A Review of Low-Intensity Transcranial Focused Ultrasound for Clinical Applications (original) (raw)
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Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound
PLoS ONE, 2014
Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250-700 kHz) ultrasound with spatial peak temporal average intensities (I SPTA ) of 0.1-10 W/cm 2 . That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, 'modulated' means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU's ability to produce compact sources of ultrasound at the very low frequencies (10-100s of Hertz) that are commensurate with the natural frequencies of the brain. Citation: Mehić E, Xu JM, Caler CJ, Coulson NK, Moritz CT, et al. (2014) Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound. PLoS ONE 9(2): e86939.
Focused Ultrasound for Neuromodulation
Neurotherapeutics
For more than 70 years, the promise of noninvasive neuromodulation using focused ultrasound has been growing while diagnostic ultrasound established itself as a foundation of clinical imaging. Significant technical challenges have been overcome to allow transcranial focused ultrasound to deliver spatially restricted energy into the nervous system at a wide range of intensities. High-intensity focused ultrasound produces reliable permanent lesions within the brain, and low-intensity focused ultrasound has been reported to both excite and inhibit neural activity reversibly. Despite intense interest in this promising new platform for noninvasive, highly focused neuromodulation, the underlying mechanism remains elusive, though recent studies provide further insight. Despite the barriers, the potential of focused ultrasound to deliver a range of permanent and reversible neuromodulation with seamless translation from bench to the bedside warrants unparalleled attention and scientific investment. Focused ultrasound boasts a number of key features such as multimodal compatibility, submillimeter steerable focusing, multifocal, high temporal resolution, coregistration, and the ability to monitor delivered therapy and temperatures in real time. Despite the technical complexity, the future of noninvasive focused ultrasound for neuromodulation as a neuroscience and clinical platform remains bright.
Focused Ultrasound-mediated Acoustic Neuromodulation
Ultrasound in Medicine & Biology, 2015
A new method of non-invasive brain stimulation utilizing low intensity focused ultrasound (FUS) is introduced. The exquisite ability to deliver acoustic energy to the region-specific brain area with excellent depth penetration endowed by FUS was applied for the implementation and demonstration of the method. The pulsed application of FUS to the regional brain area has showed bimodal effects (i.e. both excitatory and suppressive) on the central nervous system, along with the ability to stimulate the cranial nerves (abducens nerve for oculomotor function). Pulsing strategy and key evidences for acoustic neuromodulation were obtained through small animal model studies (rats and rabbits). FUS-mediated brain stimulation induced corresponding physical representation (i.e. body movement), appropriate electrophysiological responses, functional imaging findings (both via functional MRI and via fluorodeoxyglucose positron emission tomography), and changes in the extracellular level of neurotransmitters. Experimental data from a large animal (sheep) model on visual and motor area stimulation will be presented, along with the preliminary data obtained from applying transcranial FUS to human primary somatosensory areas. With further investigation, the method may provide powerful treatment and diagnostic options for various neurological and psychiatric conditions in the future.
Brain-Focused Ultrasound Therapy: Current Applications and Future Prospects
Open Access Journal of Surgery
Interventional therapies to address brain disorders carry out an additional risk due to the central nervous system’s difficult access and intrinsic complexity. Focused ultrasound therapy (FUT) is an incision-free, minimally invasive procedure that employs sound waves to produce either thermal ablation or neuromodulation according to the waveform intensity. Despite the growing evidence of the benefits and advantages of FUT, many of its potential applications have not been explored in their entirety. The mechanism of action of Focused Ultrasound involves the generation of mechanical and thermal effects on the target tissue. Magnetic resonance-guided is the most common method for delivery of FUT in the brain. Most benefits of brain FUT can be attributed to its ability to ablate target tissue or modulate neuronal activity. However, this technology can also be used to open, temporarily and reversibly, the blood-brain barrier to allow the delivery of medications directly to the affected t...
Frontiers in Psychiatry, 2022
This article describes an emerging non-invasive neuromodulatory technology, called low intensity focused ultrasound (LIFU). This technology is potentially paradigm shifting as it can deliver non-invasive and reversible deep brain neuromodulation through acoustic sonication, at millimeter precision. Low intensity focused ultrasound's spatial precision, yet non-invasive nature sets it apart from current technologies, such as transcranial magnetic or electrical stimulation and deep brain stimulation. Additionally, its reversible effects allow for the causal study of deep brain regions implicated in psychiatric illness. Studies to date have demonstrated that LIFU can safely modulate human brain activity at cortical and subcortical levels. Due to its novelty, most researchers and clinicians are not aware of the potential applications and promise of this technique, underscoring the need for foundational papers to introduce the community to LIFU. This mini-review and synthesis of recen...
Objective. While ultrasound is largely established for use in diagnostic imaging and heating therapies, its application for neuromodulation is relatively new and not well understood. The objective of the present study was to investigate issues related to interactions between focused acoustic beams and brain tissues to better understand possible limitations of transcranial ultrasound for neuromodulation. Approach. A computational model of transcranial focused ultrasound was constructed and validated against bench top experimental data. The models were then incrementally extended to address and investigate a number of issues related to the use of ultrasound for neuromodulation. These included the effect of variations in skull geometry and gyral anatomy, as well as the effect of transmission across multiple tissue and media layers, such as scalp, skull, CSF, and gray/white matter on ultrasound insertion behavior. In addition, a sensitivity analysis was run to characterize the influence...
Frontiers in Human Neuroscience
Low intensity focused ultrasound (LIFU) has been gaining traction as a non-invasive neuromodulation technology due to its superior spatial specificity relative to transcranial electrical/magnetic stimulation. Despite a growing literature of LIFU-induced behavioral modifications, the mechanisms of action supporting LIFU's parameter-dependent excitatory and suppressive effects are not fully understood. This review provides a comprehensive introduction to the underlying mechanics of both acoustic energy and neuronal membranes, defining the primary variables for a subsequent review of the field's proposed mechanisms supporting LIFU's neuromodulatory effects. An exhaustive review of the empirical literature was also conducted and studies were grouped based on the sonication parameters used and behavioral effects observed, with the goal of linking empirical findings to the proposed theoretical mechanisms and evaluating which model best fits the existing data. A neuronal intram...
Focused ultrasound modulates region-specific brain activity
NeuroImage, 2011
We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using imageguided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.
Review Paper: A Review on Brain Stimulation Using Low Intensity Focused Ultrasound
Brain stimulation techniques are important in both basic and clinical studies. Majority of well-known brain stimulating techniques have low spatial resolution or entail invasive processes. Low intensity focused ultrasound (LIFU) seems to be a proper candidate for dealing with such deficiencies. This review recapitulates studies which explored the effects of LIFU on brain structures and its function, in both research and clinical areas. Although the mechanism of LIFU action is still unclear, its different effects from molecular level up to behavioral level can be explored in animal and human brain. It can also be coupled with brain imaging assessments in future research.