Noninvasive Transcranial Stimulation of Rat Abducens Nerve by Focused Ultrasound

Abstract

Non-pharmacological and non-surgical 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. Histological 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 in diagnostic and therapeutic applications in diseases of the peripheral nervous system.

Focused Low-Intensity Pulsed Ultrasound Enhances Bone Regeneration in Rat Calvarial Bone Defect through Enhancement of Cell Proliferation

“…To date, the focused LIPUS technique has been investigated to determine if it has the potential for non-invasive neuromodulation and modulation of region-specific brain activity. Specifically, Kim et al (2012) investigated the possibility of using focused LIPUS at 350 and 650 kHz to selectively stimulate the rat abducens nerve located above the base of the skull. In addition, Yoo et al (2011) reported that neuromodulation by focused LIPUS is involved in cellular excitability through regulation of ion channels and mechanoreceptors embedded within the membrane.…”

First Non-invasive Thermal Ablation of a Brain Tumor with MR Guided Focused Ultrasound

“…Beyond thermal ablation, HIFU has notably been shown to allow safe, nondestructive, and transient focal blood-brain barrier disruption to facilitate drug delivery [24,25] and is being evaluated as a tool to induce hyperthermia to enhance the therapeutic effect of radiotherapy and chemotherapy [26][27][28]. Transcranial noninvasive HIFU has also been used to modulate cortex activity in a study with human volunteers [29] and to stimulate deep brain nuclei [30]. This makes HIFU potentially capable of combining lower ultrasound intensities for tissue stimulation monitoring before the application of higher intensities for ablation.…”

The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine

“…It has been hypothesized that continuous-wave US can be more damaging to certain tissues as compared to pulsed-wave US, potentially due to rapid heating due to friction [Ziskin, 1993]. Currently, there is no clear indication of which technique may be more efficacious for NM, though it is likely that it is target specific, and further complicated by the depth of a tissue structure, the homogeneity of intervening tissue before the target, and the prevalence of mechanosensitive elements of the target cell type itself [Kim et al, 2012]. With regard to neural tissues specifically, both continuous-wave and pulsed-wave US have been found to be effective in modulating neural activity [King et al, 2013].…”