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Neuroscientists Produce Guide For Using Ultrasound To Treat Brain Disorders In Clinical Emergencies

The discovery that low-intensity, pulsed ultrasound can be used to noninvasively
stimulate intact brain circuits holds promise for engineering rapid-response
medical devices. The team that made that discovery, led by William “Jamie”
Tyler, an assistant professor with the Virginia Tech Carilion Research
Institute, has now produced an in-depth article detailing this approach, which
may one day lead to first-line therapies in combating life-threatening epileptic
seizures.
Status epilepticus is a condition in which the brain is in a
state of persistent seizure and which, if not halted, can lead to Sudden
Unexplained Death in Epilepsy (SUDEP). But, as the recent article by Tyler and
colleagues shows, ultrasonic neuromodulation does not necessarily need to be
focused to attenuate epileptic seizures, meaning that it can be quickly applied
in neurocritical care situations.

“Imagine a device like an automatic
external defibrillator except for the brain,” said first author Yusuf Tufail,
who is now a postdoctoral associate at the Salk Institute for Biological
Sciences.

Published in the September issue of “Nature Protocols,” the
article, “Ultrasonic Neuromodulation by Brain Stimulation with Transcranial
Ultrasound,” provides a guide for the further development and clinical
application of ultrasonic neuromodulation. The authors Yusuf Tufail, Anna
Yoshihiro, and Monica M. Li of Arizona State University’s School of Life
Sciences; Sandipan Pati of Barrow Neurological Institute at St. Joseph’s
Hospital and Medical Center in Phoenix, Ariz.; and corresponding author Tyler
also published their earlier research into the feasibility of this approach in
“Neuron” in 2010.

Ultrasound is an acoustic wave occurring at frequencies
exceeding the range of human hearing. Uses range from food processing to
communication and include medical imaging. Tyler and his research group have
spent several years developing noninvasive methods for brain stimulation
employing low-intensity, low-frequency (LILFU) ultrasound. “Much of our time had
been spent on understanding the biological effects of LILFU on intact brain
circuits and how to control neural activity using LILFU,” Tyler said.

The
team has observed that the mechanical bioeffects of ultrasound are indeed
capable of stimulating neuronal activity, meaning that ultrasound could join
other therapies for neurological disorders namely, implanted electrodes, such as
those used in deep-brain stimulation, and external magnetic stimulators used for
transcranial magnetic stimulation to treat disorders such as Parkinson’s disease, major depression, and dystonia. The major advantage of using
ultrasound for brain stimulation is that it can confer spatial resolution at
millimeter precision while being focused through the skull to deep-brain regions
without the need for invasive brain surgery, Tyler said.

“We have also
shown that ultrasound can be used to stimulate synaptic transmission between
groups of neurons within the brain in a manner similar to conventional implanted
stimulating electrodes without generating significant heating of the brain
tissue,” said Tyler.

“Further studies are required to fully elucidate the
many potential mechanisms underlying the ability of ultrasound to stimulate
neuronal activity in the intact brain,” the article states. However, while using
ultrasound for brain stimulation represents a powerful new tool for clinical
neuroscience, there are potential concerns, since high-intensity ultrasound is
also capable of destroying biological tissues, the researchers write.

The
article reports that ultrasound has been used for many hours across many weeks,
“stimulating cellular circuits in the living brain without producing damage in
mice as assessed with cellular, histological, ultrastructural, and behavioral
methods.” The researchers added a note of caution: “Additional investigations
across animal species and dosage levels are required, however, before the safety
can be fully ascertained.”

Moving this technology forward will require
scientists, engineers, and physicians spanning many disciplines. The impetus for
the “Nature Protocols” article is to disseminate basic methods for conducting
ultrasonic neuromodulation. “There is a major need for increased open
communication among engineers designing ultrasound-based medical devices,
neuroscientists studying the core biological effects of ultrasound, and
clinicians implementing ultrasound for therapeutic interventions,” said
Tyler.

The “Nature Protocols” article poses specific questions needing to
be addressed, such as how ultrasound affects neurons on a molecular and cellular
level, how to correct for impedance mismatches between skin and skull
interfaces, and the need for characterizing safety across different exposure
times, applications, and disease states.

The research reported in the
article provides the provocative demonstration that ultrasonic neuromodulation
is capable of attenuating seizure activity during pharmacologically induced
status epilepticus in rodents. “While other research groups have reported that
focused ultrasound can modulate seizure activity in the brain, the approaches
used in those earlier studies require timely preparations and the implementation
of MRI to focus the ultrasound in an approach known as magnetic resonance-guided
focused ultrasound,” said Tyler. “Our findings show that clinicians may not need
to take such complicated, costly, and time-consuming approaches to treating
patients in critical situations.”

Sources: Virginia Tech/ Medical News Today

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