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

Authors: Baek H, Yang Y, Pacia CP, Xu L, Yue Y, Bruchas MR, Chen H

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<i>in vivo</i>. 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.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective Compare motor responses induced by focused ultrasound (FUS) neuromodulation under mechanical versus mechanothermal mechanisms.
Animal model / Human subject mouse, C57BL/6, adult, male
Disease model healthy
MRI or image guidance method MR thermometry used for in vivo temperature monitoring; targeting based on mouse brain atlas coordinates (stereotactic alignment)
Targeted brain region(s) Dcn
Target coordinates Not provided

Outcomes and Safety

Summary of Outcomes Both short-duration (mechanical) and long-duration (mechanothermal) focused ultrasound targeted to the deep cerebellar nucleus evoked motor responses, with mechanical stimulation producing rapid EMG latencies (0.03–0.1 s) while mechanothermal stimulation produced measurable brain heating (up to ~3.3°C) and both short- (0.2–1.4 s) and long-latency (8.7–13.0 s) EMG responses.
Duration of biological effect 15 s
Safety-related matter No adverse effects were reported; mechanothermal FUS produced measurable brain heating (0.6 ± 0.2°C–3.3 ± 0.9°C) and heating along the beam path, whereas mechanical FUS produced negligible temperature rise (0.2 ± 0.1°C).

Brain Region

Ultrasound Parameters

Ultrasound instrument VANTAGE, Verasonics; FUSX-A010-S, Sonic Concepts
FUS Frequency 1.5 MHz
FUS Intensity 4.1–22.7 W/cm² (Isppa)
FUS Pressure 0.82 Mpa
FUS Mode pulsed
Pulse duration 0.5 ms
Duration of a single FUS session 0.3 s (short-duration, mechanical) or 15 s (long-duration, mechanothermal)
Focal Characteristics Not specified
Treatment frequency single session

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