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Mechanical and mechanothermal effects of focused ultrasound elicited distinct electromyographic responses in mice

Hongchae Baek, Yaoheng Yang, Christopher Pham Pacia, Lu Xu, Yimei Yue, Michael R Bruchas, Hong Chen

Physics in Medicine & Biology 2021 · 10.1088/1361-6560/ac08b1

rodenthealthyemg mepbehaviourother mrihistology molecular

Abstract

The objective of this study was to compare focused ultrasound (FUS) neuromodulation-induced motor responses under two physical mechanisms: mechanical and mechanothermal effects. Mice were divided into two groups. One group was subjected to short-duration FUS stimulation (0.3 s) that induced mechanical effects (mechanical group). The other group underwent long-duration FUS stimulation (15 s) that produced not only mechanical but also thermal effects (mechanothermal group). FUS was targeted at the deep cerebellar nucleus in the cerebellum to induce motor responses, which were evaluated by recording the evoked electromyographic (EMG) signals and tail movements. Brain tissue temperature rise associated with the FUS stimulation was quantified by noninvasive magnetic resonance thermometry in vivo . Temperature rise was negligible for the mechanical group (0.2 °C ± 0.1 °C) but did rise within the range of 0.6 °C ± 0.2 °C-3.3 °C ± 0.9 °C for the mechanothermal group. The elongated FUS beam also induced heating in the dorsal brain (below the top skull) and ventral brain (above the bottom skull) along the beam path for the mechanothermal group. Both mechanical and mechanothermal groups achieved successful FUS neuromodulation. EMG response latencies were within the range of 0.03-0.1 s at different intensity levels for the mechanical group. The mechanothermal effect of FUS could induce both short-latency EMG (0.2-1.4 s) and long-latency EMG (8.7-13.0 s) under the same intensity levels as the mechanical group. The different temporal dynamics of evoked EMG suggested that FUS-induced mechanical and mechanothermal effects could evoke different responses in the brain.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects31, 8, 12swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutsemg mep, behaviour, other mri, histology molecular — tail EMG and tail movement; MR thermometry at 4.7 T; H&E, NeuN, GFAP and Iba1 staining
Direction of effectexcitatoryFUS evoked tail EMG and tail movements; 0.3 s sonications gave short-latency EMG, 15 s sonications (with heating) gave short- and long-latency EMG, with higher response rates at the same Isppa.
Adverse eventsnone observedHistology (H&E, NeuN, GFAP, Iba1) in 12 additional mice at 4.1-22.7 W/cm2 showed no tissue damage; MR thermometry measured temperature rise.

Exposures

Exposure 1: Deep cerebellar nucleus, mechanical (0.3 s) and mechanothermal (15 s) groups

Target: deep cerebellar nuclei — “cerebellar deep nuclei (DCN)”
Device: other named manufacturer · Wuxi Lanhui Electronic · TAPMM25 W ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)50✓✓✓⚑
Pulse repetition frequency (Hz)10✓✓✓
Duty cycle (%)50pulse duration × PRF gives 50%✓✓✓
Sonication duration (s)0.3, 15swept✓✓✓
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 estimatederatingsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)4.1, 7.8, 14, 22.7swept✓✓✓⚑
In-situ Ispta (W/cm²)2, 3.9, 7, 11.3swept✓✓✓⚑
Protocol, in the paper’s words

Mechanical group: 0.3 s sonications every 5 s, 10 repeats per intensity. Mechanothermal group: same pulsing but 15 s sonications with 80 s inter-stimulus interval, 5 repeats per intensity; intensity order randomised within each mouse.

Flags from extraction

  • n_subjects — Group sizes of separate experiments (31 behaviour/EMG, 8 MR thermometry, 12 safety); total not stated and overlap not stated.
  • exposures[0].in_situ.isppa_w_cm2 — Isppa calculated as P^2/2rho c with 14% skull attenuation (derating by authors); pressure values themselves not given.
  • exposures[0].in_situ.ispta_w_cm2 — Ispta values read from Table 1 ('Isppa/Ispta'); domain presumed same as Isppa.
  • exposures[0].timing.pulse_duration_ms — Text says 'pulse length = 50 ms'; with PRF 10 Hz and DC 50% this is consistent. Applies to both groups.
  • exposures[0].free_field.pressure_kpa — Field was calibrated in water with a hydrophone but no pressure values are stated in the text.