A Review of Low-Intensity Transcranial Focused Ultrasound for Clinical Applications

Bystritsky, Alexander; Korb, Alexander

doi:10.1007/s40473-015-0039-0

Cited by 53 publications

(38 citation statements)

References 32 publications

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“…[2,13,24,27] The likely basis are mechanical effects on cell membranes affecting mechanosensitive ion channels and generating membrane pores. Several principles, related to different ultrasound-based techniques, have been proposed.…”

Section: Discussionmentioning

confidence: 99%

“…[10] Initial clinical data concerning nontargeted stimulation and a case report are also available. It consists of a mobile single transducer system which avoids long sonication trains, [2,13] and therefore the risks of secondary stimulation maxima or brain heating can be avoided. It consists of a mobile single transducer system which avoids long sonication trains, [2,13] and therefore the risks of secondary stimulation maxima or brain heating can be avoided.…”

Section: Introductionmentioning

confidence: 99%

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Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy

et al. 2019

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Ultrasound‐based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham‐controlled clinical studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy

et al. 2019

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“…By using ultrasound waves (≥ 20 kHz) to penetrate the skull and target brain tissue in a focused way, low-intensity transcranial focused ultrasound (tFUS) has demonstrated its unprecedented capability in non-invasive neural stimulation [1,2], and unparalleled prospects for translational clinical application [3]. Different from high-intensity focused ultrasound (HIFU) [4], low-intensity tFUS can achieve reversible neural effects while complying with the Food and Drug Administration’s (FDA) [5] safety requirements, thus ensuring safety of human subjects.…”

Section: Introductionmentioning

confidence: 99%

On the neuromodulatory pathways of the in vivo brain by means of transcranial focused ultrasound

Niu

2018

Current Opinion in Biomedical Engineering

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For last decade, low-intensity transcranial focused ultrasound (tFUS) has been rapidly developed for a myriad of successful applications in neuromodulation. tFUS possesses high spatial resolution, focality and depth penetration as a noninvasive neuromodulation tool. Despite the promise, confounding activation can be observed in rodents when stimulation parameters are not selected carefully. Here we summarize the existing classes of observations for ultrasound neuromodulation: ultrasound directly activates a localized area, or ultrasound indirectly activates auditory pathways, which further propagates to other cortical networks. We also present control in vivo animal studies, which suggest that underlying tFUS brain modulation is characterized by localized activation independent of auditory networks activations.

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“…Our study revealed that US is able to activate A1 with spatial-peak pulse-average acoustic intensities (ISPPA) 302 as low as 20 mW/cm 2 (~25 kPa for the 0.22 MHz transducer), which are lower than what has been 303 previously published for brain activation (Bystritsky and Korb, 2015;Bystritsky et al, 2011;Tufail et al, 304 2010). However, this US-evoked A1 activity is through a non-direct cochlear fluid pathway rather than 305 direct activation of A1 neurons.…”

mentioning

confidence: 50%

Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway

Guo

Hamilton

Offutt

et al. 2017

Preprint

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SummaryUltrasound (US) can noninvasively activate intact brain circuits, making it a promising neuromodulation technique. However, little is known about the underlying mechanism. Here, we apply transcranial US and perform brain mapping studies in guinea pigs using extracellular electrophysiology. We find that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminates the US-induced activity, revealing an indirect auditory mechanism for US neural activation. US likely vibrates the cerebrospinal fluid in the brain, which is continuous with the fluid in the cochlea via cochlear aqueducts; thus, US can activate the ascending auditory pathways and other non-auditory regions through cross-modal projections. This finding of a cochlear fluidinduced vibration mechanism challenges the idea that US can directly activate neurons in the intact brain, suggesting that future US stimulation studies will need to control for this effect to reach reliable conclusions.peer-reviewed)

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A Review of Low-Intensity Transcranial Focused Ultrasound for Clinical Applications

Cited by 53 publications

References 32 publications

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy

Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease—A New Navigated Focal Brain Therapy

On the neuromodulatory pathways of the in vivo brain by means of transcranial focused ultrasound

Ultrasound Produces Extensive Brain Activation via a Cochlear Pathway

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