New Probes and Targets for Hypoxia Imaging

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Description
Magnetic resonance imaging (MRI) is a noninvasive imaging modality, which is used for many different applications. The versatility of MRI is in acquiring high resolution anatomical and functional images with no use of ionizing radiation. The contrast in MR images

Magnetic resonance imaging (MRI) is a noninvasive imaging modality, which is used for many different applications. The versatility of MRI is in acquiring high resolution anatomical and functional images with no use of ionizing radiation. The contrast in MR images can be engineered by two different mechanisms with imaging parameters (TR, TE, α) and/or contrast agents. The contrast in the former is influenced by the intrinsic properties of the tissue (T1, T2, ρ), while the contrast agents change the relaxation rate of the protons to enhance contrast. Contrast agents have attracted a lot of attention because they can be modified with targeting groups to shed light on some physiological and biological questions, such as the presence of hypoxia in a tissue. Hypoxia, defined as lack of oxygen, has many known ramifications on the outcome of therapy in any condition. Hence its study is very important. The standard gold method to detect hypoxia, immunohistochemical (IHC) staining of pimonidazole, is invasive; however, there are many research groups focused on developing new and mainly noninvasive methods to investigate hypoxia in different tissues.Previously, a novel nitroimidazole-based T1 contrast agent, gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI ), has been synthesized and characterized on subcutaneous prostate and lung tumor models. Here, its efficacy and performance on traumatic brain injuries and brain tumors are studied. The pharmacokinetic properties of the contrast agent the perfusion properties of brain tumors are investigated. These results can be used in personalized therapies for more effective results for patients. Gadolinium (Gd), which is a strongly paramagnetic heavy metal, is routinely and widely used as an MR contrast agent by chelation with a biocompatible ligand which is typically cleared through the kidneys. While widely used, there are serious concerns for patients with impaired kidney function, as well as recent studies showed Gd accumulation in the bone and brain. Iron as a physiological ion is also capable of generating contrast in MR images. Here synthesis and characterization of an iron-based hypoxia targeting contrast agent is proposed to eliminate Gd-related complications and provide a cheaper and more economical alternative contrast agent to detect hypoxia.
Date Created
2021
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Neural Activity Mapping Using Electromagnetic Fields: An In Vivo Preliminary Functional Magnetic Resonance Electrical Impedance Tomography (fMREIT) Study

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Description
Electromagnetic fields (EMFs) generated by biologically active neural tissue are critical in the diagnosis and treatment of neurological diseases. Biological EMFs are characterized by electromagnetic properties such as electrical conductivity, permittivity and magnetic susceptibility. The electrical conductivity of active

Electromagnetic fields (EMFs) generated by biologically active neural tissue are critical in the diagnosis and treatment of neurological diseases. Biological EMFs are characterized by electromagnetic properties such as electrical conductivity, permittivity and magnetic susceptibility. The electrical conductivity of active tissue has been shown to serve as a biomarker for the direct detection of neural activity, and the diagnosis, staging and prognosis of disease states such as cancer. Magnetic resonance electrical impedance tomography (MREIT) was developed to map the cross-sectional conductivity distribution of electrically conductive objects using externally applied electrical currents. Simulation and in vitro studies of invertebrate neural tissue complexes demonstrated the correlation of membrane conductivity variations with neural activation levels using the MREIT technique, therefore laying the foundation for functional MREIT (fMREIT) to detect neural activity, and future in vivo fMREIT studies.



The development of fMREIT for the direct detection of neural activity using conductivity contrast in in vivo settings has been the focus of the research work presented here. An in vivo animal model was developed to detect neural activity initiated changes in neuronal membrane conductivities under external electrical current stimulation. Neural activity was induced in somatosensory areas I (SAI) and II (SAII) by applying electrical currents between the second and fourth digits of the rodent forepaw. The in vivo animal model involved the use of forepaw stimulation to evoke somatosensory neural activations along with hippocampal fMREIT imaging currents contemporaneously applied under magnetic field strengths of 7 Tesla. Three distinct types of fMREIT current waveforms were applied as imaging currents under two inhalants – air and carbogen. Active regions in the somatosensory cortex showed significant apparent conductivity changes as variations in fMREIT phase (φ_d and ∇^2 φ_d) signals represented by fMREIT activation maps (F-tests, p <0.05). Consistent changes in the standard deviation of φ_d and ∇^2 φ_d in cortical voxels contralateral to forepaw stimulation were observed across imaging sessions. These preliminary findings show that fMREIT may have the potential to detect conductivity changes correlated with neural activity.
Date Created
2020
Agent

Electromagnetic Field Strength Analysis with Deep Brain Stimulation in Parkinson's Patients

Description
Deep Brain Stimulation (DBS) is a stimulating therapy currently used to treat the motor disabilities that occur as a result of Parkinson’s disease (PD). Previous literature has proven the DBS to be an effective treatment in the effects of PD

Deep Brain Stimulation (DBS) is a stimulating therapy currently used to treat the motor disabilities that occur as a result of Parkinson’s disease (PD). Previous literature has proven the DBS to be an effective treatment in the effects of PD but the mechanism to validating this phenomenon is poorly understood. In this study, an evaluation of the DBS mechanism was analyzed in patients who received both contralateral and ipsilateral stimulation by the DBS electrode in relation to the recording microelectrode. I hypothesize that the data recorded from the neural tissue of the Parkinson’s patients will exhibit increased electromagnetic field (EMF) fall-off as spatial distance increases among the DBS lead and the microelectrode within the subthalamic nucleus (STN) as a result of the interaction between the EMF exuded by DBS and the neural tissue. Results depicted that EMF fall-off values increased with distance, observable upon comparing ipsilateral and contralateral patient data. The resulting analysis supported this phenomenon evidenced by the production of greater peak voltage amplitudes in ipsilateral patient stimulation with respect to time when compared to contralateral patient stimulation. The understanding of EMF strength and the associated trends among this data are vital to the progression and continued development of the DBS field relative to future research.
Date Created
2020-12
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Biomechanical Micromotion at the Neural Interface Modulates Intercellular Membrane Potential In-Vivo

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Description
Brain micromotion is a phenomenon that arises from basic physiological functions such as respiration (breathing) and vascular pulsation (pumping blood or heart rate). These physiological processes cause small micro displacements of 2-4µm for vascular pulsation and 10-30µm for respiration, in

Brain micromotion is a phenomenon that arises from basic physiological functions such as respiration (breathing) and vascular pulsation (pumping blood or heart rate). These physiological processes cause small micro displacements of 2-4µm for vascular pulsation and 10-30µm for respiration, in rat models. One problem related to micromotion is the instability of the probe and its ability to acquire stable neural recordings in chronic studies. It has long been thought the membrane potential (MP) changes due to micromotion in the presence of brain implants were an artefact caused by the implant. Here is shown that intracellular membrane potential changes are a consequence of the activation of mechanosensitive ion channels at the neural interface. A combination of aplysia and rat animal models were used to show activation of mechanosensitive ion channels is occurring during a neural recording. During simulated micromotion of displacements of 50μm and 100μm at a frequency of 1 Hz, showed a change of 8 and 10mV respectively and that the addition of Ethylenediaminetetraacetic acid (EDTA) inhibited the membrane potential changes. The application of EDTA showed a 71% decrease in changes in membrane potential changes due to micromotion. Simulation of breathing using periodic motion of a probe in an Aplysia model showed that there were no membrane potential changes for <1.5kPa and action potentials were observed at >3.1kPa. Drug studies utilizing 5-HT showed an 80% reduction in membrane potentials. To validate the electrophysiological changes due to micromotion in a rat model, a double barrel pipette for simultaneous recording and drug delivery was designed, the drug delivery tip was recessed from the recording tip no greater than 50μm on average. The double barrel pipette using iontophoresis was used to deliver 30 μM of Gadolinium Chloride (Gd3+) into the microenvironment of the cell. Here is shown a significant reduction in membrane potential for n = 13 cells across 4 different rats tested using Gd3+. Membrane potential changes related to breathing and vascular pulsation were reduced between approximately 0.25-2.5 mV for both breathing and heart rate after the addition of Gd3+, a known mechanosensitive ion channel blocker.
Date Created
2020
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The Safety, Tolerability, and Efficacy of Electrical Nerve Stimulation on Physiological Activity and Golf Performance

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Description
Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has

Electrical nerve stimulation is a promising drug-free technology that could treat a variety of ailments and disorders. Methods like Vagus Nerve Stimulation have been used for decades to treat disorders like epilepsy, and research with non-invasive vagus nerve stimulation has shown similar effects as its invasive counterpart. Non-invasive nerve stimulation methods like vagus nerve stimulation could help millions of people treat and manage various disorders.

This study observed the effects of three different non-invasive nerve stimulation paradigms in human participants. The first study analyzed the safety and efficacy of transcutaneous auricular vagal nerve stimulation in healthy humans using a bilateral stimulation protocol with uniquely designed dry-hydrogel electrodes. Results demonstrate bilateral auricular vagal nerve stimulation has significant effects on specific parameters of autonomic activity and is safe and well tolerated. The second study analyzed the effects of non-invasive electrical stimulation of a region on the side of the neck that contains the Great Auricular Nerve and the Auricular Branch of the Vagus Nerve called the tympanomastoid fissure on golf hitting performance in healthy golfers. Results did not show significant effects on hitting performance or physiological activity, but the nerve stimulation had significant effects on reducing state-anxiety and improving the quality of feel of each shot. The third study analyzed the effects of non-invasive nerve stimulation of cervical nerves on the back of the neck on putting performance of yips-affected golfers. Results demonstrated that cervical nerve stimulation had significant effects on improving putting performance but did not have significant effects on physiological activity. Data from these studies show there are potential applications for non-invasive electrical nerve stimulation for healthy and athletic populations. Future research should also examine the effects of these stimulation methods in clinical populations.
Date Created
2020
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Ultrahigh Field Functional Magnetic Resonance Electrical Impedance Tomography (fMREIT) in Neural Activity Imaging

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Description
A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.

The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution

A direct Magnetic Resonance (MR)-based neural activity mapping technique with high spatial and temporal resolution may accelerate studies of brain functional organization.

The most widely used technique for brain functional imaging is functional Magnetic Resonance Image (fMRI). The spatial resolution of fMRI is high. However, fMRI signals are highly influenced by the vasculature in each voxel and can be affected by capillary orientation and vessel size. Functional MRI analysis may, therefore, produce misleading results when voxels are nearby large vessels. Another problem in fMRI is that hemodynamic responses are slower than the neuronal activity. Therefore, temporal resolution is limited in fMRI. Furthermore, the correlation between neural activity and the hemodynamic response is not fully understood. fMRI can only be considered an indirect method of functional brain imaging.

Another MR-based method of functional brain mapping is neuronal current magnetic resonance imaging (ncMRI), which has been studied over several years. However, the amplitude of these neuronal current signals is an order of magnitude smaller than the physiological noise. Works on ncMRI include simulation, phantom experiments, and studies in tissue including isolated ganglia, optic nerves, and human brains. However, ncMRI development has been hampered due to the extremely small signal amplitude, as well as the presence of confounding signals from hemodynamic changes and other physiological noise.

Magnetic Resonance Electrical Impedance Tomography (MREIT) methods could have the potential for the detection of neuronal activity. In this technique, small external currents are applied to a body during MR scans. This current flow produces a magnetic field as well as an electric field. The altered magnetic flux density along the main magnetic field direction caused by this current flow can be obtained from phase images. When there is neural activity, the conductivity of the neural cell membrane changes and the current paths around the neurons change consequently. Neural spiking activity during external current injection, therefore, causes differential phase accumulation in MR data. Statistical analysis methods can be used to identify neuronal-current-induced magnetic field changes.
Date Created
2019
Agent

Dynamic changes in heart rate and cerebral blood flow during acute vagal nerve stimulation

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Description
Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may

Vagal Nerve Stimulation (VNS) has been shown to be a promising therapeutic technique in treating many neurological diseases, including epilepsy, stroke, traumatic brain injury, and migraine headache. The mechanisms by which VNS acts, however, are not fully understood but may involve changes in cerebral blood flow. The vagus nerve plays a significant role in the regulation of heart rate and cerebral blood flow that are altered during VNS. Here, the effects of acute vagal nerve stimulation using varying stimulation parameters on both heart rate and cerebral blood flow were examined. Laser Speckle Contrast Analysis (LASCA) was used to analyze the cerebral blood flow of male Long–Evans rats. In the first experiment, results showed two distinct patterns of responses to 0.8mA of stimulation whereby animals either experienced a mild or severe decrease in heart rate. Further, animals that displayed mild heart rate decreases showed an increase in cerebral blood flow that persisted beyond VNS. Animals that displayed severe decreases showed a transient decrease in cerebral blood flow followed by an increase that was greater than that observed in mild animals but progressively decreased after VNS. The results suggest two distinct patterns of changes in both heart rate and blood flow that may be related to the intensity of VNS. To investigate the effects of lower levels of stimulation, an additional group of animals were stimulated at 0.4mA. The results showed moderate changes in heart rate but no significant changes in cerebral blood flow in these animals. The results demonstrate that VNS alters both heart rate and cerebral blood flow and that these effects are dependent on current intensity.
Date Created
2019
Agent

The Use of Brain Signals to Control a Robotic Car: A First Step

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Description
In this study, the engineers from biomedical engineering and electrical engineering researched and analyzed the components, uses, and processes for the brain and the Brain-Computer Interfaces (BCIs). They investigated the basics on the brain, the signals, and the overall uses

In this study, the engineers from biomedical engineering and electrical engineering researched and analyzed the components, uses, and processes for the brain and the Brain-Computer Interfaces (BCIs). They investigated the basics on the brain, the signals, and the overall uses of the devices. There have been many uses for electroencephalogram (EEG) signals, including prosthetics for patients after nerve injuries, cursor movements on a computer, moving vehicles, and many more projects. There are studies currently in progress and that will be in progress in the future that extend the uses of BCIs. The researchers in this thesis focused more on the processes the scientists used to approach the given problem. Some worked with patients to better his or her life, while others worked with volunteers to gain more knowledge of the brain and/or the BCIs. This thesis includes many different approaches for many unique projects. The analysis includes the location of the signal, the processing of the signal, the filtering of the signal, the transmission of the signal, and the movement of the device based on the signal. The current BCIs are not ready to be in patient’s daily lives, but the researchers are trying to create and perfect them in order to help as many patients as possible. As a biomedical engineer, the researchers in this thesis can apply the knowledge from the articles to solving potential problems in the future and further specific studies.
Date Created
2019-05
Agent

A Literature Review of the Lack of Prenatal Healthcare in Third World Countries

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Description
The dilemma of the lack of prenatal and neonatal healthcare has been prevalent among third world countries for many years. The lack of prenatal healthcare has been shown to have direct links to spontaneous preterm births from which low-birth weight

The dilemma of the lack of prenatal and neonatal healthcare has been prevalent among third world countries for many years. The lack of prenatal healthcare has been shown to have direct links to spontaneous preterm births from which low-birth weight in babies can be a result. The World Health Organization has identified preterm birth as one of the biggest overseen burdens in developing countries.
This study seeks to answer the research questions: What are the major risk factors associated with the lack of prenatal and neonatal healthcare in developing countries? What are potential routes of intervention (ROI) to help these countries? The goal is to analyze the risk factors and determine if there are any ROIs available to minimize potential incidents or accidents associated with complications of preterm birth.
A few potential risk factors include: poverty, a mother’s lack of education, a lack of professional visitation during pregnancy, having a short cervix, and routine use of Ultrasound. This research paper has identified that keeping ultrasound diagnostics to a minimum, seeking professional help during pregnancy, incorporating corticosteroids for preterm births, implementing Kangaroo Mother Care, and Cervical Cerclage are interventions that can reduce preterm births and the associated complications that come with it. We believe that further research, regarding compliance of each of these interventions, would show reduction of preterm births and low birth weight in developing countries.
Date Created
2019-05
Agent

MEMS Drug Delivery Using Pulsed Voltage Waveforms

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Description
Abstract: The delivery of a drug or gene payload inside an individual neuron has been highly sought after and studied as a means of treating a large variety of neurological diseases and disorders such as cancer and Alzheimer’s. Current

Abstract: The delivery of a drug or gene payload inside an individual neuron has been highly sought after and studied as a means of treating a large variety of neurological diseases and disorders such as cancer and Alzheimer’s. Current technology for these applications remains imperfect particularly with respect to matters of precision and cell viability. Thus, the use of MEMS (micro electro mechanical systems) based systems have become more prevalent in order to conduct these processes with higher precision and automation. Penetrating these specific cells while also maintaining their structural integrity during the process, remain as two major hurdles still being explored today. Electrical stimulation has been used to drive the delivery of a payload at the microscale but to do so with a voltage that keeps the neuron viable is imperative. In order to find a means for optimizing the voltage and ejection of the payload while maintaining cell viability, the goal of this project is to explore the use of pulsed waveforms for driving the delivery. In doing so, lower to moderate voltage amplitudes may potentially be used while also avoiding hydrolysis of the cell. This study was done by ejecting dye dextran from glass micropipettes with an agar and artificial seawater well using both DC and pulsed waveforms. Successful ejection of the payload was achieved and confirmed using fluorescent microscopy. While the methods used for this voltage based delivery require further optimization, the successful ejection utilizing pulsed voltages suggest that this may lead to an improved technique for MEMS based delivery of payloads into single cells in the future.
Date Created
2019-05
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