Dataset Information

Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model.

ABSTRACT: Low-intensity focused ultrasound (FUS) has significant potential as a non-invasive brain stimulation modality and novel technique for functional brain mapping, particularly with its advantage of greater spatial selectivity and depth penetration compared to existing non-invasive brain stimulation techniques. As previous studies, primarily carried out in small animals, have demonstrated that sonication parameters affect the stimulation efficiency, further investigation in large animals is necessary to translate this technique into clinical practice. In the present study, we examined the effects of sonication parameters on the transient modification of excitability of cortical and thalamic areas in an ovine model. Guided by anatomical and functional neuroimaging data specific to each animal, 250 kHz FUS was transcranially applied to the primary sensorimotor area associated with the right hind limb and its thalamic projection in sheep (n = 10) across multiple sessions using various combinations of sonication parameters. The degree of effect from FUS was assessed through electrophysiological responses, through analysis of electromyogram and electroencephalographic somatosensory evoked potentials for evaluation of excitatory and suppressive effects, respectively. We found that the modulatory effects were transient and reversible, with specific sonication parameters outperforming others in modulating regional brain activity. Magnetic resonance imaging and histological analysis conducted at different time points after the final sonication session, as well as behavioral observations, showed that repeated exposure to FUS did not damage the underlying brain tissue. Our results suggest that FUS-mediated, non-invasive, region-specific bimodal neuromodulation can be safely achieved in an ovine model, indicating its potential for translation into human studies.

SUBMITTER: Yoon K

PROVIDER: S-EPMC6812789 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model.

Yoon Kyungho K Lee Wonhye W Lee Ji Eun JE Xu Linda L Croce Phillip P Foley Lori L Yoo Seung-Schik SS

PloS one 20191024 10

Low-intensity focused ultrasound (FUS) has significant potential as a non-invasive brain stimulation modality and novel technique for functional brain mapping, particularly with its advantage of greater spatial selectivity and depth penetration compared to existing non-invasive brain stimulation techniques. As previous studies, primarily carried out in small animals, have demonstrated that sonication parameters affect the stimulation efficiency, further investigation in large animals is necessar ...[more]

PMID: 31648261

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Project description:Focused ultrasound is a promising therapeutic technique, as it involves the focusing of an ultrasonic beam with sufficient acoustic energy into a target brain region with high precision. Low-intensity ultrasound transmission by a single-element transducer is mostly established for neuromodulation applications and blood-brain barrier disruption for drug delivery. However, transducer positioning errors can occur without fine control over the sonication, which can affect repeatability and lead to reliability problems. The objective of this study was to determine whether the target brain region would be stable under small displacement (0.5 mm) of the transducer based on numerical simulations. Computed-tomography-derived three-dimensional models of a rat head were constructed to investigate the effects of transducer displacement in the caudate putamen (CP) and thalamus (TH). Using three different frequencies (1.1, 0.69, and 0.25 MHz), the transducer was displaced by 0.5 mm in each of the following six directions: superior, interior, anterior, posterior, left, and right. The maximum value of the intracranial pressure field was calculated, and the targeting errors were determined by the full-width-at-half-maximum (FWHM) overlap between the free water space (FWHMwater) and transcranial transmission (FWHMbase). When the transducer was positioned directly above the target region, a clear distinction between the target regions was observed, resulting in 88.3%, 81.5%, and 84.5% FWHMwater for the CP and 65.6%, 76.3%, and 64.4% FWHMwater for the TH at 1.1, 0.69, and 0.25 MHz, respectively. Small transducer displacements induced both enhancement and reduction of the peak pressure and targeting errors, compared with when the transducer was displaced in water. Small transducer displacement to the left resulted in the lowest stability, with 34.8% and 55.0% targeting accuracy (FWHMwater) at 1.1 and 0.69 MHz in the TH, respectively. In addition, the maximum pressure was reduced by up to 11% by the transducer displacement. This work provides the targeting errors induced by transducer displacements through a preclinical study and recommends that attention be paid to determining the initial sonication foci in the transverse plane in the cases of small animals.

Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has emerged as a new non-invasive modality of brain stimulation with the potential for high spatial selectivity and penetration depth. Anesthesia is typically applied in animal-based tFUS brain stimulation models; however, the type and depth of anesthesia are known to introduce variability in responsiveness to the stimulation. Therefore, the ability to conduct sonication experiments on awake small animals, such as rats, is warranted to avoid confounding effects of anesthesia.ResultsWe developed a miniature tFUS headgear, operating at 600 kHz, which can be attached to the skull of Sprague-Dawley rats through an implanted pedestal, allowing the ultrasound to be transcranially delivered to motor cortical areas of unanesthetized freely-moving rats. Video recordings were obtained to monitor physical responses from the rat during acoustic brain stimulation. The stimulation elicited body movements from various areas, such as the tail, limbs, and whiskers. Movement of the head, including chewing behavior, was also observed. When compared to the light ketamine/xylazine and isoflurane anesthetic conditions, the response rate increased while the latency to stimulation decreased in the awake condition. The individual variability in response rates was smaller during the awake condition compared to the anesthetic conditions. Our analysis of latency distribution of responses also suggested possible presence of acoustic startle responses mixed with stimulation-related physical movement. Post-tFUS monitoring of animal behaviors and histological analysis performed on the brain did not reveal any abnormalities after the repeated tFUS sessions.ConclusionsThe wearable miniature tFUS configuration allowed for the stimulation of motor cortical areas in rats and elicited sonication-related movements under both awake and anesthetized conditions. The awake condition yielded diverse physical responses compared to those reported in existing literatures. The ability to conduct an experiment in freely-moving awake animals can be gainfully used to investigate the effects of acoustic neuromodulation free from the confounding effects of anesthesia, thus, may serve as a translational platform to large animals and humans.

Dataset Information

Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model.

Publications

Effects of sonication parameters on transcranial focused ultrasound brain stimulation in an ovine model.

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