Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain functionopen43

FUS-mediated Functional Neuromodulation for Neurophysiologic Assessment in a Large Animal Model

The goal of the proposed research is to investigate the method of using MR imageguided transcranial focused ultrasound (FUS) to reversibly modulate (i.e. elicit and suppress) the activity of a region-specific brain area in large animals (sheep). Electrophysiological representations resulting from the modulation will be assessed in terms of visual, somatosensory, and motor function. After the sonication, the safety profiles of the sonication will be examined through anatomical MRIs and histological analysis. The non-invasive neuromodulation of deep brain function and concurrent neurophysiologic assessment will be essential for mapping and confirmation of the treatment areas prior to FUS-mediated functional neurosurger

Pulsed application of focused ultrasound to the LI4 elicits deqi sensations: Pilot study

Objectives: Focused ultrasound (FUS) techniques enable the delivery of acoustic pressure waves to a localized, specific region of anatomy, and mechanically stimulate the sonicated region when given in a train of pulses. The present pilot study examines if the pulsed application of acoustic waves focused to an acupuncture point ( LI4, Hegu), i.e. FUS acupuncture, can elicit deqi sensations. Design and setting: The FUS was generated by a single-element ultrasound transducer, and delivered to the LI4 of acupuncture-naive participants (n =10) for a duration of 1s using 2ms tone-burst-duration and 50Hz pulse repetition frequency. The subjective ratings of deqi descriptors were obtained across different conditions, i.e. FUS acupuncture using acoustic intensities of 1 and 3W/cm2 (spatial-peak temporal-averaged intensity, I spta), sham sonication condition, tactile stimulation using a von Frey monofilament, and needle-based real and sham acupuncture. We also measured the presence of sharp pain, unpleasantness, and anxiety level during each condition. Results: The FUS acupuncture given at 3W/cm2 elicited deqi sensation ratings similar to those acquired during the needle-based acupuncture condition across the subjects, with significantly reduced levels of non-deqi related sensations, such as sharp pain, anxiety and unpleasantness. The lower acoustic intensity also generated deqi sensations, but at a lesser degree than the ones acquired using the higher acoustic intensity. Neither the sham conditions nor the tactile stimulation elicited deqi sensations. Conclusions: The present data on acoustic acupuncture, with its exquisite spatial and depth control, along with the ability to electronically adjust its intensity, may suggest its potential utilization as an alternative mode of acupuncture, although further study is needed to probe its clinical efficacy.close0

Isomagnetophoresis for discrimination of magnetic susceptibility and its application to continuous separation

We report an improved magnetophoretic method, isomagnetophoresis, employing the magnetic susceptibility gradient across a microfluidic channel applied by magnetic field, and we have successfully discriminated the polystyrene (PS; 14.78 ?? 0.20 ??m in diameter), poly(methyl methacrylate) (PMMA; 15.00 ?? 0.77 ??m) and borosilicate (BS; 14.01 ?? 1.00 ??m) microspheres, where PS and PMMA particles have similar diamagnetic susceptibility that cannot be distinguished by conventional magnetophoresis. This platform can be applied to label-free discrimination of the biological cells and nanotubes.clos

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

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

Non-invasive transmission of sensorimotor information in humans using an EEG/focused ultrasound brain-to-brain interface

We present non-invasive means that detect unilateral hand motor brain activity from one individual and subsequently stimulate the somatosensory area of another individual, thus, enabling the remote hemispheric link between each brain hemisphere in humans. Healthy participants were paired as a sender and a receiver. A sender performed a motor imagery task of either right or left hand, and associated changes in the electroencephalogram (EEG) mu rhythm (8–10 Hz) originating from either hemisphere were programmed to move a computer cursor to a target that appeared in either left or right of the computer screen. When the cursor reaches its target, the outcome was transmitted to another computer over the internet, and actuated the focused ultrasound (FUS) devices that selectively and non-invasively stimulated either the right or left hand somatosensory area of the receiver. Small FUS transducers effectively allowed for the independent administration of stimulatory ultrasonic waves to somatosensory areas. The stimulation elicited unilateral tactile sensation of the hand from the receiver, thus establishing the hemispheric brain-to-brain interface (BBI). Although there was a degree of variability in task accuracy, six pairs of volunteers performed the BBI task in high accuracy, transferring approximately eight commands per minute. Linkage between the hemispheric brain activities among individuals suggests the possibility for expansion of the information bandwidth in the context of BBI

Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound

Background: Transcranial focused ultrasound (FUS) is gaining momentum as a novel non-invasive brain stimulation method, with promising potential for superior spatial resolution and depth penetration compared to transcranial magnetic stimulation or transcranial direct current stimulation. We examined the presence of tactile sensations elicited by FUS stimulation of two separate brain regions in humans—the primary (SI) and secondary (SII) somatosensory areas of the hand, as guided by individual-specific functional magnetic resonance imaging data. Results: Under image-guidance, acoustic stimulations were delivered to the SI and SII areas either separately or simultaneously. The SII areas were divided into sub-regions that are activated by four types of external tactile sensations to the palmar side of the right hand—vibrotactile, pressure, warmth, and coolness. Across the stimulation conditions (SI only, SII only, SI and SII simultaneously), participants reported various types of tactile sensations that arose from the hand contralateral to the stimulation, such as the palm/back of the hand or as single/neighboring fingers. The type of tactile sensations did not match the sensations that are associated with specific sub-regions in the SII. The neuro-stimulatory effects of FUS were transient and reversible, and the procedure did not cause any adverse changes or discomforts in the subject’s mental/physical status. Conclusions: The use of multiple FUS transducers allowed for simultaneous stimulation of the SI/SII in the same hemisphere and elicited various tactile sensations in the absence of any external sensory stimuli. Stimulation of the SII area alone could also induce perception of tactile sensations. The ability to stimulate multiple brain areas in a spatially restricted fashion can be used to study causal relationships between regional brain activities and their cognitive/behavioral outcomes. Electronic supplementary material The online version of this article (doi:10.1186/s12868-016-0303-6) contains supplementary material, which is available to authorized users

EAP-FUS022 (Yoo): FUS Mediated Reversible Modulation of Region Specific Brain Function

The goal of the proposed research is to investigate the feasibility of using low-intensity and lowfrequency focused ultrasound energy to reversibly modulate the activity of a region-specific brain area. We will modulate the cortical activity from an animal brain using FUS sonication, as monitored by real-time functional MRI. Prior to the animal experiment, in-vitro phantoms containing neural cells will be constructed and sonicated to estimate the range of suitable sonication parameters. This work is expected to provide an unprecedented opportunity for the transient functional modulation of targeted brain regions, creating a new line of applications, such as FUS-mediated functional mapping