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Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters.

Authors: Kim H, Chiu A, Lee SD, Fischer K, Yoo SS

Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation. The objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague-Dawley rats. We transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency. We observed that motor responses were elicited at minimum threshold acoustic intensities (4.9-5.6 W/cm(2) in spatial-peak pulse-average intensity; 2.5-2.8 W/cm(2) in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1-5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication. Our results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine the range of transcranial focused ultrasound sonication parameters that minimize acoustic intensity/energy deposition while effectively stimulating the motor cortex in Sprague-Dawley rats.
Animal model / Human subject rats, Sprague-Dawley, not specified, not specified
Disease model healthy
Targeted brain region(s) Motor Cortex

Outcomes and Safety

Summary of Outcomes Pulsed transcranial FUS at 350 kHz elicited motor responses in rats at minimal thresholds (SPPA 4.9–5.6 W/cm2; SPTA 2.5–2.8 W/cm2), with successful sonication parameters being 1–5 ms tone‑burst duration, 50% duty cycle, 300 ms sonication duration, and pulsed protocols requiring lower intensity than equivalent continuous sonication.
Duration of biological effect not reported
Safety-related matter No adverse effects reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument single-element focused ultrasound transducer
FUS Frequency 350 kHz
FUS Intensity Spatial-peak pulse-average: 4.9-5.6 W/cm2; Spatial-peak temporal-average: 2.5-2.8 W/cm2
FUS Pressure not reported
FUS Mode pulsed
Pulse duration 1-5 ms
Duration of a single FUS session 300 ms
Treatment frequency Multiple sessions

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