Bioelectrical and Neuroengineering Commons^™

Pulsed Electric Field Ablation Of Esophageal Malignancies And Mitigating Damage To Smooth Muscle: An In Vitro Study, Emily Gudvangen, Uma Mangalanathan, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Andrei G. Pakhomov

Bioelectrics Publications

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca²⁺ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them …

Measurement Of Fluid Movement Throughout The Brain Via Multiple Magnetic Resonance Imaging Techniques During High-Definition Transcranial Direct Current Stimulation, Jack W. Beaty Mr

Dissertations and Theses

Transcranial Direct Current Stimulation (tDCS) is a non-invasive method of neuromodulation with applications in neuroscience, clinical care, and biomedical engineering. tDCS has been well established as a safe method of applying low amplitude current between two or more electrodes to alter excitation thresholds and neuroplasticity. Recently, in-vitro and clinical studies have suggested that DC stimulation can induce a transient, polarity-specific, effect of increased water exchange across the blood-brain barrier (BBB). The electroosmotic effect, the proposed phenomenon driving water exchange, is a biophysical response of charged ions moving across an oppositely-charged surface, i.e., the tight junction, when subjected to an electric …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

Emulating Future Neurotechnology Using Magic, Jay A. Olson, Mariève Cyr, Despina Z. Artenie, Thomas Strandberg, Lars Hall, Matthew L. Tompkins, Amir Raz, Petter Johansson

Psychology Faculty Articles and Research

Recent developments in neuroscience and artificial intelligence have allowed machines to decode mental processes with growing accuracy. Neuroethicists have speculated that perfecting these technologies may result in reactions ranging from an invasion of privacy to an increase in self-understanding. Yet, evaluating these predictions is difficult given that people are poor at forecasting their reactions. To address this, we developed a paradigm using elements of performance magic to emulate future neurotechnologies. We led 59 participants to believe that a (sham) neurotechnological machine could infer their preferences, detect their errors, and reveal their deep-seated attitudes. The machine gave participants randomly assigned positive …

The Influence Of Electrical Stimulation Pulse Frequency Of Macro-Sieve Electrode On Rat Sciatic Nerve Detection Threshold, Jingyuan Zhang

McKelvey School of Engineering Theses & Dissertations

No abstract provided.

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Optimization Of A Novel Barnes Maze Protocol For Assessing Antioxidant Treatment Of Traumatic Brain Injury, Connor C. Gee

Biological Systems Engineering--Dissertations, Theses, and Student Research

Current preclinical research into traumatic brain injury focuses heavily upon cellular and molecular testing to determine the effects of injury and potential benefits of neuroprotective treatments. While this may be a useful method, some argue that an increased focus on behavioral testing could lead to better clinical translation as these assays assess the longer term, downstream effects from a brain injury. The most characterized behavioral tests used in traumatic brain injury research are the spatial learning and memory paradigms, Morris Water Maze and Barnes Maze. The Morris Water Maze is the most used of theses paradigms and relies on spatial …

Application Of Neural Networks To Predict Patient-Specific Cellular Parameters In Computational Cardiac Models, Chang Hi Lee

McKelvey School of Engineering Theses & Dissertations

Sudden cardiac death(SCD) is a significant cause of death that accounts for more than 180,000 deaths in the US and 4 million deaths worldwide annually. SCDs are mainly caused by irregular heartbeats called arrhythmias, which are caused by abnormal electrical activity within the heart. Precision medicine, in the form of personalized computational cardiac models of a patient’s heart, can suggest optimal therapies for cardiac arrhythmias. Prior work has used finite element meshes derived from cardiac MRIs to simulate cardiac electrical activity. In this study, I sought to augment this approach by developing a neural network to learn the parameters that …

Closed-Loop Brain-Computer Interfaces For Memory Restoration Using Deep Brain Stimulation, David Xiaoliang Wang

Electrical Engineering Theses and Dissertations

The past two decades have witnessed the rapid growth of therapeutic brain-computer interfaces (BCI) targeting a diversity of brain dysfunctions. Among many neurosurgical procedures, deep brain stimulation (DBS) with neuromodulation technique has emerged as a fruitful treatment for neurodegenerative disorders such as epilepsy, Parkinson's disease, post-traumatic amnesia, and Alzheimer's disease, as well as neuropsychiatric disorders such as depression, obsessive-compulsive disorder, and schizophrenia. In parallel to the open-loop neuromodulation strategies for neuromotor disorders, recent investigations have demonstrated the superior performance of closed-loop neuromodulation systems for memory-relevant disorders due to the more sophisticated underlying brain circuitry during cognitive processes. Our efforts are …

Fabrication Of Hydrogel Microparticles For Acute Treatment Of Penetrating Brain Injuries, Isabell Foulger

All Theses

Traumatic brain injuries (TBIs) are a type of acquired head trauma that results from an external force to the head. The development and severity of the secondary injury increases the risk of neurodegeneration and reduced cognitive recovery. Glucocorticoids are potent antiinflammatory therapeutics that have been investigated for potential treatment of TBIs, strokes, and other neuroinflammatory pathologies. However, their clinical application has been limited due to their ability to induce a variety of side effects, including adrenal suppression, edema, and reduced plasticity of the hippocampus. The use of a localized drug delivery system would overcome these systemic concerns. In previous studies, …

Solution Of Fractional Order Differential Equation Problems By Triangular Functions For Biomedical Applications, Anish Majumder, Nilotpal Chakraborty, Kisalaya Chakrabarti, Anindita Ganguly

International Journal of Computer and Communication Technology

Abstract—Fractional Order Differential equations are used for modelling of a wide variety of biological systems but the solution process of such equations are quite complex. In this paper Orthogonal Triangular functions and their operational matrices have been used for finding an approximate solution of Fractional Order Differential Equations. This technique has been found to be more powerful in solving Fractional Order Differential Equations owing to the fact that the differential equations are reduced to systems of algebraic equations which are easy to solve numerically and the percentage error is lower compared to other methods of solutions (like: Laplace Transform Method). …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

Innovative Techniques Of Neuromodulation And Neuromodeling Based On Focal Non-Invasive Transcranial Magnetic Stimulation For Neurological Disorders, Ivan C. Carmona-Tortolero

Theses and Dissertations

This dissertation aims to develop alternative technology that improves the current range of application of transcranial magnetic stimulation (TMS), on a scale that would permit defining specific non-invasive treatments for Parkinson’s disease and other neurological disorders. This is accomplished through three specific objectives. 1) The design of a neurostimulation system that increases the focality in TMS to regions of narrow target areas and variable depths in the brain cortex. 2) The assessment of the feasibility of novel high-frequency neuromodulation techniques that would allow increasing the focality in deeper areas beyond the cortical surface. 3) The development of a computational model …

A Measurement System For Detection Of Intestinal Motility In Neonates By Monitoring Slow Wave Activity, Garett Goodale

Electronic Theses and Dissertations, 2020-

Similar to how electrocardiographic waves are the pace making signals of the heart, slow waves are the pace making signals of the intestines. Slow waves are electrical signals in the intestines that determine the speed at which food can move through the intestine ensuring proper digestion and uptake of nutrients. It has been shown that slow waves can be measured in adults using non-invasive, surface electrodes. However, no study has investigated the measurements of slow waves in neonates, specifically pre-term neonates. Around 7% of pre-term neonates suffer from necrotizing enterocolitis (NEC) which is a condition that causes damage to the …

In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar

Bioelectrics Publications

Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of …

Electroporation And Cell Killing By Milli- To Nanosecond Pulses And Avoiding Neuromuscular Stimulation In Cancer Ablation, Emily Gudvangen, Vitalii Kim, Vitalij Novickij, Federico Battista, Andrei G. Pakhomov

Bioelectrics Publications

Ablation therapies aim at eradication of tumors with minimal impact on surrounding healthy tissues. Conventional pulsed electric field (PEF) treatments cause pain and muscle contractions far beyond the ablation area. The ongoing quest is to identify PEF parameters efficient at ablation but not at stimulation. We measured electroporation and cell killing thresholds for 150 ns–1 ms PEF, uni- and bipolar, delivered in 10- to 300-pulse trains at up to 1 MHz rates. Monolayers of murine colon carcinoma cells exposed to PEF were stained with YO-PRO-1 dye to detect electroporation. In 2–4 h, dead cells were labeled with propidium. Electroporation and …

The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas

Bioelectrics Publications

Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and …

Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression And Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury In K18-Hace2 Transgenic Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, John D. Catravas

Bioelectrics Publications

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome. and increasing mortality. To investigate the mechanisms behind this interaction, we developed a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and are kept on an …

The Paradox Of Pulmonary Vascular Resistance: Restoration Of Pulmonary Capillary Recruitment As A Sine Qua Non For True Therapeutic Success In Pulmonary Arterial Hypertension, David Langleben, Stylianos E. Orfanos, Benjamin D. Fox, Nathan Messas, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension …

Low-Intensity Ultrasonic Neuromodulation Of The Rat Hippocampus, Duc Nguyen

Dissertations and Theses

Techniques to non-invasively modulate brain activity are important for mapping human brain circuits, and also for the treatment of a host of neurological and psychiatric disorders marked by aberrant brain activity. Though a wide range of techniques for non-invasive neuromodulation have been proposed, the conventional approaches suffer from significant limitations. Most notably, focal stimulation of deep brain regions is presently only possible with invasive optogenetic and chemogenetic approaches that require craniotomies and genetic access to the brain.

Transcranial focused ultrasound stimulation (tFUS) possesses many of the characteristics desirable from a neuromodulation approach: non-invasiveness, a spatial resolution in the order of …