Matching Items (76)
Description
Tracking microscale targets in soft tissue using implantable probes is important in clinical applications such as neurosurgery, chemotherapy and in neurophysiological application such as brain monitoring. In most of these applications, such tracking is done with visual feedback involving some imaging modality that helps localization of the targets through images that are co-registered with stereotaxic coordinates. However, there are applications in brain monitoring where precision targeting of microscale targets such as single neurons need to be done in the absence of such visual feedback. In all of the above mentioned applications, it is important to understand the dynamics of mechanical stress and strain induced by the movement of implantable, often microscale probes in soft viscoelastic tissue. Propagation of such stresses and strains induce inaccuracies in positioning if they are not adequately compensated. The aim of this research is to quantitatively assess (a) the lateral propagation of stress and (b) the spatio-temporal distribution of strain induced by the movement of microscale probes in soft viscoelastic tissue. Using agarose hydrogel and a silicone derivative as two different bench-top models of brain tissue, we measured stress propagation during movement of microscale probes using a sensitive load cell. We further used a solution of microscale beads and the silicone derivative to quantitatively map the strain fields using video microscopy. The above measurements were done under two different types of microelectrode movement – first, a unidirectional movement and second, a bidirectional (inch-worm like) movement both of 30 μm step-size with 3min inter-movement interval. Results indicate movements of microscale probes can induce significant stresses as far as 500 μm laterally from the location of the probe. Strain fields indicate significantly high levels of displacements (in the order of 100 μm) within 100 μm laterally from the surface of the probes. The above measurements will allow us to build precise mechanical models of soft tissue and compensators that will enhance the accuracy of tracking microscale targets in soft tissue.
ContributorsTalebianmoghaddam, Shahrzad (Author) / Muthuswamy, Jitendran (Thesis advisor) / Towe, Bruce (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2015
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 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.
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.
ContributorsAshok Kumar, Neeta (Author) / Sadleir, Rosalind J (Thesis advisor) / Greger, Bradley (Committee member) / Muthuswamy, Jitendran (Committee member) / Tillery, Stephen H (Committee member) / Sohn, SungMin (Committee member) / Arizona State University (Publisher)
Created2020
Description
Transcranial focused ultrasound (tFUS) is a unique neurostimulation modality with potential to develop into a highly sophisticated and effective tool. Unlike any other noninvasive neurostimulation technique, tFUS has a high spatial resolution (on the order of millimeters) and can penetrate across the skull, deep into the brain. Sub-thermal tFUS has been shown to induce changes in EEG and fMRI, as well as perception and mood. This study investigates the possibility of using tFUS to modulate brain networks involved in attention and cognitive control.Three different brain areas linked to saliency, cognitive control, and emotion within the cingulo-opercular network were stimulated with tFUS while subjects performed behavioral paradigms. The first study targeted the dorsal anterior cingulate cortex (dACC), which is associated with performance on cognitive attention tasks, conflict, error, and, emotion. Subjects performed a variant of the Erikson Flanker task in which emotional faces (fear, neutral or scrambled) were displayed in the background as distractors. tFUS significantly reduced the reaction time (RT) delay induced by faces; there were significant differences between tFUS and Sham groups in event related potentials (ERP), event related spectral perturbation (ERSP), conflict and error processing, and heart rate variability (HRV).
The second study used the same behavioral paradigm, but targeted tFUS to the right anterior insula/frontal operculum (aIns/fO). The aIns/fO is implicated in saliency, cognitive control, interoceptive awareness, autonomic function, and emotion. tFUS was found to significantly alter ERP, ERSP, conflict and error processing, and HRV responses.
The third study targeted tFUS to the right inferior frontal gyrus (rIFG), employing the Stop Signal task to study inhibition. tFUS affected ERPs and improved stopping speed. Using network modeling, causal evidence is presented for rIFG influence on subcortical nodes in stopping.
This work provides preliminarily evidence that tFUS can be used to modulate broader network function through a single node, affecting neurophysiological processing, physiologic responses, and behavioral performance. Additionally it can be used as a tool to elucidate network function. These studies suggest tFUS has the potential to affect cognitive function as a clinical tool, and perhaps even enhance wellbeing and expand conscious awareness.
The second study used the same behavioral paradigm, but targeted tFUS to the right anterior insula/frontal operculum (aIns/fO). The aIns/fO is implicated in saliency, cognitive control, interoceptive awareness, autonomic function, and emotion. tFUS was found to significantly alter ERP, ERSP, conflict and error processing, and HRV responses.
The third study targeted tFUS to the right inferior frontal gyrus (rIFG), employing the Stop Signal task to study inhibition. tFUS affected ERPs and improved stopping speed. Using network modeling, causal evidence is presented for rIFG influence on subcortical nodes in stopping.
This work provides preliminarily evidence that tFUS can be used to modulate broader network function through a single node, affecting neurophysiological processing, physiologic responses, and behavioral performance. Additionally it can be used as a tool to elucidate network function. These studies suggest tFUS has the potential to affect cognitive function as a clinical tool, and perhaps even enhance wellbeing and expand conscious awareness.
ContributorsFini, Maria Elizabeth (Author) / Tyler, William J (Thesis advisor) / Greger, Bradley (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2020
Biomechanical Micromotion at the Neural Interface Modulates Intercellular Membrane Potential In-Vivo
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 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.
ContributorsDuncan, Jonathan Leroy (Author) / Muthuswamy, Jitendran (Thesis advisor) / Greger, Bradley (Committee member) / Sridharan, Arati (Committee member) / Arizona State University (Publisher)
Created2020
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 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.
ContributorsMoghadas, Babak (Author) / Kodibagkar, Vikram D (Thesis advisor) / Beeman, Scott (Committee member) / Muthuswamy, Jitendran (Committee member) / Nikkhah, Mehdi (Committee member) / Turner, Gregory (Committee member) / Arizona State University (Publisher)
Created2021
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 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.
ContributorsKerlee, Jessica (Author) / Rodriguez, Armando (Thesis director) / Muthuswamy, Jitendran (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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 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.
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.
ContributorsHuapaya, Eduardo Luciano (Author) / Muthuswamy, Jitendran (Thesis director) / Comar, William (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Piloerection (known as goosebumps) is mediated by activation of alpha-adrenergic receptors within the sympathetic branch of the autonomic nervous system. The study of piloerection is important in multiple fields, from emotion studies to nervous system pathology. This makes piloerection particularly relevant to emotions research. Despite wide-ranging applications, current methods for measuring piloerection are laborious and qualitative. The goal of this study is to build a wearable piloerection sensor through the use of straight-line lasers and photoresistors. The study analyzed methods of detecting and measuring goosebumps, and applied the method of laser scattering as a detection method. This device was designed and tested against a population of seven Arizona State University students. Goosebumps were elicited through conditions of cold, and video clips meant to elicit emotions of awe and sadness. Piloerection was then quantified through two controls of self-identification and camera recording, as well as the new detection method. These were then compared together, and it was found that subjective methods of determining goosebumps did not correlate well with objective measurements, but that the two objective measurements correlated well with one another. This shows that the technique of laser scattering can be used to detect goosebumps and further developments on this new detection method will be made. Moreover, the presence of uncorrelated subjective measurements further shows the need for an objective measurement of piloerection, while also bringing into question other factors that may be confused with the feeling of piloerection, such as chills or shivers. This study further reaffirmed previous studies showing a positive correlation between intense emotions.
ContributorsHemesath, Angela (Author) / Muthuswamy, Jitendran (Thesis director) / Shiota, Michelle (Lani) (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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 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.
ContributorsStamm, Steven Jeffrey (Author) / Muthuswamy, Jitendran (Thesis director) / Sridharan, Arati (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Interictal spikes have been used to diagnose idiopathic seizure disorder and localize the seizure onset zone. Interictal spikes are thought to arise primarily from large excitatory postsynaptic potentials, and the role of interictal spikes in idiopathic seizure disorder and epileptogenesis remains unclear. We evaluated how local voltage changes due to interictal spikes impact action potential generation and firing using intracellular recordings from human tissue and the Hodgkin-Huxley model. During interictal spikes, bursts of action potentials underwent variable degrees of depolarization-induced inactivation in the intracellular data. Intracellular recordings in neocortical slices of human brain tissue confirmed that bursts of inactivated action potentials occurred during spontaneous paroxysmal depolarization shifts. These ex vitro findings were predicted using the Hodgkin-Huxley model and showed inactivated action potentials being generated by large depolarizations. As the amplitude of the interictal spike increased, there was a progression from low firing rate normal action potentials to higher firing rate normal action potentials to inactivated action potentials. The results show that the Hodgkin-Huxley model confirmed the effect of large interictal spike depolarizations on action potential firing and inactivation. This supports a key element in the hypothesis that interictal spikes, and the associated action potential firing, may alter the electrical environment of the brain and contribute to idiopathic seizure disorder.
ContributorsLossner, Lauren Nicole (Author) / Greger, Bradley (Thesis director) / Foldes, Stephen (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12