Biomedical Engineering and Bioengineering Commons^™

Machine Learning Methods For Medical And Biological Image Computing, Rongjian Li

Computer Science Theses & Dissertations

Medical and biological imaging technologies provide valuable visualization information of structure and function for an organ from the level of individual molecules to the whole object. Brain is the most complex organ in body, and it increasingly attracts intense research attentions with the rapid development of medical and bio-logical imaging technologies. A massive amount of high-dimensional brain imaging data being generated makes the design of computational methods for efficient analysis on those images highly demanded. The current study of computational methods using hand-crafted features does not scale with the increasing number of brain images, hindering the pace of scientific discoveries …

A 'Tissue Model' To Study The Barrier Effects Of Living Tissues On The Reactive Species Generated By Surface Air Discharge, Tongtong He, Dingxin Liu, Han Xu, Zhichao Liu, Dehui Xu, Dong Li, Qiosong Li, Mingzhe Rong, Michael G. Kong

Bioelectrics Publications

Gelatin gels are used as surrogates of human tissues to study their barrier effects on incoming reactive oxygen and nitrogen species (RONS) generated by surface air discharge. The penetration depth of nitrite into gelatin gel is measured in real time during plasma treatment, and the permeabilities of nitrite, nitrate, O₃ and H₂O₂ through gelatin gel films are quantified by measuring their concentrations in the water underneath such films after plasma treatment. It is found that the penetration speed of nitrite increases linearly with the mass fraction of water in the gelatin gels, and the permeabilities of …

Experimental Assessment Of Mouse Sociability Using An Automated Image Processing Approach, Frency Varghese, Jessica A. Burket, Andrew D. Benson, Stephen I. Deutsch, Christian W. Zemlin

Electrical & Computer Engineering Faculty Publications

Mouse is the preferred model organism for testing drugs designed to increase sociability. We present a method to quantify mouse sociability in which the test mouse is placed in a standardized apparatus and relevant behaviors are assessed in three different sessions (called session I, II, and III). The apparatus has three compartments (see Figure 1), the left and right compartments contain an inverted cup which can house a mouse (called “stimulus mouse”). In session I, the test mouse is placed in the cage and its mobility is characterized by the number of transitions made between compartments. In session II, a …

Section Abstracts: Biomedical And General Engineering

Virginia Journal of Science

Abstracts of the Biomedical and General Engineering Section for the 94th Annual Virginia Academy of Science Meeting, May 18-20, 2016, at University of Mary Washington, Fredericksburg, VA.

Membrane Channel Gene Expression In Human Costal And Articular Chondrocytes, A. Asmar, R. Barrett-Jolley, A. Werner, R. Kelly Jr., M. Stacey

Bioelectrics Publications

Chondrocytes are the uniquely resident cells found in all types of cartilage and key to their function is the ability to respond to mechanical loads with changes of metabolic activity. This mechanotransduction property is, in part, mediated through the activity of a range of expressed transmembrane channels; ion channels, gap junction proteins, and porins. Appropriate expression of ion channels has been shown essential for production of extracellular matrix and differential expression of transmembrane channels is correlated to musculoskeletal diseases such as osteoarthritis and Albers-Sch€onberg. In this study we analyzed the consistency of gene expression between channelomes of chondrocytes from human …

Non-Thermal Atmospheric-Pressure Plasma For Sterilization Of Surfaces And Biofilms, Johanna Ursula Neuber

Electrical & Computer Engineering Theses & Dissertations

Bacterial resistance to antimicrobial methods is a critical issue in many fields of medicine. This work describes the studies performed to characterize and optimize the bacterial inactivation effects of a non-thermal atmospheric-pressure plasma brush and plasma jet on a laminate surface inoculated with Acinetobacter baumannii and Staphylococcus aureus, and a cultivated Enterococcus faecalis biofilm, respectively. These treatments are pilot studies for eventual application to surface sterilization in hospitals and root canal disinfection. To evaluate bacterial inactivation, after treatment and recovery, the bacterial colony forming units (CFUs) are counted. Several different methods are used to optimize the antimicrobial effect. For the …

Effect Of Twisted Fiber Anisotropy In Cardiac Tissue On Ablation With Pulsed Electric Fields, Fei Xie, Christian W. Zemlin

Bioelectrics Publications

Background: Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart.

Methods: We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered …

Cell Electrosensitization Exists Only In Certain Electroporation Buffers, Janja Dermol, Olga N. Pakhomova, Andrei G. Pakhomov, Damijan Miklavčič

Bioelectrics Publications

Electroporation-induced cell sensitization was described as the occurrence of a delayed hypersensitivity to electric pulses caused by pretreating cells with electric pulses. It was achieved by increasing the duration of the electroporation treatment at the same cumulative energy input. It could be exploited in electroporation-based treatments such as electrochemotherapy and tissue ablation with irreversible electroporation. The mechanisms responsible for cell sensitization, however, have not yet been identified. We investigated cell sensitization dynamics in five different electroporation buffers. We split a pulse train into two trains varying the delay between them and measured the propidium uptake by fluorescence microscopy. By fitting …

Cytosolic Dna Sensor Upregulation Accompanies Dna Electrotransfer In B16.F10 Melanoma Cells, Katarina Znidar, Masa Bosnjak, Maja Cemazar, Loree C. Heller

Bioelectrics Publications

In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFN β mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16. F10 …

Analysis Of Ca²⁺ Mobilization Of Nanosecond Pulses In Cells, Iurii Semenov

Bioelectrics Publications

Exposure to nanosecond electric pulses (nsEPs) evokes transient rise of cytosolic free Ca²⁺ concentration ([Ca²⁺]i) in the cells. We quantified the external Ca²⁺ uptake, intracellular Ca²⁺ release and uncover interplay of these processes for CHO-K1 cells upon exposure to single 60 ns pulse in the range of amplitudes from 0 to 30 kV/cm. NsEPs are distinguished by the ability to electroporate intracellular membranes. We studied how duration of nsEPs is related to efficiency of intracellular membranes electroporation comparing ability of single 300-, 60- and 10 ns pulses to recruit Ca²⁺ from endoplasmic reticulum (ER) in respect to the uptake of …

Activation Of Dna Pattern Recognition Receptors After Plasmid Electrotransfer In Melanoma Cells And Tumors, Loree Heller, Masa Bosnjak, Katarina Znidar, Maja Cemazar

Bioelectrics Publications

(First sentence) In vivo electroporation or electrotransfer, the application of controlled electric pulses, enhances delivery of plasmid DNA to a wide variety of healthy tissues as well as tumor types.

Computational Assessment Of Neural Probe And Brain Tissue Interface Under Transient Motion, Michael Polanco, Sebastian Bawab, Hangsoon Yoon

Mechanical & Aerospace Engineering Faculty Publications

The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial …

Anticancer, Biophysical And Computational Investigations Of Half-Sandwich Ruthenium(Ii) Thiosemicarbazone Complexes: The Effect Of Arene Versus Thiacrown Face-Cap, Floyd A. Beckford, Alyssa Stott, P. Canisius Mbarushimana, Marc-Andre Leblanc, Kinsey Hall, Samantha Smith, Jimmie L. Bullock, Dennis J. Houghton, Alvin A. Holder, Nikolay Gerasimchuk, Antonio Gonzalez-Sarrías

Chemistry & Biochemistry Faculty Publications

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10 …

A Microfluidic-Based Tactile Sensor For Palpating Mice Tumor Tissues, Yichao Yang, Garett Johnson, Dean Krusienski, Siqi Guo, Cheng Lin, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

In light of the need of tissue palpation for Robotics-assisted Minimally Invasive Surgery (RMIS), this paper presents a microfluidic-based tactile sensor for palpating mice tissues for tumor localization. The core of the sensor is a 3x3 sensing-plate/transducer array built into a single polydimethylsiloxane (PDMS) microstructure, with a transducer spacing of 3.75mmx1.5mm. Mounted on a robot, the sensor is pressed against a tissue region with a pre-defined indentation depth pattern, and consequently the stiffness distribution across the tissue region translates to the deflection distribution of the sensing-plate array and is captured by the transducer array underneath as resistance changes. Thus, the …

A Flexible Pet-Based Wearable Sensor For Arterial Pulse Waveform Measurement, Dan Wang, Dean Krusienski, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

In light of the need of health monitoring, the paper presents a flexible polyethylene terephthalate (PET)-based wearable sensor for arterial pulse waveform measurement. The sensor encompasses a polydimethylsiloxane (PDMS) microstructure embedded with an electrolyte-enabled 5×1 transducer array, which spans 6mm and has a spatial resolution of 1.5mm. A pulse signal exerts a deflection on the microstructure and is recorded as a resistance change by a transducer at the site of the pulse. An untrained individual can easily align the sensor on a targeted artery with a negligible margin and then acquire the arterial pulse waveform continuously and non-invasively. This sensor …

Radio-Frequency Plasma Polymerized Biodegradable Carrier For In Vivo Release Of Cis-Platinum, Sudhir Bhatt, Fatemeh Valamanesh, Jerome Pulpytel, Rea Lo Dico, Aliby Baiyukha, Iman Al-Dybiat, Marc Pocard, Farzaneh Arefi-Khonsari, Massoud Mirshahi

Bioelectrics Publications

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm²) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of …

Impairment Of Continuous Insulin Delivery Therapy And Analysis From Graeco-Latin Square Design Model, Norou Diawara, Ayodeji Demuren, Eric Gyuricsko

Mathematics & Statistics Faculty Publications

The desire to deliver measured amount of insulin continuously to patients with type I diabetes, for glycemic control, has attracted a lot of attention. Continuous subcutaneous insulin infusion has seen some success in recent years. However, occlusion of insulin delivery may prevent the patient from receiving the prescribed dosage, with adverse consequence. An in vitro study of insulin delivery is performed, using different insulin pumps, insulin analogs and operating conditions. The aim is to identify incidences of occlusion due to bubble formation in the infusion line. A detailed statistical analysis was performed on the data collected to determine any significant …

Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …

Modeling Early Stage Bone Regeneration With Biomimetic Electrospun Fibrinogen Nanofibers And Adipose-Derived Mesenchymal Stem Cells, Michael P. Francis, Yas M. Moghaddam-White, Patrick C. Sachs, Matthew J. Beckman, Stephen M. Chen, Gary L. Bowlin, Lynne W. Elmore, Shawn E. Holt

School of Medical Diagnostics & Translational Sciences Publications

The key events of the earliest stages of bone regeneration have been described in vivo although not yet modeled in an in vitro environment, where mechanistic cell-matrix-growth factor interactions can be more effectively studied. Here, we explore an early-stage bone regeneration model where the ability of electrospun fibrinogen (Fg) nanofibers to regulate osteoblastogenesis between distinct mesenchymal stem cells populations is assessed. Electrospun scaffolds of Fg, polydioxanone (PDO), and a Fg:PDO blend were seeded with adipose-derived mesenchymal stem cells (ASCs) and grown for 7-21 days in osteogenic differentiation media or control growth media. Scaffolds were analyzed weekly for histologic and molecular …

Accessible Bioprinting: Adaptation Of A Low-Cost 3d-Printer For Precise Cell Placement And Stem Cell Differentiation, John A. Reid, Peter A. Mollica, Garett D. Johnson, Roy C. Ogle, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the-shelf' commercially available 3D printer. We also demonstrate via goal based …

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda J. Ashdown, Mark W. Scerbo, Lee A. Belfore Ii, Stephen S. Davis, Alfred Z. Abuhamad

Psychology Faculty Publications

Objective This study examined the ability of clinicians to correctly categorize images of fetal heart rate (FHR) variability with and without the use of exemplars.

Study Design A sample of 33 labor and delivery clinicians inspected static FHR images and categorized them into one of four categories defined by the National Institute of Child Health and Human Development (NICHD) based on the amount of variability within absent, minimal, moderate, or marked ranges. Participants took part in three conditions: two in which they used exemplars representing FHR variability near the center or near the boundaries of each range, and a third …

The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin

Bioelectrics Publications

The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …

Effects Of High Voltage Nanosecond Electric Pulses On Eukaryotic Cells (In Vitro): A Systematic Review, Tina Batista Napotink, Matej Reberšek, P. Thomas Vernier, Babara Mali, Damijan Miklavčič

Bioelectrics Publications

For this systematic review, 203 published reports on effects of electroporation using nanosecond high-voltage electric pulses (nsEP) on eukaryotic cells (human, animal, plant) in vitro were analyzed. A field synopsis summarizes current published data in the field with respect to publication year, cell types, exposure configuration, and pulse duration. Published data were analyzed for effects observed in eight main target areas (plasma membrane, intracellular, apoptosis, calcium level and distribution, survival, nucleus, mitochondria, stress) and an additional 107 detailed outcomes. We statistically analyzed effects of nsEP with respect to three pulse duration groups: A: 1–10 ns, B: 11–100 ns and C: …

Nanosecond Pulsed Platelet-Rich Plasma (Nsprp) Improves Mechanical And Electrial Cardiac Function Following Myocardial Reperfusion Injury, Barbara Y. Hargrave, Frency Varghese, Nektarios Barabutis, John Catravas, Christian Zemlin

School of Medical Diagnostics & Translational Sciences Publications

Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial …

Spatio-Temporal Progression Of Cortical Activity Related To Continuous Overt And Covert Speech Production In A Reading Task, Jonathan S. Brumberg, Dean J. Krusienski, Shreya Chakrabarti, Aysegul Gunduz, Peter Brunner, Anthony L. Ritaccio, Gerwin Schalk

Electrical & Computer Engineering Faculty Publications

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded …

New Engineering Approaches To Arrhythmias And Myocardial Infarction, Frency Varghese

Biomedical Engineering Theses & Dissertations

In this thesis, we present new engineering approaches to several important cardiac diseases. Chapter 1 considers the dynamics of arrhythmias. The most dangerous arrhythmias are reentrant arrhythmias, including ventricular fibrillation and ventricular tachycardia. During these arrhythmias, there are one or several rotating excitation waves present in the heart. Because of their shape, these waves are called scroll waves; their center of rotation is a one-dimensional curve called the filament. Filaments largely constrain the configuration of a scroll wave but are much simpler, so much effort has gone into describing scroll wave dynamics in terms of the dynamics of their filaments. …

Mobile Cloud Computing Based Non Rigid Registration For Image Guided Surgery, Arun Brahmavar Vishwanatha

Computer Science Theses & Dissertations

In this thesis we present the design and implementation of a Mobile Cloud computing platform for non-rigid registration required in Image Guided Surgery (MCIGS). MCIGS contributes in flexible, portable and accurate alignment of pre-operative brain data with intra-operative MRI, for image guided diagnosis and therapy and endoscopic skull base surgery. Improved precision of image guided therapy and specifically neurosurgery procedures is known to result in the improved prognosis for brain tumor patients. MCI GS system is tested with Physics Based Non-Rigid Registration method form ITK. Our preliminary results for brain images indicate that the proposed system over Wi-Fi can be …

Nanosecond Pulse Electric Field Activated-Platelet Rich Plasma Enhances The Return Of Blood Flow To Large And Ischemic Wounds In A Rabbit Model, Barbara Y. Hargrave, Francis Li

Bioelectrics Publications

Platelet-rich plasma is a therapeutic strategy used for accelerating wound healing of a wide range of tissues through the release of platelet growth factors. Here, we describe a nonchemical, safe method for preparing platelet-rich plasma using nanosecond-pulsed electric fields (nsPEFs) and investigated the effect of this platelet-rich plasma on reperfusion of blood in large skin flap or ischemic hind limb wounds in New Zealand White rabbits. Laser Doppler images of blood flow to the dorsal surface of skin flap wounds or to ischemic hind limb wounds were obtained from wounds treated with 0.9% saline or nanosecond-pulsed electric field prepared platelet-rich …

The Effect Of Posterior Foot Positions On Electromyography, Joint Kinetics And Energetics During A Sit-To-Stand In Young And Older Adults, Eric A. Pitman

Human Movement Studies & Special Education Theses & Dissertations

The sit-to-stand (STS) movement, defined as standing up from a chair to an upright posture, is a common task performed daily. The inability to accomplish this task may lead to dependence, institutionalization and even death in older adults. A common strategy change for the STS is positioning the feet posteriorly by increasing flexion at the knee joint. This reduces the displacement of the center of mass to the base of support while increasing the joint moment of force at the knee while decreasing it at the hip. The aims of this study were to: 1) examine the joint kinetics, joint …

Nano Scale Mechanical Analysis Of Biomaterials Using Atomic Force Microscopy, Diganta Dutta

Mechanical & Aerospace Engineering Theses & Dissertations

The atomic force microscope (AFM) is a probe-based microscope that uses nanoscale and structural imaging where high resolution is desired. AFM has also been used in mechanical, electrical, and thermal engineering applications. This unique technique provides vital local material properties like the modulus of elasticity, hardness, surface potential, Hamaker constant, and the surface charge density from force versus displacement curve. Therefore, AFM was used to measure both the diameter and mechanical properties of the collagen nanostraws in human costal cartilage. Human costal cartilage forms a bridge between the sternum and bony ribs. The chest wall of some humans is deformed …