce muscle activity in mice. As a result, the stimulation success rates were (32 ± 10)%, (65 ± 8)%, and (84 ± 7)%, respectively, by using flat, #7, and #5 transducers, which shows the simulation and experimental results have a good agreement and that the miniaturized half-concave transducer could effectively converge the acoustic energy and achieve precise and effective ultrasonic neuromodulation.

Abstract via europepmc.

Speciesmouse
Subjects6 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsemg mep — EMG response success rate and latency in triceps
Direction of effectexcitatorySonication of the motor cortex evoked forelimb EMG responses; success rates were (32 ± 10)%, (65 ± 8)% and (84 ± 7)% for flat, #7 and #5 transducers.
Adverse eventsnot reported

Exposures

Exposure 1: Half-concave miniature transducers (#5, #7.5) and flat control, mouse motor cortex

Target: primary motor cortex — “primary motor cortex”
Device: custom-built · half-concave dimpled pic255 single-element transducer, 5 mm diameter ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)400✓✓✓⚑
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.4 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)40✓✓✓
Sonication duration (s)0.2✓✓✓⚑
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 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)1,600✓✓✓⚑
Protocol, in the paper’s words

Sonication parameters were PRF 1 kHz, 40% duty cycle, 200 ms per trial; 20 trials per animal. Pulse duration not stated; whether the 200 ms is the whole train is not spelled out.

Flags from extraction

  • exposures[0].fundamental_frequency_khz — Abstract says transducers were characterised at their thickness resonance of 1 MHz, but the methods and acoustic measurements state 400 kHz; the stimulation frequency in the mouse experiment is not stated separately.
  • exposures[0].unspecified_domain.pressure_kpa — 1.6 MPa appears only in a figure legend with no domain stated; same value reported for all transducers.
  • exposures[0].timing.sonication_duration_s — 200 ms is listed unlabelled alongside PRF and duty cycle; read as train duration (latency window is also 200 ms).
  • sham_type — Figure 9 legend shows a sham condition; its mechanism is not described.
  • exposures[0].device.family — Transducers fabricated in-house from pic255 ceramic; no maker of the finished transducer named.