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

Abstract

BackgroundEpilepsy 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).ResultsAfter 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.ConclusionsThese 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.

Transcranial Focused Ultrasound to the Thalamus Is Associated with Reduced Extracellular GABA Levels in Rats

“…We have demonstrated that the pulsed application of low-intensity (i.e. lower than the intensity approved for diagnostic ultrasound imaging) focused ultrasound (FUS) on the rabbit brain modulated neural tissue excitability in a non-thermal manner [12] and reduced chemically induced epileptic states in rats [13] , all without inducing tissue/vascular damage. FUS is a technique that delivers acoustic energy to localized tissue areas (on the order of millimeters in diameter, roughly the size of a rice grain), thus allowing for the concurrent deposition of thermal or mechanical energy to a targeted tissue region [14][15][16] .…”

Application of High-Intensity Focused Ultrasound to the Study of Mild Traumatic Brain Injury

“…A similar and related application is acoustic neuromodulation, where, as part of treatment for a variety of neurologic disorders, ultrasound waves are used to control neuronal activity without producing heat or cavitation (Gavrilov et al 1996;Min et al 2011;Tufail et al 2010;Tyler et al 2008). In contrast to the therapeutic objective of acoustic neuromodulation, the intention of the present work was to induce mild injury in the brain.…”

High-intensity focused ultrasound: past, present, and future in neurosurgery

“…In a murine epilepsy model, MRgFUS has been shown to decrease epileptic activity that was induced by intraperitoneal injection of pentylenetetrazol. 63 Although further studies are warranted, neuromodulation with MRgFUS might provide clinicians with a future potential to noninvasively target a seizure focus in the brain before its permanent ablation, if needed.…”