scholarly journals Real time and delayed effects of subcortical low intensity focused ultrasound

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua A. Cain ◽  
Shakthi Visagan ◽  
Micah A. Johnson ◽  
Julia Crone ◽  
Robin Blades ◽  
...  
Keyword(s):  
Large Scale ◽  
Focused Ultrasound ◽  
Blood Oxygenation ◽  
Brain Nuclei ◽  
Delayed Effects ◽  
Non Invasive ◽  
Low Intensity ◽  
Oxygenation Level ◽  
Basal Ganglia Structures ◽  
Deep Brain

AbstractDeep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

scholarly journals Real Time and Delayed Effects of Subcortical Low Intensity Focused Ultrasound

2020 ◽  
Author(s):  
Joshua A. Cain ◽  
Shakthi Visagan ◽  
Micah A. Johnson ◽  
Julia Crone ◽  
Robin Blades ◽  
...  
Keyword(s):  
Large Scale ◽  
Focused Ultrasound ◽  
Blood Oxygenation ◽  
Brain Nuclei ◽  
Delayed Effects ◽  
Non Invasive ◽  
Low Intensity ◽  
Oxygenation Level ◽  
Basal Ganglia Structures ◽  
Deep Brain

ABSTRACTDeep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

Implication of Auditory Confounding in Interpreting Somatosensory and Motor Responses in Low-Intensity Transcranial Focused Ultrasound Stimulation

2021 ◽  
Author(s):  
Christine Park ◽  
Mengyue Chen ◽  
Taewon Kim
Keyword(s):  
Focused Ultrasound ◽  
Auditory Pathway ◽  
Localization Accuracy ◽  
Motor Responses ◽  
Non Invasive ◽  
Low Intensity ◽  
Ultrasound Stimulation ◽  
Transcranial Focused Ultrasound ◽  
Indirect Stimulation ◽  
Stimulation Of

Low-intensity transcranial focused ultrasound (LI-tFUS) stimulation is a non-invasive neuromodulation tool that demonstrates high target localization accuracy and depth penetration. It has been shown to modulate activities in the primary motor and somatosensory cortex. Previous studies in animals and humans acknowledged the possibility of indirect stimulation of the peripheral auditory pathway that could confound the somatosensory and motor responses observed with LI-tFUS stimulation. Here, we discuss the implications and interpretations of auditory confounding in the context of neuromodulation.

scholarly journals Vagal nerve stimulation triggers widespread responses and alters large-scale functional connectivity in the rat brain

2017 ◽  
Author(s):  
Jiayue Cao ◽  
Kun-Han Lu ◽  
Terry L. Powley ◽  
Zhongming Liu
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Large Scale ◽  
Time Course ◽  
Brain Networks ◽  
Blood Oxygenation ◽  
7 Tesla ◽  
Sprague Dawley ◽  
Wide Range ◽  
Oxygenation Level

AbstractVagus nerve stimulation (VNS) is a therapy for epilepsy and depression. However, its efficacy varies and its mechanism remains unclear. Prior studies have used functional magnetic resonance imaging (fMRI) to map brain activations with VNS in human brains, but have reported inconsistent findings. The source of inconsistency is likely attributable to the complex temporal characteristics of VNS-evoked fMRI responses that cannot be fully explained by simplified response models in the conventional model-based analysis for activation mapping. To address this issue, we acquired 7-Tesla blood oxygenation level dependent fMRI data from anesthetized Sprague–Dawley rats receiving electrical stimulation at the left cervical vagus nerve. Using spatially independent component analysis, we identified 20 functional brain networks and detected the network-wise activations with VNS in a data-driven manner. Our results showed that VNS activated 15 out of 20 brain networks, and the activated regions covered >76% of the brain volume. The time course of the evoked response was complex and distinct across regions and networks. In addition, VNS altered the strengths and patterns of correlations among brain networks relative to those in the resting state. The most notable changes in network-network interactions were related to the limbic system. Together, such profound and widespread effects of VNS may underlie its unique potential for a wide range of therapeutics to relieve central or peripheral conditions.

scholarly journals Low Intensity Focused Ultrasound Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer

2021 ◽  
Author(s):  
Qian Zhang ◽  
Wen Wang ◽  
Hongyuan Shen ◽  
Hongyu Tao ◽  
Yating Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ultrasound Imaging ◽  
Focused Ultrasound ◽  
Metastatic Breast ◽  
Sonodynamic Therapy ◽  
Non Invasive ◽  
Low Intensity ◽  
Negative Effect

Abstract The metastasis of breast cancer is believed to have a negative effect on its prognosis. Benefiting from the remarkable deep-penetrating and non-invasive characteristics, sonodynamic therapy (SDT) demonstrates a whole series of potential leading to cancer treatment. To relieve the limitation of monotherapy, a multifunctional nanoplatform has been explored to realize the synergistic treatment efficiency. Herein, we establish a novel multifunctional nano-system which encapsulates chlorin e6 (Ce6, for SDT), perfluoropentane (PFP, for ultrasound imaging), and docetaxel (DTX, for chemotherapy) in a well-designed PLGA core-shell structure. The synergistic nanoparticle (CPDP NPs) featured with excellent biocompatibility and stability primarily enables its further application. Upon low intensity focused ultrasound (LIFU) irradiation, the enhanced ultrasound imaging could be revealed both in vitro and in vivo. More importantly, combined with LIFU, the nanoparticle exhibits intriguing antitumor capability through Ce6 induced cytotoxic reactive oxygen species as well as DTX releasing to generate a concerted therapeutic efficiency. Furthermore, this treating strategy actives a strong anti-metastasis capability by which lung metastatic nodules have been significantly reduced. The results indicate that the SDT-oriented nanoplatform combined with chemotherapy could be provided as a promising approach in elevating effective synergistic therapy and suppressing lung metastasis of breast cancer.

scholarly journals Advanced MRI techniques for transcranial high intensity focused ultrasound targeting

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2664-2672
Author(s):  
Bhavya R Shah ◽  
Vance T Lehman ◽  
Timothy J Kaufmann ◽  
Daniel Blezek ◽  
Jeff Waugh ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Magnetic Resonance ◽  
High Intensity ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Brain Nuclei ◽  
Intermediate Nucleus ◽  
Mri Sequences ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

Abstract Magnetic resonance guided high intensity focused ultrasound is a novel, non-invasive, image-guided procedure that is able to ablate intracranial tissue with submillimetre precision. It is currently FDA approved for essential tremor and tremor dominant Parkinson’s disease. The aim of this update is to review the limitations of current landmark-based targeting techniques of the ventral intermediate nucleus and demonstrate the role of emerging imaging techniques that are relevant for both magnetic resonance guided high intensity focused ultrasound and deep brain stimulation. A significant limitation of standard MRI sequences is that the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei cannot be clearly identified. This paper provides original, annotated images demarcating the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei on advanced MRI sequences such as fast grey matter acquisition T1 inversion recovery, quantitative susceptibility mapping, susceptibility weighted imaging, and diffusion tensor imaging tractography. Additionally, the paper reviews clinical efficacy of targeting with these novel MRI techniques when compared to current established landmark-based targeting techniques. The paper has widespread applicability to both deep brain stimulation and magnetic resonance guided high intensity focused ultrasound.

scholarly journals Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification

2020 ◽  
Author(s):  
Sangjin Yoo ◽  
David R. Mittelstein ◽  
Robert Hurt ◽  
Jerome Lacroix ◽  
Mikhail G. Shapiro
Keyword(s):  
Ion Channels ◽  
Large Scale ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Cellular Mechanisms ◽  
Temperature Changes ◽  
Non Invasive ◽  
Neuroscience Research ◽  
Ultrasonic Stimulation ◽  
Further Development

ABSTRACTUltrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research.

scholarly journals The Role of Cerebrovascular-Reactivity Mapping in Functional MRI: Calibrated fMRI and Resting-State fMRI

2021 ◽  
Vol 12 ◽  
Author(s):  
J. Jean Chen ◽  
Claudine J. Gauthier
Keyword(s):  
Functional Mri ◽  
Resting State ◽  
Resting State Fmri ◽  
Blood Oxygenation ◽  
Cerebrovascular Reactivity ◽  
Resting State Functional Connectivity ◽  
Non Invasive ◽  
Oxygenation Level ◽  
Calibrated Fmri

Task and resting-state functional MRI (fMRI) is primarily based on the same blood-oxygenation level-dependent (BOLD) phenomenon that MRI-based cerebrovascular reactivity (CVR) mapping has most commonly relied upon. This technique is finding an ever-increasing role in neuroscience and clinical research as well as treatment planning. The estimation of CVR has unique applications in and associations with fMRI. In particular, CVR estimation is part of a family of techniques called calibrated BOLD fMRI, the purpose of which is to allow the mapping of cerebral oxidative metabolism (CMRO2) using a combination of BOLD and cerebral-blood flow (CBF) measurements. Moreover, CVR has recently been shown to be a major source of vascular bias in computing resting-state functional connectivity, in much the same way that it is used to neutralize the vascular contribution in calibrated fMRI. Furthermore, due to the obvious challenges in estimating CVR using gas challenges, a rapidly growing field of study is the estimation of CVR without any form of challenge, including the use of resting-state fMRI for that purpose. This review addresses all of these aspects in which CVR interacts with fMRI and the role of CVR in calibrated fMRI, provides an overview of the physiological biases and assumptions underlying hypercapnia-based CVR and calibrated fMRI, and provides a view into the future of non-invasive CVR measurement.

scholarly journals Sonication of the Anterior Thalamus with MRI-Guided Low Intensity Focused Ultrasound Pulsation (LIFUP) Changes Pain Thresholds in Healthy Adults: A Double-Blind, Concurrent LIFUP/MRI Study

2020 ◽  
Author(s):  
Bashar W. Badran ◽  
Kevin Caulfield ◽  
Sasha Stomberg-Firestein ◽  
Philip Summers ◽  
Logan T. Dowdle ◽  
...  
Keyword(s):  
Focused Ultrasound ◽  
Ultrasonic Waves ◽  
Thermal Stimulus ◽  
Healthy Individuals ◽  
Double Blind ◽  
Pain Thresholds ◽  
Thermal Pain ◽  
Low Intensity ◽  
Anterior Thalamus ◽  
Deep Brain

AbstractBackgroundLow Intensity Focused Ultrasound Pulsation (LIFUP) is a noninvasive brain stimulation method that may modulate deep brain structures using ultrasonic waves. Presently there are limited studies in humans rigorously assessing behavioral effects following LIFUP sonication of deep brain nuclei. As an initial test, we investigated whether sonication of the anterior thalamus, a central relay structure of nociception, would modulate thermal pain thresholds in healthy individuals.MethodsWe enrolled 19 healthy individuals in this three-visit, double-blind, randomized, sham-controlled, crossover trial. Participants attended a first MRI screening visit to acquire anatomical scans for LIFUP targeting. They then attended two identical experimental LIFUP/MRI visits (counterbalanced by condition) at least one-week apart. Within the MRI scanner, participants received two, 10-minute sessions of either active or sham LIFUP spread 10 minutes apart to the right anterior thalamus [Fundamental frequency:650khz, pulse repetition frequency: 10 HZ, Pulse Width: 5ms, Duty Cycle: 5%, Sonication Duration: 30s, Inter-Sonication Interval: 30 s, Number of Sonications: 10, ISPTA.3 719 mW/cm2]. Each 10-minute session was delivered in a block design (30s ON, 30s OFF). The primary outcome measure was quantitative sensory thresholding (QST), measuring sensory, pain, and tolerance thresholds to a thermal stimulus applied to the left forearm before and after LIFUP. Thermal stimuli were also applied in the scanner during certain blocks, either alone, or during LIFUP.ResultsTwo 10-minute sessions of thalamic LIFUP produced a significant antinociceptive effect on pain thresholds. Temperature sensitivity increases were significantly attenuated (timeXcondition p=0.046) after active LIFUP (0.51 degree change) relative to sham stimulation (1.08 degrees). LIFUP also changed sensory and tolerance thresholds mathematically but this was not statistically significant with this sample. LIFUP delivered concurrently with thermal pain had no immediate behavioral effect.ConclusionsTwo, 10-minute sessions of anterior thalamic LIFUP has antinociceptive effects in healthy individuals. Future studies should optimize the parameter space and dose and perhaps investigate multi-session LIFUP interventions for pain disorders.

Non-Invasive, Focal Disconnection of Brain Circuitry Using Magnetic Resonance-Guided Low-Intensity Focused Ultrasound to Deliver a Neurotoxin

2016 ◽  
Vol 42 (9) ◽  
pp. 2261-2269 ◽  
Author(s):  
Yanrong Zhang ◽  
Hongying Tan ◽  
Edward H. Bertram ◽  
Jean-François Aubry ◽  
Maria-Beatriz Lopes ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Focused Ultrasound ◽  
Non Invasive ◽  
Low Intensity ◽  
Brain Circuitry

scholarly journals Discovering frequency sensitive thalamic nuclei from EEG microstate informed resting state fMRI

2020 ◽  
Author(s):  
Simon Schwab
Keyword(s):  
Resting State ◽  
Large Scale ◽  
Resting State Fmri ◽  
Blood Oxygenation ◽  
Strongly Correlated ◽  
Thalamic Nuclei ◽  
Frequency Bands ◽  
Beta Frequency Band ◽  
Oxygenation Level ◽  
Beta Frequency

Microstates (MS), the fingerprints of the momentarily and time-varying states of the brain derived from electroencephalography (EEG), are associated with the resting state networks (RSNs). However, using MS fluctuations along different EEG frequency bands to model the functional MRI (fMRI) signal has not been investigated so far, or elucidated the role of the thalamus as a fundamental gateway and a putative key structure in cortical functional networks. Therefore, in the current study, we used MS predictors in standard frequency bands to predict blood oxygenation level dependent (BOLD) signal fluctuations. We discovered that multivariate modeling of BOLD-fMRI using six EEG-MS classes in eight frequency bands strongly correlated with thalamic areas and large-scale cortical networks. Thalamic nuclei exhibited distinct patterns of correlations for individual MS that were associated with specific EEG frequency bands. Anterior and ventral thalamic nuclei were sensitive to the beta frequency band, medial nuclei were sensitive to both alpha and beta frequency bands, and posterior nuclei such as the pulvinar were sensitive to delta and theta frequency bands. These results demonstrate that EEG-MS informed fMRI can elucidate thalamic activity not directly observable by EEG, which may be highly relevant to understand the rapid formation of thalamocortical networks.

Sign in / Sign up

Export Citation Format

Share Document