Hyungmin Kim

Michael Y Park

Seung-Schik Yoo

Stephanie D Lee

Wonhye Lee

Journal of Therapeutic Ultrasound

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ORAL PRESENTATION Open Access
FUS-mediated functional neuromodulation for
neurophysiologic assessment in a large animal
model
Wonhye Lee1*, Hyungmin Kim2, Stephanie D. Lee1, Michael Y. Park1, Seung-Schik Yoo1
From Current and Future Applications of Focused Ultrasound 2014. 4th International Symposium
Washington, D.C, USA. 12-16 October 2014
Background/introduction
Focused ultrasound (FUS) is gaining momentum as a
new modality of non-invasive neuromodulation of regio-
nal brain activity, with both stimulatory and suppressive
potentials. The utilization of the method has largely
been demonstrated in small animals. Considering the
small size of the acoustic focus, having a diameter of
only a few millimeters, FUS insonification to a larger
animal’s brain is conducive to examining the region-
specific neuromodulatory effects on discrete anatomical
areas, including the white matter (WM) tracts. The
study involving large animals would also establish preli-
minary safety data prior to its translational research in
humans.
Methods
Sheep (all female, 25–40 kg, n = 8) were chosen for the
transcranial application of FUS due to their round cra-
nium and skull thickness (4–5 mm) that was close to
that of humans. All procedures were approved by the
local Institutional Animal Care and Use Committee, and
done under the intravenous Tiletamine anesthesia. To
provide the information for positioning of the FUS focus
to the individual functional neuroanatomy, sheep’s brain
was imaged using a 3T MRI scanner (GE VH, Wauke-
sha, WI) using anatomical (both T1- and T2-weighted)
and functional MR protocols (fMRI, T2*-weighted). The
somatosensory and visual areas of the sheep brain were
mapped while using sensorimotor (i.e. gentle 2 Hz
squeeze of the right hind leg muscle) and visual (i.e.
2 Hz strobe lights to both eyes) stimuli. As guided by
these neuroimage data, the sonication (250 kHz, single-
element FUS transducer with radius-of-curvature of
7 cm) was transcranially delivered to the unilateral sen-
sorimotor cortex, the optic radiation (WM tract) as well as
the visual cortex. An acoustic intensity of 1.4–15.5 W/cm2
Isppa, tone-burst-duration of 1 ms, pulse-repetition fre-
quency of 500 Hz (i.e. duty cycle of 50%), sonication dura-
tion of 300 ms, were used for the stimulation. A batch of
continuous sonication ranging from 50 to 150 ms in dura-
tion were also given. Evoked electromyogram responses
from the hind legs and electroencephalogram from the Fz
and Oz-equivalent sites were measured. The histology of
the extracted brain tissue (within one week and 2 months
post-sonication) was obtained.
Results and conclusions
The acoustic transmission measured through the extracted
skulls (n = 8) was 41.5% of incident intensity. We detected
a motor evoked potential (EP) from the hind leg muscle
contralateral to the sonicated hemisphere above 6.9 W/
cm2 Isppa (i.e. 3.5 W/cm2 Ispta), which served as a thresh-
old intensity. The stimulation was not accompanied by the
actual muscle movement. The amplitude of EP was greater
than the one obtained using the lower acoustic intensity.
Similarly, FUS-mediated visual EP was also detected at a
similar threshold level without the presence of external
lights. Continuous sonication also elicited stimulatory
responses, suggesting that continuous short bursts of the
FUS can also stimulate the brain. On the other hand, no
response was detected from the sonication of the optic
radiation, which indicates that FUS may not stimulate the
WM tracts. The sheep’s health status was normal through-
out all the sonication experiments. Histological analysis of
the extracted brain showed no apparent biological damages.
The transcranial FUS may serve as a novel tool to transi-
ently and reversibly modulate regional brain functions,
1Brigham & Women’s Hospital, Boston, MA, United States
Full list of author information is available at the end of the article
Lee et al. Journal of Therapeutic Ultrasound 2015, 3(Suppl 1):O23
http://www.jtultrasound.com/content/3/S1/O23
© 2015 Lee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://
creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
which will enable electrophysiological assessments on the
function of an ablative target prior to FUS-mediated
neurosurgery.
Acknowledgements (Funding)
This study was supported by the Focused Ultrasound Foundation.
Authors’ details
1Brigham & Women’s Hospital, Boston, MA, United States. 2Korea Institute of
Science and Technology, Seoul, Republic of Korea.
Published: 30 June 2015
doi:10.1186/2050-5736-3-S1-O23
Cite this article as: Lee et al.: FUS-mediated functional neuromodulation
for neurophysiologic assessment in a large animal model. Journal of
Therapeutic Ultrasound 2015 3(Suppl 1):O23.
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FUS-mediated functional neuromodulation for neurophysiologic assessment in a large animal model

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FUS-mediated functional neuromodulation for neurophysiologic assessment in a large animal model

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