Biomedical Engineering and Bioengineering Commons^™

Real-Time Ultrasound Simulation For Medical Training And Standardized Patient Assessment, Bo Sun

Computational Modeling & Simulation Engineering Theses & Dissertations

With the increasing role played by ultrasound in clinical diagnostics, ultrasound training in medical education has become more and more important. The clinical routine for ultrasound training is on real patients; therefore monitored and guided examinations involving medical students are quite time-constrained. Furthermore, standardized patients (SPs), who are increasingly used in medical school for teaching and assessing medical students, need to be augmented. These SPs are typically healthy individuals who can not accurately portray the variety of abnormalities that are needed for training especially when medical examinations involve instrument interactions. To augment SPs in a realistically effective way and also …

Caffeine Model Identification For Vigilance Performance Prediction, Chun-Hui Huang

Mechanical & Aerospace Engineering Theses & Dissertations

The pharmacodynamics and pharmacokinetics of caffeine have been well characterized. In this study, a caffeine dynamic model is developed to describe its pharmacodynamic effects on vigilance performance. Validated biomathematical models developed to address both individual and group fatigue and alertness in a non-laboratory setting represent a tremendous commercial opportunity. First, a test data set with caffeine effects isolated from circadian and homeostatic effects is created. Then a modeling approach for input and output effects is developed and different model structures for the caffeine effects are considered. Observer/Kalman filter Identification (OKID) algorithm is proposed and developed to identify the caffeine model …

An Approach To Identifying The Biomechanical Differences Between Intercostal Cartilage In Subjects With Pectus Excavatum And Normals In Vivo: Reconstruction And Ct Registration, Zhenzhen Yan

Electrical & Computer Engineering Theses & Dissertations

Pectus excavatum (PE) is a congenital chest wall deformity affecting the ribs and sternum and exhibiting a concave appearance in the anterior chest wall. In this thesis, we describe a study to investigate in vivo differences in the pectus excavatum rib cage and outline steps using normals and pectus patients data in developing models and methods to be used in carrying out the study. We propose methods to develop reconstructed models in order to enable proper registration between data collection points (DCPs) on the 3D CT rib cage model and CT skin surface model and registration between CT surrogate models …

The Application Of Innovative High-Throughput Techniques To Serum Biomarker Discovery, Izabela Debkiewicz Karbassi

Theses and Dissertations in Biomedical Sciences

Time-of-flight mass spectrometry continues to evolve as a promising technique for serum protein expression profiling and biomarker discovery. As seen in our initial SELDI-TOF MS and MALDI-TOF MS profiling study of serum for the assessment of breast cancer risk, many profiling strategies typically employ single chemical affinity beads or surfaces to decrease sample complexity of dynamic fluids like serum. However, most proteins, captured on a particular surface or bead, are not resolved in the lower mass range where mass spectrometers are most effective. To this end we have designed an expression profiling workflow that utilizes immobilized trypsin paramagnetic beads in …

Stochastic Calculations For Computation Of Radiation Effects And Cell Survivability Under Voltage Pulsing, Madhuri Ganapathiraju

Electrical & Computer Engineering Theses & Dissertations

Statistical computations are an important tool for the analysis of stochastic phenomena and processes that are characterized by variability. Biological systems (e.g., cells, tissues etc.) are perfect examples wherein response to a given external stimulus can be varied and needs to be adequately considered. The Monte Carlo method of analysis has now been recognized as the most effective way of treating stochastic variability.

This thesis uses Monte Carlo based simulations to probe two problems that require the quantification and modeling of effects caused by energy deposition onto biological matter from external sources. One problem involves the probabilistic study of the …

Bactericidal Effects Of Cold Plasma Technology On Geobacillus Stearothermophilus And Bacillus Cereus Microorganisms, Angela D. Morris, Gayle B. Mccombs, Susan L. Tolle, Mounir Laroussi, Wayne L. Hynes

Dental Hygiene Faculty Publications

Cold plasma is a state of matter that contains a large number of particles that are electrically charged. Plasmas generate chemically reactive species and ultraviolet radiation making them useful in decontamination applications (Kong & Laroussi, 2003). Research regarding the inactivation of gram-positive bacteria by cold plasma has been studied by Laroussi et al (2003); however, there is limited research regarding the germicidal effectiveness of cold plasma on Geobacillus stearothermophilus and Bacillus cereus microorganisms. The purpose of this study was to determine if cold plasma technology inactivates Geobacillus stearothermophilus and Bacillus cereus vegetative cells and spores. This study consisted of 981 …

Microfabrication Of An Optical Chamber For Exposing Living Cells To Pulsed Electric Fields, Saleh Sheikh

Electrical & Computer Engineering Theses & Dissertations

I have fabricated a chamber which enables the application of Nanosecond Pulsed Electric Fields (nsPEFs) to living cells while monitoring their real time fluorescence with an inverted microscope. The No. I thickness (150µm nominal) coverslip glass substrate used for fabrication allows the use of high numerical aperture oil immersion objectives for imaging intracellular organelles. Electrodes are fabricated by first evaporating a chromium adhesion layer, followed by a nickel seed layer. Subsequently, an ultra-thick positive photoresist is applied and patterned to create a 30µm thick electroplating mold. The electrodes are then electrodeposited into the mold from a nickel sulfamate plating bath. …

Simulations Of Intracellular Calcium Release In Response To High-Intensity, Ultrashort Electric Pulse, Anh Nguyen

Electrical & Computer Engineering Theses & Dissertations

Calcium modulation is an important signaling process and could even contribute to cell apoptosis through ionic-induced perturbations in trans-membrane potential at the mitochondria. In this research, the numerical study constitutes a first step in quantitatively probing the time- and spatially-dependent modulation of calcium dynamics through the application of external electrical fields. The research uses both widely accepted deterministic continuum and discrete stochastic intracellular calcium models coupling with external electric field, with a focus on high-intensity ultrashort pulse electrical field.

For deterministic continuum intracellular calcium models with electric field assisted, numerical simulations for electrically induced, intra-cellular calcium-release from the endoplasmic reticulum …

Molecular Dynamics Simulations To Probe Effects Of Ultra-Short, Very-High Voltage Pulses On Cells, Viswanadham Sridhara

Electrical & Computer Engineering Theses & Dissertations

The use of very high electric fields (∼ 100kV/cm or higher) with pulse durations in the nanosecond range (Ultra-short) has been a very recent development in bioelectrics. Traditionally, the electric field effects have mostly been confined to: (a) low field, long-duration pulses, and (b) focused mainly on electroporation studies. Thus, aspects such as possible field-induced DNA damage, calcium release, alterations in neuro-transmitters, or voltage-gating have generally been overlooked.

Ultra-short, high-field pulses open the way to targeted and deliberate apoptotic cell killing (e.g., of tumor cells). Though experimental data is very useful, it usually yields information on macroscopic variables that is …

Simulations Of Intracellular Calcium Release Dynamics In Response To A High-Intensity, Ultrashort Electric Pulse, R. P. Joshi, A. Nguyen, V. Sridhara, Q. Hu, R. Nuccitelli, Stephen J. Beebe, J. Kolb, Karl H. Schoenbach

Bioelectrics Publications

Numerical simulations for electrically induced, intracellular calcium release from the endoplasmic reticulum are reported. A two-step model is used for self-consistency. Distributed electrical circuit representation coupled with the Smoluchowski equation yields the ER membrane nanoporation for calcium outflow based on a numerical simulation. This is combined with the continuum Li-Rinzel model and drift diffusion for calcium dynamics. Our results are shown to be in agreement with reported calcium release data. A modest increase (rough doubling) of the cellular calcium is predicted in the absence of extra-cellular calcium. In particular, the applied field of 15 kV/cm with 60 ns pulse duration …

Simulation And Modeling Of Nerve Impulse Propagation And Its Blockage By External Electrical Stimulation, Nidhi Nahar

Electrical & Computer Engineering Theses & Dissertations

The electric nature of biological tissues permits the transmission of signals for information and for control and is, therefore, of vital importance for life. The latest scientific achievements and nanoscale probing techniques now allow scientists to research at the subcellular level by measuring the electric current flows through a single ion channel of the cell membrane with the patch-clamp method. With the latter approach, the effects of electrical stimulation can be quantified, understood, and applied to molecular biology and the development of medical diagnostic and therapeutic methods.

In this thesis, the Hodgkin-Huxley approach for unmyelinated fibers, coupled with a transmission …

Bioelectric Effects Of Intense Nanosecond Pulses, Karl H. Schoenbach, Barbara Y. Hargrave, Ravindra P. Joshi, Juergen F. Kolb, Richard Nuccitelli, Christopher J. Osgood, Andrei G. Pakhomov, Michael W. Stacey, James R. Swanson, Jody A. White, Shu Xiao, Jue Zhang, Stephen J. Beebe, Peter F. Blackmore, E. Stephen Buescher

Bioelectrics Publications

Electrical models for biological cells predict that reducing the duration of applied electrical pulses to values below the charging time of the outer cell membrane (which is on the order of 100 ns for mammalian cells) causes a strong increase in the probability of electric field interactions with intracellular structures due to displacement currents. For electric field amplitudes exceeding MV/m, such pulses are also expected to allow access to the cell interior through conduction currents flowing through the permeabilized plasma membrane. In both cases, limiting the duration of the electrical pulses to nanoseconds ensures only nonthermal interactions of the electric …

Using Pareto Fronts To Evaluate Polyp Detection Algorithms For Ct Colonography, Adam Huang, Jiang Li, Ronald M. Summers, Nicholas Petrick, Amy K. Hara

Electrical & Computer Engineering Faculty Publications

We evaluate and improve an existing curvature-based region growing algorithm for colonic polyp detection for our CT colonography (CTC) computer-aided detection (CAD) system by using Pareto fronts. The performance of a polyp detection algorithm involves two conflicting objectives, minimizing both false negative (FN) and false positive (FP) detection rates. This problem does not produce a single optimal solution but a set of solutions known as a Pareto front. Any solution in a Pareto front can only outperform other solutions in one of the two competing objectives. Using evolutionary algorithms to find the Pareto fronts for multi-objective optimization problems has been …

Validating Pareto Optimal Operation Parameters Of Polyp Detection Algorithms For Ct Colonography, Jiang Li, Adam Huang, Nicholas Petrick, Jianhua Yao, Ronald M. Summers, Maryellen L. Giger (Ed.), Nico Karssemeijer (Ed.)

Electrical & Computer Engineering Faculty Publications

We evaluated a Pareto front-based multi-objective evolutionary algorithm for optimizing our CT colonography (CTC) computer-aided detection (CAD) system. The system identifies colonic polyps based on curvature and volumetric based features, where a set of thresholds for these features was optimized by the evolutionary algorithm. We utilized a two-fold cross-validation (CV) method to test if the optimized thresholds can be generalized to new data sets. We performed the CV method on 133 patients; each patient had a prone and a supine scan. There were 103 colonoscopically confirmed polyps resulting in 188 positive detections in CTC reading from either the prone or …

Development Of Fast, Distributed Computational Schemes For Full Body Bio-Models And Their Application To Novel Action Potential Block In Nerves Using Ultra-Short, High Intensity Electric Pulses, Ashutosh Mishra

Electrical & Computer Engineering Theses & Dissertations

An extremely robust and novel scheme for computing three-dimensional, time-dependent potential distributions in full body bio-models is proposed, which, to the best of our knowledge, is the first of its kind. This simulation scheme has been developed to employ distributed computation resources, to achieve a parallelized numerical implementation for enhanced speed and memory capability. The other features of the numerical bio-model included in this dissertation research, are the ability to incorporate multiple electrodes of varying shapes and arbitrary locations. The parallel numerical tool also allows for user defined, current or potential stimuli as the excitation input. Using the available computation …

The Effects Of Ultrashort Pulsed Electric Fields On The Fluorescent Molecule Bodipy Fl C5 Ceramide, Rachael Sara Shevin

Electrical & Computer Engineering Theses & Dissertations

Nanosecond pulsed electric fields are able to manipulate internal cell organelles by taking advantage of the small but finite time required for charge to establish across a capacitive barrier. Pulsed electric fields also affect macromolecular structures such as enzymes and proteins. Application of a single nanosecond pulsed electric field decreases the fluorescence of a commercially available biological dye Bodipy FL C₅ Ceramide, used to observe the Golgi apparatus of living cells. The effect is seen when the fluorophore is exposed to an electric field both in vitro and when incorporated into the Golgi of a living Jurkat cell. Observation …

Temporal Calcium Response Of Jurkat Cells To Nanosecond Pulsed Electric Fields, Shaka Shakar Scarlett

Electrical & Computer Engineering Theses & Dissertations

Nanosecond pulsed electric fields (nsPEF) of megavolt per meter field strengths can interact with subcellular structures [1] and consequently trigger a variety of biological events. The exposure can induce apoptosis, as well as an array of differential "sub-lethal effects." One of the most sensitive and immediate responses is the increase in intracellular calcium concentration in pulsed cells [2], [3][4].We investigated the response of Jurkat cells (a human leukemic cell line) to nsPEFs of 60 ns duration and field strengths from 25 tol00 kV/cm. The development of the induced calcium response in individual cells was studied by spinning-disc confocal microscopy with …

Nanoelectropulse-Driven Membrane Perturbation And Small Molecule Permeabilization, P. Thomas Vernier, Yinghua Sun, Martin A. Gundersen

Bioelectrics Publications

Background
Nanosecond, megavolt-per-meter pulsed electric fields scramble membrane phospholipids, release intracellular calcium, and induce apoptosis. Flow cytometric and fluorescence microscopy evidence has associated phospholipid rearrangement directly with nanoelectropulse exposure and supports the hypothesis that the potential that develops across the lipid bilayer during an electric pulse drives phosphatidylserine (PS) externalization.

Results
In this work we extend observations of cells exposed to electric pulses with 30 ns and 7 ns durations to still narrower pulse widths, and we find that even 3 ns pulses are sufficient to produce responses similar to those reported previously. We show here that in contrast to …

Plasma Membrane Voltage Changes During Nanosecond Pulsed Electric Field Exposure, W. Frey, R. O. Price, P. F. Blackmore, R. P. Joshi, R. Nuccitelli, S. J. Beebe, K. H. Schoenbach, J. F. Kolb

Bioelectrics Publications

The change in the membrane potential of Jurkat cells in response to nanosecond pulsed electric fields was studied for pulses with a duration of 60 ns and maximum field strengths of similar to 100 kV/cm (100 V/cell diameter). Membranes of Jurkat cells were stained with a fast voltage-sensitive dye, ANNINE-6, which has a subnanosecond voltage response time. A temporal resolution of 5 ns was achieved by the excitation of this dye with a tunable laser pulse. The laser pulse was synchronized with the applied electric field to record images at times before, during, and after exposure. When exposing the Jurkat …

Wavelet Analysis In Virtual Colonoscopy, Sharon Greenblum, Jiang Li, Adam Huang, Ronald M. Summers, Armando Manduca (Ed.), Amir A. Amini (Ed.)

Electrical & Computer Engineering Faculty Publications

The computed tomographic colonography (CTC) computer aided detection (CAD) program is a new method in development to detect colon polyps in virtual colonoscopy. While high sensitivity is consistently achieved, additional features are desired to increase specificity. In this paper, a wavelet analysis was applied to CTCCAD outputs in an attempt to filter out false positive detections. 52 CTCCAD detection images were obtained using a screen capture application. 26 of these images were real polyps, confirmed by optical colonoscopy and 26 were false positive detections. A discrete wavelet transform of each image was computed with the MATLAB wavelet toolbox using the …

Simulations Of Transient Membrane Behavior In Cells Subjected To A High-Intensity Ultrashort Electric Pulse, Q. Hu, S. Viswanadham, R. P. Joshi, Karl H. Schoenbach, Stephen J. Beebe, P. F. Blackmore

Bioelectrics Publications

A molecular dynamics (MD) scheme is combined with a distributed circuit model for a self-consistent analysis of the transient membrane response for cells subjected to an ultrashort (nanosecond) high-intensity (approximately 0.01-V/nm spatially averaged field) voltage pulse. The dynamical, stochastic, many-body aspects are treated at the molecular level by resorting to a course-grained representation of the membrane lipid molecules. Coupling the Smoluchowski equation to the distributed electrical model for current flow provides the time-dependent transmembrane fields for the MD simulations. A good match between the simulation results and available experimental data is obtained. Predictions include pore formation times of about 5-6 …

Bioengineering Instructional Framework For Technology Education, Philip A. Reed, Technology Education Department, Old Dominion University, Virginia Bioengineering Writing Team

STEMPS Faculty Publications

No abstract provided.

Room-Temperature Atmospheric Pressure Plasma For Biomedical Applications, Mounir Laroussi, Xinpei Lu

Electrical & Computer Engineering Faculty Publications

As low-temperature non-equilibrium plasmas come to play an increasing role in biomedical applications, reliable and user-friendly sources need to be developed. These plasma sources have to meet stringent requirements such as low temperature (at or near room temperature), no risk of arcing, operation at atmospheric pressure, preferably hand-held operation, low concentration of ozone generation, etc. In this letter, we present a device that meets exactly such requirements. This device is capable of generating a cold plasma plume several centimeters in length. It exhibits low power requirements as shown by its current-voltage characteristics. Using helium as a carrier gas, very little …

Distal Placement Of An End-To-Side Bypass Graft Anastomosis A 3-D Computational Study, John Robert Di Cicco

Mechanical & Aerospace Engineering Theses & Dissertations

A three-dimensional computational fluid dynamics study of blood flow through stenotic arteries has been conducted. Flow phenomena, such as separation regions and turbulence, can be found distal to an arterial stenosis. Frequently, a bypass graft using an end-to-side technique is attached to a stenotic artery to restore adequate blood flow. However, a significant percentage of these grafts fail after thirty postoperative days due to intimal hyperplasia development around the distal anastomosis. Moreover, aberrant wall shear rates have been implicated as a factor in the development of intimal hyperplasia. Thus, the present study examines whether placement of the distal end of …

Field Effect Control Of Electrokinetic Transport Phenomena In Nanofluidics, Song Xue

Mechanical & Aerospace Engineering Theses & Dissertations

Naturally nanofluidics has applications demanding the samples to be handled in exceedingly small quantities due to the small size of the fluidic channels in nanofluidic devices, such as characterization of single biomolecules. Fluids confined in channels of nanometer characteristic dimensions exhibit physical behaviors not observed in large conduits. Charge properties of the nanochannel wall in contact with an aqueous solution play essential roles in the involved electrokinetic transport phenomena occurring in nanofluidic devices. In addition to tuning the charge properties of the nanofluidic channel wall by adjusting the solution properties such as pH and background salt concentration, field effect transistor …

Energy-Landscape-Model Analysis For Irreversibility And Its Pulse-Width Dependence In Cells Subjected To A High-Intensity Ultrashort Electric Pulse, R. P. Joshi, Q. Hu, Karl H. Schoenbach, Stephen J. Beebe

Bioelectrics Publications

We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture …

Astronaut Eva Exposure Estimates From Cad Model Spacesuit Geometry, Giovanni De Angelis, Brooke M. Anderson, William Atwell, John E. Nealy, Gary D. Qualls, John W. Wilson

Mathematics & Statistics Faculty Publications

Ongoing assembly and maintenance activities at the International Space Station (ISS) require much more extravehicular activity (EVA) than did the earlier U.S. Space Shuttle missions. It is thus desirable to determine and analyze, and possibly foresee, as accurately as possible what radiation exposures crew members involved in EVAs will experience in order to minimize risks and to establish exposure limits that must not to be exceeded. A detailed CAD model of the U.S. Space Shuttle EVA Spacesuit, developed at NASA Langley Research Center (LaRC), is used to represent the directional shielding of an astronaut; it has detailed helmet and backpack …

Stimulation Of Capacitative Calcium Entry In Hl-60 Cells By Nanosecond Pulsed Electric Fields, Jody A. White, Peter F. Blackmore, Karl H. Schoenbach, Stephen J. Beebe

Bioelectrics Publications

Nanosecond pulsed electric fields (nsPEFs) are hypothesized to affect intracellular structures in living cells providing a new means to modulate cell signal transduction mechanisms. The effects of nsPEFs on the release of internal calcium and activation of calcium influx in HL-60 cells were investigated by using real time fluorescent microscopy with Fluo-3 and fluorometry with Fura-2. nsPEFs induced an increase in intracellular calcium levels that was seen in all cells. With pulses of 60 ns duration and electric fields between 4 and 15 kV/cm, intracellular calcium increased 200-700 nM, respectively, above basal levels (similar to100 nM), while the uptake of …

Brownian Dynamics Simulation Studies Of Ion Throughput During Cellular Electroporation, Juan A. Gonzalez-Cuevas

Electrical & Computer Engineering Theses & Dissertations

The purpose of the present research work is to analyze the flow of ions through pores formed in the plasma membrane of biological cells during electroporation. In this regard, simulations have been conducted to track the movement of ions in 3-D space based on a Brownian dynamics model, which is mostly deterministic but has some stochastic properties to account for ionic scattering. From the Brownian dynamics simulations, it has been possible to estimate the pore's conductance as well as transport parameters such as the diffusion coefficient and mobility within the pore region, of which there is no experimental data currently …

Time Domain Dielectric Spectroscopy Analysis Of Hl-60 Cell Suspensions After Microsecond And Submicrosecond Pulsed Electric Fields, Allen Laurence Garner

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields (PEF's) above a certain voltage threshold cause electroporation for microsecond pulses and intracellular effects for submicrosecond pulses. Models describing these effects often depend on the electrical properties of the cell, which are altered by the PEF. Time domain dielectric spectroscopy was used to provide data for these models and to measure changes in the conductivity of HL-60 cell suspensions due to single 50 μs and 10 ns PEF's of the same energy. For 1.1 kV/cm, 50 μs pulses, the conductivity rose within a minute after the pulse and dropped dramatically approximately forty minutes after the pulse. For …