Noninvasive transcranial stimulation of rat abducens nerve by focused ultrasound.
Authors: Kim H, Taghados SJ, Fischer K, Maeng LS, Park S, Yoo SS
Nonpharmacologic and nonsurgical transcranial modulation of the nerve function may provide new opportunities in evaluation and treatment of cranial nerve diseases. This study investigates the possibility of using low-intensity transcranial focused ultrasound (FUS) to selectively stimulate the rat abducens nerve located above the base of the skull. FUS (frequencies of 350 kHz and 650 kHz) operating in a pulsed mode was applied to the abducens nerve of Sprague-Dawley rats under stereotactic guidance. The abductive eyeball movement ipsilateral to the side of sonication was observed at 350 kHz, using the 0.36-msec tone burst duration (TBD), 1.5-kHz pulse repetition frequency (PRF), and the overall sonication duration of 200 msec. Histologic and behavioral monitoring showed no signs of disruption in the blood brain barrier (BBB), as well as no damage to the nerves and adjacent brain tissue resulting from the sonication. As a novel functional neuro-modulatory modality, the pulsed application of FUS has potential for diagnostic and therapeutic applications in diseases of the peripheral nervous system.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
To investigate whether low-intensity transcranial pulsed focused ultrasound can selectively stimulate the rat abducens nerve noninvasively without causing tissue damage.
Animal model / Human subject
Sprague-Dawley rat (Rattus norvegicus), age not specified, sex not specified
Disease model
Healthy
MRI or image guidance method
Stereotactic guidance
Targeted brain region(s)
abducens nerve
Outcomes and Safety
Summary of Outcomes
Pulsed low‑intensity transcranial focused ultrasound selectively stimulated the rat abducens nerve, producing ipsilateral abductive eyeball movements without detectable BBB disruption or tissue damage. Successful parameters: 350 kHz carrier frequency, 0.36 ms tone‑burst duration, 1.5 kHz pulse repetition frequency, 200 ms overall sonication duration (650 kHz was tested but did not elicit the reported effect).
Duration of biological effect
200 msec
Safety-related matter
Histological and behavioral monitoring showed no disruption of the blood–brain barrier and no damage to the abducens nerve or adjacent brain tissue from the focused ultrasound sonication, i.e., no adverse effects were found.
Brain Region
Ultrasound Parameters
FUS Frequency
350 kHz, 650 kHz
FUS Mode
pulsed
Pulse duration
0.36 ms
Duration of a single FUS session
200 msec
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
single session
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