Ultrasound Technologies for Imaging and Modulating Neural Activity

Rabut, Claire; Yoo, Seung Jick; Hurt, Robert C.; Jin, Zhiyang; Li, Hongsyi; Guo, Hongsun; Ling, Bill; Shapiro, Mikhail G.

doi:10.1016/j.neuron.2020.09.003

Cited by 168 publications

(134 citation statements)

References 176 publications

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“…Functional ultrasound interrogation and manipulation of brain networks have been proposed to overcome some of fMRI's shortcomings in specificity, spatiotemporal resolution, and portability (Rabut et al, 2020). Cortical and deep thalamic sensory responses to stimulation were characterized by dopplerultrasound imaging (Macé et al, 2011).…”

Section: Imaging Of Brain Hemodynamicsmentioning

confidence: 99%

Photoacoustic Neuroimaging - Perspectives on a Maturing Imaging Technique and its Applications in Neuroscience

Bodea

Westmeyer

2021

Front. Neurosci.

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A prominent goal of neuroscience is to improve our understanding of how brain structure and activity interact to produce perception, emotion, behavior, and cognition. The brain’s network activity is inherently organized in distinct spatiotemporal patterns that span scales from nanometer-sized synapses to meter-long nerve fibers and millisecond intervals between electrical signals to decades of memory storage. There is currently no single imaging method that alone can provide all the relevant information, but intelligent combinations of complementary techniques can be effective. Here, we thus present the latest advances in biomedical and biological engineering on photoacoustic neuroimaging in the context of complementary imaging techniques. A particular focus is placed on recent advances in whole-brain photoacoustic imaging in rodent models and its influential role in bridging the gap between fluorescence microscopy and more non-invasive techniques such as magnetic resonance imaging (MRI). We consider current strategies to address persistent challenges, particularly in developing molecular contrast agents, and conclude with an overview of potential future directions for photoacoustic neuroimaging to provide deeper insights into healthy and pathological brain processes.

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Section: Imaging Of Brain Hemodynamicsmentioning

confidence: 99%

Photoacoustic Neuroimaging - Perspectives on a Maturing Imaging Technique and its Applications in Neuroscience

Bodea

Westmeyer

2021

Front. Neurosci.

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“…Several mechanosensitive ion channels and proteins have been proposed as sonogenetic actuators, for example TREK-1/2 [13], MscL [14], Piezo1 [15], TRPA1 [16], Mscl-G22S [17], and prestin [18]. However, most reported studies were performed in vitro with only preliminary in vivo studies suggesting that some of these channels can be activated by ultrasound in the mouse brain [19]. Recent technological advances have enabled noninvasive and spatially targeted FUS heating in the human brain with precise control of temperature based on real-time temperature monitoring using magnetic resonance (MR) thermometry [20].…”

Section: Introductionmentioning

confidence: 99%

Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation

Yang

Pacia

et al. 2021

Brain Stimulation

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Background: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain.Objective: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and celltype-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect. Methods: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon calcium imaging. Behavioral response evoked by sonothermogenetic stimulation at a deep brain target was recorded in freely moving mice. Immunohistochemistry staining of ex vivo brain slices was performed to evaluate the safety of FUS sonication. Results: TRPV1 was found to be an ultrasound-sensitive ion channel. FUS sonication at the mouse brain in vivo selectively activated neurons that were genetically modified to express TRPV1. Temporally precise activation of TRPV1-expressing neurons was achieved with its success rate linearly correlated with the peak temperature within the FUS-targeted brain region as measured by in vivo magnetic resonance thermometry. FUS stimulation of TRPV1-expressing neurons at the striatum repeatedly evoked locomotor behavior in freely moving mice. FUS sonication was confirmed to be safe based on inspection of neuronal integrity, inflammation, and apoptosis markers. Conclusions: This noninvasive and cell-type-specific neuromodulation approach with the capability to stimulate deep brain has the promise to advance the study of the intact nervous system and uncover new ways to treat neurological disorders.

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“…In addition to the mechanical effects, another possible mechanism of the neuromodulatory effects of LI-TUS is its thermal effects in tissues. A temperature rises caused by LI-TUS lead to evoke heat transfers which alter in the membrane properties as a result in depolarization (Tyler et al, 2018;Kamimura et al, 2020;Rabut et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review

et al. 2021

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Background: Although low-intensity transcranial ultrasound stimulation (LI-TUS) has received more recognition for its neuromodulation potential, there remains a crucial knowledge gap regarding the neuromodulatory effects of LI-TUS and its potential for translation as a therapeutic tool in humans.Objective: In this review, we summarized the findings reported by recently published studies regarding the effect of LI-TUS on neuromodulation in both animals and humans. We also aim to identify challenges and opportunities for the translation process.Methods: A literature search of PubMed, Medline, EMBASE, and Web of Science was performed from January 2019 to June 2020 with the following keywords and Boolean operators: [transcranial ultrasound OR transcranial focused ultrasound OR ultrasound stimulation] AND [neuromodulation]. The methodological quality of the animal studies was assessed by the SYRCLE's risk of bias tool, and the quality of human studies was evaluated by the PEDro score and the NIH quality assessment tool.Results: After applying the inclusion and exclusion criteria, a total of 26 manuscripts (24 animal studies and two human studies) out of 508 reports were included in this systematic review. Although both inhibitory (10 studies) and excitatory (16 studies) effects of LI-TUS were observed in animal studies, only inhibitory effects have been reported in primates (five studies) and human subjects (two studies). The ultrasonic parameters used in animal and human studies are different. The SYRCLE quality score ranged from 25 to 43%, with a majority of the low scores related to performance and detection bias. The two human studies received high PEDro scores (9/10).Conclusion: LI-TUS appears to be capable of targeting both superficial and deep cerebral structures to modulate cognitive or motor behavior in both animals and humans. Further human studies are needed to more precisely define the effective modulation parameters and thereby translate this brain modulatory tool into the clinic.

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Ultrasound Technologies for Imaging and Modulating Neural Activity

Cited by 168 publications

References 176 publications

Photoacoustic Neuroimaging - Perspectives on a Maturing Imaging Technique and its Applications in Neuroscience

Photoacoustic Neuroimaging - Perspectives on a Maturing Imaging Technique and its Applications in Neuroscience

Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation

Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review

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