scholarly journals Mechanics Of Ultrasonic Neuromodulation In A Mouse Subject

2021 ◽  
Author(s):  
Hossein Salahshoor ◽  
Hongsun Guo ◽  
Mikhail G. Shapiro ◽  
Michael Ortiz
Keyword(s):  
Pressure Wave ◽  
Focused Ultrasound ◽  
Shear Waves ◽  
Element Model ◽  
Wave Pattern ◽  
Promising Tool ◽  
Sensory Effects ◽  
The Subject ◽  
Sensory Responses ◽  
The Brain

AbstractUltrasound neuromodulation (UNM), where a region in the brain is targeted by focused ultrasound (FUS), which, in turn, causes excitation or inhibition of neural activity, has recently received considerable attention as a promising tool for neuroscience. Despite its great potential, several aspects of UNM are still unknown. An important question pertains to the off-target sensory effects of UNM and their dependence on stimulation frequency. To understand these effects, we have developed a finite-element model of a mouse, including elasticity and viscoelasticity, and used it to interrogate the response of mouse models to focused ultrasound (FUS). We find that, while some degree of focusing and magnification of the signal is achieved within the brain, the induced pressure-wave pattern is complex and delocalized. In addition, we find that the brain is largely insulated, or ‘cloaked’, from shear waves by the cranium and that the shear waves are largely carried away from the skull by the vertebral column, which acts as a waveguide. We find that, as expected, this waveguide mechanism is strongly frequency dependent, which may contribute to the frequency dependence of UNM effects. Our calculations further suggest that off-target skin locations experience displacements and stresses at levels that, while greatly attenuated from the source, could nevertheless induce sensory responses in the subject.

scholarly journals MR-Guided Focused Ultrasound: A New Generation Treatment of Parkinson's Disease, Essential Tremor and Neuropathic Pain

2014 ◽  
Vol 20 (3) ◽  
pp. 275-282 ◽  
Author(s):  
Pawel Piotr Dobrakowski ◽  
Agnieszka Kamila Machowska-Majchrzak ◽  
Beata Łabuz-Roszak ◽  
Krzysztof Grzegorz Majchrzak ◽  
Ewa Kluczewska ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Neuropathic Pain ◽  
Essential Tremor ◽  
Focused Ultrasound ◽  
Complication Rates ◽  
Mri Guidance ◽  
The Subject ◽  
New Generation ◽  
Further Development ◽  
The Brain

The application of high intense focused ultrasound (HIFU) is currently the subject of many experimental and clinical trials. The combination of HIFU with MRI guidance known as MR-guided focused ultrasound (MRgFUS) appears to be particularly promising to ablate tissues located deep in the brain. The method can be the beginning of interventional neurology and an important alternative to neurosurgery. Studies conducted to date show the effectiveness of the method both in chronic diseases and in emergency cases. The safety and effectiveness of this method have been observed in parkinsonian and essential tremor as well as in neuropathic pain. The procedure does not require anaesthesia. Ionizing radiation is not used and there is no risk of cumulative dose. Such advantages may result in low complication rates and medical justification for further development of MRgFUS.

scholarly journals Transcranial Focused Ultrasound Generates Skull-Conducted Shear Waves: Computational Model and Implications for Neuromodulation

2020 ◽  
Author(s):  
Hossein Salahshoor ◽  
Mikhail G. Shapiro ◽  
Michael Ortiz
Keyword(s):  
Focused Ultrasound ◽  
Soft Tissues ◽  
Control Strategies ◽  
Shear Waves ◽  
Element Model ◽  
Potential Method ◽  
Non Invasive ◽  
Auditory Responses ◽  
Shear Compliance ◽  
Established Technique

ABSTRACTFocused ultrasound (FUS) is an established technique for non-invasive surgery and has recently attracted considerable attention as a potential method for non-invasive neuromodulation. While the pressure waves generated by FUS in this context have been extensively studied, the accompanying shear waves are often neglected due to the relatively high shear compliance of soft tissues. However, in bony structures such as the skull, acoustic pressure can also induce significant shear waves that could propagate outside the ultrasound focus. Here, we investigate wave propagation in the human cranium by means of a finite-element model that accounts for the anatomy, elasticity and viscoelasticity of the skull and brain. We show that, when a region on the frontal lobe is subjected to FUS, the skull acts as a wave guide for shear waves, resulting in their propagation to off-target structures such as the cochlea. This effect helps explain the off-target auditory responses observed during neuromodulation experiments and informs the development of mitigation and sham control strategies.

scholarly journals Optical Imaging of Beta-Amyloid Plaques in Alzheimer’s Disease

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 255
Author(s):  
Ziyi Luo ◽  
Hao Xu ◽  
Liwei Liu ◽  
Tymish Y. Ohulchanskyy ◽  
Junle Qu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Optical Imaging ◽  
Imaging Techniques ◽  
High Sensitivity ◽  
Pathological Feature ◽  
Promising Tool ◽  
Abnormal Accumulation ◽  
Accumulation Mechanism ◽  
The Brain

Alzheimer’s disease (AD) is a multifactorial, irreversible, and incurable neurodegenerative disease. The main pathological feature of AD is the deposition of misfolded β-amyloid protein (Aβ) plaques in the brain. The abnormal accumulation of Aβ plaques leads to the loss of some neuron functions, further causing the neuron entanglement and the corresponding functional damage, which has a great impact on memory and cognitive functions. Hence, studying the accumulation mechanism of Aβ in the brain and its effect on other tissues is of great significance for the early diagnosis of AD. The current clinical studies of Aβ accumulation mainly rely on medical imaging techniques, which have some deficiencies in sensitivity and specificity. Optical imaging has recently become a research hotspot in the medical field and clinical applications, manifesting noninvasiveness, high sensitivity, absence of ionizing radiation, high contrast, and spatial resolution. Moreover, it is now emerging as a promising tool for the diagnosis and study of Aβ buildup. This review focuses on the application of the optical imaging technique for the determination of Aβ plaques in AD research. In addition, recent advances and key operational applications are discussed.

scholarly journals Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Weber-Adrian ◽  
Rikke Hahn Kofoed ◽  
Joseph Silburt ◽  
Zeinab Noroozian ◽  
Kairavi Shah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Intravenous Injection ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Fluorescent Protein ◽  
Gfp Expression ◽  
Peripheral Organs ◽  
Neuronal Expression ◽  
Green Fluorescent ◽  
The Brain

AbstractNon-surgical gene delivery to the brain can be achieved following intravenous injection of viral vectors coupled with transcranial MRI-guided focused ultrasound (MRIgFUS) to temporarily and locally permeabilize the blood–brain barrier. Vector and promoter selection can provide neuronal expression in the brain, while limiting biodistribution and expression in peripheral organs. To date, the biodistribution of adeno-associated viruses (AAVs) within peripheral organs had not been quantified following intravenous injection and MRIgFUS delivery to the brain. We evaluated the quantity of viral DNA from the serotypes AAV9, AAV6, and a mosaic AAV1&2, expressing green fluorescent protein (GFP) under the neuron-specific synapsin promoter (syn). AAVs were administered intravenously during MRIgFUS targeting to the striatum and hippocampus in mice. The syn promoter led to undetectable levels of GFP expression in peripheral organs. In the liver, the biodistribution of AAV9 and AAV1&2 was 12.9- and 4.4-fold higher, respectively, compared to AAV6. The percentage of GFP-positive neurons in the FUS-targeted areas of the brain was comparable for AAV6-syn-GFP and AAV1&2-syn-GFP. In summary, MRIgFUS-mediated gene delivery with AAV6-syn-GFP had lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.

scholarly journals Focused Ultrasound Strategies for Brain Tumor Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Adomas Bunevicius ◽  
Nathan Judson McDannold ◽  
Alexandra J Golby
Keyword(s):  
Brain Tumors ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Tumor Therapy ◽  
Drug Distribution ◽  
Low Frequency ◽  
Tissue Level ◽  
Chemotherapeutic Agents ◽  
Promising Tool ◽  
Investigational Agents

Abstract BACKGROUND A key challenge in the medical treatment of brain tumors is the limited penetration of most chemotherapeutic agents across the blood–brain barrier (BBB) into the tumor and the infiltrative margin around the tumor. Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising tool to enhance the delivery of chemotherapeutic agents into brain tumors. OBJECTIVE To review the mechanism of FUS, preclinical evidence, and clinical studies that used low-frequency FUS for a BBB opening in gliomas. METHODS Literature review. RESULTS The potential of externally delivered low-intensity ultrasound for a temporally and spatially precise and predictable disruption of the BBB has been investigated for over a decade, yielding extensive preclinical literature demonstrating that FUS can disrupt the BBB in a spatially targeted and temporally reversible manner. Studies in animal models documented that FUS enhanced the delivery of numerous chemotherapeutic and investigational agents across the BBB and into brain tumors, including temozolomide, bevacizumab, 1,3-bis (2-chloroethyl)-1-nitrosourea, doxorubicin, viral vectors, and cells. Chemotherapeutic interventions combined with FUS slowed tumor progression and improved animal survival. Recent advances of MRgFUS systems allow precise, temporally and spatially controllable, and safe transcranial delivery of ultrasound energy. Initial clinical evidence in glioma patients has shown the efficacy of MRgFUS in disrupting the BBB, as demonstrated by an enhanced gadolinium penetration. CONCLUSION Thus far, a temporary disruption of the BBB followed by the administration of chemotherapy has been both feasible and safe. Further studies are needed to determine the actual drug delivery, including the drug distribution at a tissue-level scale, as well as effects on tumor growth and patient prognosis.

scholarly journals VI. On the comparative structure of the brain in rodents

1882 ◽  
Vol 33 (216-219) ◽  
pp. 15-21
Keyword(s):  
Olfactory Organ ◽  
Cortical Surface ◽  
Complex Relationship ◽  
Comparative Structure ◽  
The Subject ◽  
The Brain

I have endeavoured in this abstract to summarise the results of my recent researches into the minute structure of the brain in the smaller Rodents. The pig and sheep, which were the subjects of my former memoir, possess a highly developed olfactory apparatus conjoined to a well convoluted cortical surface; but in the smaller animals now under consideration the surface of the hemispheres is almost perfectly smooth, while the olfactory organ, from its comparative size and complex relationship, has an important part to play in the architecture of the brain. Animals possessing the latter type of cerebrum have been classed together as the Osmatic Lissencéphales, in contradistinction to those which were the subject of my former enquiries, the Osmatic Gyren-céphales. My researches into the structure of the brain of prominent members of the former group, viz., the rabbit and rat, may be considered under two heads:— ( a .) The histology of the complete cortical envelope.

Transfer of consciousness. Considering its possibility or fantasy from the religious and scientific perspectives

DIALOGO ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. 189-200
Author(s):  
Tudor-Cosmin Ciocan ◽  
Any Docu Axelerad ◽  
Maria CIOCAN ◽  
Alina Zorina Stroe ◽  
Silviu Docu Axelerad ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Eternal Life ◽  
Human Consciousness ◽  
Religious Believer ◽  
Actual Knowledge ◽  
Holistic Understanding ◽  
The World ◽  
The Subject ◽  
Human Feature ◽  
The Brain

Ancient beliefs such as astral projection, human possession, abduction and other similar are not only universal, taught by all religions, but also used as premises for core believes/expectations, such as after-life, eternal damnation, reincarnation, and many others. Transferring Consciousness to a Synthetic Body is also a feature of interest in our actual knowledge, both religious as for science. If immortality were an option, would you take it into consideration more seriously? Most people would probably dismiss the question since immortality isn’t a real deal to contract. But what if having eternal life was a possibility in today’s world? The possibility of the transfer of human consciousness to a synthetic body can soon become a reality, and it could help the world for the better. Thus, until recently, the subject was mostly proposed by religion(s) and saw as a spiritual [thus, not ‘materially real’ or ‘forthwith accomplishable’] proposal therefore not really fully engaged or trust if not a religious believer. Now, technology is evolving, and so are we. The world has come to a point where artificial intelligence is breaking the boundaries of our perception of human consciousness and intelligence. And with this so is our understanding about the ancient question ‘who are we?’ concerning consciousness and how this human feature sticks to our body or it can become an entity beyond the material flesh. Without being exhaustive with the theme's development [leaving enough room for further investigations], we would like to take it for a spin and see how and where the religious and neuroscience realms intersect with it for a global, perhaps holistic understanding. Developments in neurotechnology favor the brain to broaden its physical control further the restraints of the human body. Accordingly, it is achievable to both acquire and provide information from and to the brain and also to organize feedback processes in which a person's thoughts can influence the activity of a computer or reversely.

scholarly journals Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity

2018 ◽  
Vol 25 (5) ◽  
pp. 455-474 ◽  
Author(s):  
Colm Cunningham ◽  
Aisling Dunne ◽  
Ana Belen Lopez-Rodriguez
Keyword(s):  
Neural Circuit ◽  
Phenotypic Diversity ◽  
Significant Heterogeneity ◽  
Therapeutic Implications ◽  
Numerous Cell ◽  
Health And Disease ◽  
The Subject ◽  
The Brain ◽  
Substantial Heterogeneity ◽  
Homogenous Population

Astrocytes are the most numerous cell type in the brain and perform several essential functions in supporting neuronal metabolism and actively participating in neural circuit and behavioral function. They also have essential roles as innate immune cells in responding to local neuropathology, and the manner in which they respond to brain injury and degeneration is the subject of increasing attention in neuroscience. Although activated astrocytes have long been thought of as a relatively homogenous population, which alter their phenotype in a relatively stereotyped way upon central nervous system injury, the last decade has revealed substantial heterogeneity in the basal state and significant heterogeneity of phenotype during reactive astrocytosis. Thus, phenotypic diversity occurs at two distinct levels: that determined by regionality and development and that determined by temporally dynamic changes to the environment of astrocytes during pathology. These inflammatory and pathological states shape the phenotype of these cells, with different consequences for destruction or recovery of the local tissue, and thus elucidating these phenotypic changes has significant therapeutic implications. In this review, we will focus on the phenotypic heterogeneity of astrocytes in health and disease and their propensity to change that phenotype upon subsequent stimuli.

scholarly journals Short-term saccadic adaptation in the macaque monkey: a binocular mechanism

2013 ◽  
Vol 109 (2) ◽  
pp. 518-545 ◽  
Author(s):  
K. P. Schultz ◽  
C. Busettini
Keyword(s):  
Saccadic Eye Movements ◽  
Initial Response ◽  
Macaque Monkey ◽  
Double Step ◽  
Adaptive Process ◽  
Adaptive Mechanisms ◽  
Second Shift ◽  
The Subject ◽  
The Brain ◽  
Saccadic Responses

Saccadic eye movements are rapid transfers of gaze between objects of interest. Their duration is too short for the visual system to be able to follow their progress in time. Adaptive mechanisms constantly recalibrate the saccadic responses by detecting how close the landings are to the selected targets. The double-step saccadic paradigm is a common method to simulate alterations in saccadic gain. While the subject is responding to a first target shift, a second shift is introduced in the middle of this movement, which masks it from visual detection. The error in landing introduced by the second shift is interpreted by the brain as an error in the programming of the initial response, with gradual gain changes aimed at compensating the apparent sensorimotor mismatch. A second shift applied dichoptically to only one eye introduces disconjugate landing errors between the two eyes. A monocular adaptive system would independently modify only the gain of the eye exposed to the second shift in order to reestablish binocular alignment. Our results support a binocular mechanism. A version-based saccadic adaptive process detects postsaccadic version errors and generates compensatory conjugate gain alterations. A vergence-based saccadic adaptive process detects postsaccadic disparity errors and generates corrective nonvisual disparity signals that are sent to the vergence system to regain binocularity. This results in striking dynamical similarities between visually driven combined saccade-vergence gaze transfers, where the disparity is given by the visual targets, and the double-step adaptive disconjugate responses, where an adaptive disparity signal is generated internally by the saccadic system.

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