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Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity.

Authors: Min BK, Bystritsky A, Jung KI, Fischer K, Zhang Y, Maeng LS, Park SI, Chung YA, Jolesz FA, Yoo SS

Epilepsy is a common neurological disorder, which is attributed to uncontrollable abnormal hyper-excitability of neurons. We investigated the feasibility of using low-intensity, pulsed radiation of focused ultrasound (FUS) to non-invasively suppress epileptic activity in an animal model (rat), which was induced by the intraperitonial injection of pentylenetetrazol (PTZ). After the onset of induced seizures, FUS was transcranially administered to the brain twice for three minutes each while undergoing electroencephalographic (EEG) monitoring. An air-backed, spherical segment ultrasound transducer (diameter: 6 cm; radius-of-curvature: 7 cm) operating at a fundamental frequency of 690 KHz was used to deliver a train of 0.5 msec-long pulses of sonication at a repetitive rate of 100 Hz to the thalamic areas of the brain. The acoustic intensity (130 mW/cm2) used in the experiment was sufficiently within the range of safety guidelines for the clinical ultrasound imaging. The occurrence of epileptic EEG bursts from epilepsy-induced rats significantly decreased after sonication when it was compared to the pre-sonication epileptic state. The PTZ-induced control group that did not receive any sonication showed a sustained number of epileptic EEG signal bursts. The animals that underwent sonication also showed less severe epileptic behavior, as assessed by the Racine score. Histological analysis confirmed that the sonication did not cause any damage to the brain tissue. These results revealed that low-intensity, pulsed FUS sonication suppressed the number of epileptic signal bursts using acute epilepsy model in animal. Due to its non-invasiveness and spatial selectivity, FUS may offer new perspectives for a possible non-invasive treatment of epilepsy.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To investigate whether low-intensity, pulsed focused ultrasound (FUS) can noninvasively suppress epileptic activity in a pentylenetetrazol-induced rat model.
Animal model / Human subject rat, Sprague-Dawley, not reported, male
Disease model epilepsy
MRI or image guidance method Stereotactic coordinates (small-animal stereotaxic frame/3-axis positioning system); target = thalamus (~5 mm deep, midline, 2 mm posterior to bregma)
Targeted brain region(s) Thalamus
Target coordinates AP: -2 mm (posterior to bregma), ML: 0 mm (midline), DV: 5 mm (depth from surface)

Outcomes and Safety

Summary of Outcomes Pulsed FUS to the thalamus significantly reduced PTZ-induced epileptic EEG bursts and behavioral seizure severity.
Duration of biological effect 1 day
Safety-related matter No detectable brain tissue damage or DNA fragmentation observed at tested intensities.

Brain Region

Ultrasound Parameters

Ultrasound instrument single-element focused ultrasound transducer
FUS Frequency 690 kHz
FUS Intensity 0.13 W/cm^2 (130 mW/cm^2, I_spta); 2.6 W/cm^2 (I_sppa)
FUS Pressure 0.27 MPa
FUS Mode pulsed
Pulse duration 0.5 ms
Duration of a single FUS session 6 minutes
Focal Characteristics 5 mm
Treatment frequency single
Mechanical index 0.3250418033315769

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