Biomedical Engineering and Bioengineering Commons^™

Independent Component Analysis Enhancements For Source Separation In Immersive Audio Environments, Yue Zhao

Theses and Dissertations--Electrical and Computer Engineering

In immersive audio environments with distributed microphones, Independent Component Analysis (ICA) can be applied to uncover signals from a mixture of other signals and noise, such as in a cocktail party recording. ICA algorithms have been developed for instantaneous source mixtures and convolutional source mixtures. While ICA for instantaneous mixtures works when no delays exist between the signals in each mixture, distributed microphone recordings typically result various delays of the signals over the recorded channels. The convolutive ICA algorithm should account for delays; however, it requires many parameters to be set and often has stability issues. This thesis introduces the …

Development Of An Eeg Brain-Machine Interface To Aid In Recovery Of Motor Function After Neurological Injury, Elizabeth Salmon

Theses and Dissertations--Biomedical Engineering

Impaired motor function following neurological injury may be overcome through therapies that induce neuroplastic changes in the brain. Therapeutic methods include repetitive exercises that promote use-dependent plasticity (UDP), the benefit of which may be increased by first administering peripheral nerve stimulation (PNS) to activate afferent fibers, resulting in increased cortical excitability. We speculate that PNS delivered only in response to attempted movement would induce timing-dependent plasticity (TDP), a mechanism essential to normal motor learning. Here we develop a brain-machine interface (BMI) to detect movement intent and effort in healthy volunteers (n=5) from their electroencephalogram (EEG). This could be used in …

Noninvasive Near-Infrared Diffuse Optical Monitoring Of Cerebral Hemodynamics And Autoregulation, Ran Cheng

Theses and Dissertations--Biomedical Engineering

Many cerebral diseases are associated with abnormal cerebral hemodynamics and impaired cerebral autoregulation (CA). CA is a mechanism to maintain cerebral blood flow (CBF) stable when mean arterial pressure (MAP) fluctuates. Evaluating these abnormalities requires direct measurements of cerebral hemodynamics and MAP. Several near-infrared diffuse optical instruments have been developed in our laboratory for hemodynamic measurements including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), hybrid NIRS/DCS, and dual-wavelength DCS flow-oximeter. We utilized these noninvasive technologies to quantify CBF and cerebral oxygenation in different populations under different physiological conditions/manipulations. A commercial finger plethysmograph was used to continuously monitor MAP. For investigating …

Effects Of Acute Stretch On Cardiac Electrical Properties In Swine, Anuj Agarwal

Theses and Dissertations--Biomedical Engineering

Stretch is known to result in an electrically less stable ventricular substrate, yet the reported effects of stretch on measured electrophysiological parameters have been inconsistent and even contradictory. The goal of this study was to evaluate the effects of acute mechanical stretch on cardiac electrical features thought to be key in generation of arrhythmia, namely restitution of action potential duration (APD), electrical memory, and onset of alternans.

Microelectrodes were used to record intracellular potentials pre, during, and post-stretch from isolated right ventricular tissues from swine. In separate experiments, the effects of two levels of stretch were quantified. Pacing protocols employing …

Hysteresis In Repolarization Of Cardiac Action Potentials: Effects Of Spatial Heterogeneity And Slow Repolarization Currents, Linyuan Jing

Theses and Dissertations--Biomedical Engineering

Repolarization alternans, i.e. beat-to-beat variation of repolarization of action potential, is proposed as a predictor of life-threatening arrhythmias. Restitution relates repolarization duration with its previous relaxation time, i.e. diatstolic interval (DI), and is considered a dominant mechanism for alternans. Previously, we observed that different repolarization durations at the same DI during decelerating and accelerating pacing, i.e. restitution displays hysteresis, which is a measure of “cardiac memory”.

Objective of the current study was to investigate in the pig 1) the mechanism for a previously observed hysteresis type phenomenon, where alternans, once started at higher heart rate, persists even when heart rate …

Development Of A Multilayered Association Polymer System For Sequential Drug Delivery, Sharath Kumar Chinnakavanam Sundararaj

Theses and Dissertations--Biomedical Engineering

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone …

Growth Plate Regeneration Using Polymer-Based Scaffolds Releasing Growth Factor, Amanda Clark

Theses and Dissertations--Biomedical Engineering

Currently growth plate fractures account for nearly 18.5% of fractures in children and can lead to stunted bone growth or angular deformation. If the body is unable to heal itself a bony bar forms, preventing normal bone growth. Clinical treatment involves removing the bony bar and replacing it with a filler substance, which causes poor results 60% of the time.

Using primarily poly(lactic-co-glycolic acid) (PLGA) as the scaffold material, the goal was to develop an implant that would support to the implant site, allow for cell ingrowth, and degrade away over time. Porous scaffolds were fabricated from PLGA microspheres using …

Recovering Local Neural Tract Directions And Reconstructing Neural Pathways In High Angular Resolution Diffusion Mri, Ning Cao

Theses and Dissertations--Computer Science

Magnetic resonance imaging (MRI) is an imaging technique to visualize internal structures of the body. Diffusion MRI is an MRI modality that measures overall diffusion effect of molecules in vivo and non-invasively. Diffusion tensor imaging (DTI) is an extended technique of diffusion MRI. The major application of DTI is to measure the location, orientation and anisotropy of fiber tracts in white matter. It enables non-invasive investigation of major neural pathways of human brain, namely tractography. As spatial resolution of MRI is limited, it is possible that there are multiple fiber bundles within the same voxel. However, diffusion tensor model is …

Applications Of Antioxidant And Anti-Inflammatory Polymers To Inhibit Injury And Disease, David B. Cochran

Theses and Dissertations--Chemical and Materials Engineering

There is an undeniable link between oxidative stress, inflammation, and disease. Currently, approaches using antioxidant therapies have been largely unsuccessful due to poor delivery and bioavailability. Responding to these limitations, we have developed classes of polymer and delivery systems that can overcome the challenges of antioxidant and anti-inflammatory therapy. In our initial studies, nanoparticles of poly(trolox), a polymeric form of trolox, were surface-modified with antibodies. This modification allows for specific targeting to endothelial cells, affording controllable and localized protection against oxidative stress. We have shown these targeted nanoparticles bind, internalize, and provide protection against oxidative stress generation and cytotoxicity from …

Load-Relaxation Properties Of The Human Trunk In Response To Prolonged Flexion: Measuring And Modeling The Effect Of Flexion Angle, Nima Toosizadeh, Maury A. Nussbaum, Babak Bazrgari, Michael L. Madigan

Biomedical Engineering Faculty Publications

Experimental studies suggest that prolonged trunk flexion reduces passive support of the spine. To understand alterations of the synergy between active and passive tissues following such loadings, several studies have assessed the time-dependent behavior of passive tissues including those within spinal motion segments and muscles. Yet, there remain limitations regarding load-relaxation of the lumbar spine in response to flexion exposures and the influence of different flexion angles. Ten healthy participants were exposed for 16 min to each of five magnitudes of lumbar flexion specified relative to individual flexion-relaxation angles (i.e., 30, 40, 60, 80, and 100%), during which lumbar flexion …

Noninvasive Optical Characterization Of Muscle Blood Flow, Oxygenation, And Metabolism In Women With Fibromyalgia, Yu Shang, Katelyn Gurley, Brock Symons, Douglas Long, Ratchakrit Srikuea, Leslie J. Crofford, Charlotte A. Peterson, Guoqiang Yu

Biomedical Engineering Faculty Publications

INTRODUCTION: Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.

METHODS: Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily …

Ultrastable Synergistic Tetravalent Rna Nanoparticles For Targeting To Cancers, Farzin Haque, Dan Shu, Yi Shu, Luda S. Shlyakhtenko, Piotr G. Rychahou, B. Mark Evers, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

One of the advantages of nanotechnology is the feasibility to construct therapeutic particles carrying multiple therapeutics with defined structure and stoichiometry. The field of RNA nanotechnology is emerging. However, controlled assembly of stable RNA nanoparticles with multiple functionalities which retain their original role is challenging due to refolding after fusion. Herein, we report the construction of thermodynamically stable X-shaped RNA nanoparticles to carry four therapeutic RNA motifs by self-assembly of reengineered small RNA fragments. We proved that each arm of the four helices in the X-motif can harbor one siRNA, ribozyme, or aptamer without affecting the folding of the central …

Noninvasive Optical Quantification Of Absolute Blood Flow, Blood Oxygenation, And Oxygen Consumption Rate In Exercising Skeletal Muscle, Katelyn Gurley, Yu Shang, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study investigates a method using novel hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] to obtain continuous, noninvasive measurement of absolute blood flow (BF), blood oxygenation, and oxygen consumption rate (V̇O₂) in exercising skeletal muscle. Healthy subjects (n=9) performed a handgrip exercise to increase BF and V̇O₂ in forearm flexor muscles, while a hybrid optical probe on the skin surface directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO₂], [Hb], and THC), tissue oxygen saturation (S_tO₂), relative BF (rBF), and relative oxygen …

Towards Omni-Tomography -- Grand Fusion Of Multiple Modalities For Simultaneous Interior Tomography, Ge Wang, Jie Zhang, Hao Gao, Victor Weir, Hengyong Yu, Wenxiang Cong, Xiaochen Xu, Haiou Shen, James Bennett, Mark Furth, Yue Wang, Michael Vannier

Radiology Faculty Publications

We recently elevated interior tomography from its origin in computed tomography (CT) to a general tomographic principle, and proved its validity for other tomographic modalities including SPECT, MRI, and others. Here we propose "omni-tomography", a novel concept for the grand fusion of multiple tomographic modalities for simultaneous data acquisition in a region of interest (ROI). Omni-tomography can be instrumental when physiological processes under investigation are multi-dimensional, multi-scale, multi-temporal and multi-parametric. Both preclinical and clinical studies now depend on in vivo tomography, often requiring separate evaluations by different imaging modalities. Over the past decade, two approaches have been used for multimodality …

The Influence Of Membrane Cholesterol-Related Shear Stress Mechanosensitivity On Neutrophil Flow Behavior, Xiaoyan Zhang

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a dominant risk factor for a variety of cardiovascular diseases and involves a chronic inflammatory component in which neutrophil activity plays a critical role. Recently, fluid shear stress mechanotransduction has been established as a control mechanism that regulates the activity of neutrophils by reducing the formation of pseudopods and the surface expression of CD18 integrins, thereby rendering these cells rounded, deformable, and non-adhesive. This is critical for maintaining a healthy circulation, because chronically activated neutrophils not only release excess cytotoxic and degradative agents but also exhibit a reduced efficiency to pass through the small vessels of the microcirculation …

Multimodal Imaging Evidence For Axonal And Myelin Deterioration In Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Neuroscience Faculty Publications

White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using …

Validation Of Computational Fluid Dynamic Simulations Of Membrane Artificial Lungs With X-Ray Imaging, Cameron Christopher Jones

Theses and Dissertations--Biomedical Engineering

The functional performance of membrane oxygenators is directly related to the perfusion dynamics of blood flow through the fiber bundle. Non-uniform flow and design characteristics can limit gas exchange efficiency and influence susceptibility of thrombus development in the fiber membrane. Computational fluid dynamics (CFD) is a powerful tool for predicting properties of the flow field based on prescribed geometrical domains and boundary conditions. Validation of numerical results in membrane oxygenators has been predominantly based on experimental pressure measurements with little emphasis placed on confirmation of the velocity fields due to opacity of the fiber membrane and limitations of optical velocimetric …

Use Of Hybrid Diffuse Optical Spectroscopies In Continuous Monitoring Of Blood Flow, Blood Oxygenation, And Oxygen Consumption Rate In Exercising Skeletal Muscle, Katelyn Gurley

Theses and Dissertations--Biomedical Engineering

This study combines noninvasive hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] with occlusive calibration for continuous measurement of absolute blood flow (BF), tissue blood oxygenation (S_tO₂), and oxygen consumption rate (VO₂) in exercising skeletal muscle. Subjects performed rhythmic dynamic handgrip exercise, while an optical probe connected to a hybrid NIRS/DCS flow-oximeter directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO₂], [Hb], and [tHb]), S_tO₂, relative BF (rBF), and relative VO₂ (rVO₂) in the forearm flexor muscles. Absolute baseline BF and …

Bisphosphonates And Bone Microdamage, William A. Caruthers

Theses and Dissertations--Biomedical Engineering

Osteoporosis is a significant healthcare issue due to the increasing elderly population. Bisphosphonates are used to treat osteoporosis by reducing the rate of resorption, increasing bone mineral density (BMD) and thereby reducing fracture risk. Long-term bisphosphonate treatment, however, has been associated with low-energy fractures. Bone microdamage may provide a partial explanation for one of the mechanisms responsible for these fractures since it has been shown to reduce bone toughness, fracture resistance, and bone strength. The goal of this study was to quantify the changes in bone microdamage parameters with the duration of bisphosphonate treatment. This study selected, stained, and histomorphometrically …

Noninvasive Assessment And Modeling Of Diabetic Cardiovascular Autonomic Neuropathy, Siqi Wang

Theses and Dissertations--Biomedical Engineering

Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. …

Ultrasonic Concentration Of Microorganisms, Samuel J. Mullins

Theses and Dissertations--Biosystems and Agricultural Engineering

Concentration of microorganisms from a sample volume would increase the limits of detection of samples used for rapid-detection methods. Rapid detection methods are is advantageous for the food industry to rapidly test for bacteria in order release products on a timely basis. Ultrasonic concentration was considered a promising method for manipulation of microorganisms. An ultrasonic chamber consisting of parallel piezoceramic discs with a reticulated polyurethane foam mesh was used to concentrate Saccharomyces cerevisiae yeast and Escherichia coli bacteria. The concentration of yeast was seen to increase by 200% (from 8.0 x 10⁴ cells mL^-1 to 2.4 x 10 …

Bifunctional Bisphosphonates For Delivering Biomolecules To Bone, Jivan N. Yewle

Theses and Dissertations--Chemistry

Active targeting with controlled delivery of therapeutic agents to bone is an ideal approach for treatment of several bone diseases. Since bisphosphonates (BPs) are known to have high affinity to bone mineral and are being widely used in treatment of osteoporosis, they are well-suited for drug targeting to bone. For this purpose, bifunctional hydrazine-bisphosphonates (HBPs) with spacers of various lengths and lipophilicity were synthesized and studied. Crystal growth inhibition assays demonstrated that the HBPs with shorter spacers bound more strongly to bone mineral, hydroxyapatite (HA), than did alendronate. HBPs were also demonstrated to be non-toxic to MC3T3-E1 pre-osteoblasts. The targeted …

Protein Based Biomimetic Approachs To Surface Hemocompatibility And Biocompatibility Enhancement, Matthew Thomas Dickerson

Theses and Dissertations--Chemical and Materials Engineering

T. pallidum can survive a primary immune response and continue growing in the host for an extended period of time. T. pallidum is thought to bind serum fibronectin (FN) through Tp0483 on the surface to obscure antigens. A Tp0483 fragment (rTp0483) was adsorbed onto functionalized self-assembled monolayers (SAMs) with FN. FN capture by adsorbed rTp0483 depended greatly on surface chemistry with COO- groups being best for FN binding. Hemocompatibility was determined by analysis of plasma protein adsorption, intrinsic pathway activation, and platelet activation. rTp0483+FN bound an equal or lesser amount of fibrinogen (Fg), human serum albumin (HSA), and factor XII …

Correlation Between Alternans Of Early And Late Phases Of Ventricular Action Potential, Sonam Chourasia

Theses and Dissertations--Biomedical Engineering

Several studies suggest that action potential duration (APD) alternans play an important role in initiation of arrhythmias, while less is known about the alternans of early phases of action potential (AP) and phase relation between the two. Transmembrane potentials recorded from swine and canine ventricles were analyzed to determine the correlation and phase relation between alternans of early and late phases of an AP. In both species, for activation intervals ≤ 400 ms, action potential amplitude (APA) alternans occurred≥ 50% of times when APD alternans occurred and vice versa, both were mostly in phase. Also, alternans of APA and APD …

Influence Of Tissue Absorption And Scattering On Diffuse Correlation Spectroscopy Blood Flow Measurements, Daniel Irwin

University of Kentucky Master's Theses

This investigation evaluates the influences of optical property assumptions on nearinfrared diffuse correlation spectroscopy (DCS) flow index measurements. Independent variation is induced in optical properties, absorption coefficient (μ_a) and reduced scattering coefficient (μ_s’), of liquid phantoms with concurrent measurements of flow indices. A hybrid instrument is incorporated consisting of a dual-wavelength (785 and 830 nm) DCS flow device to obtain flow indices and a frequency-domain tissue-oximeter for optical properties. Flow indices are calculated with measured μ_a and μ_s’ or assumed constant μ_a and μ_s’. Inaccurate μ_s’ assumptions produced …

Distal Radioulnar Joint Biomechanics And Forearm Muscle Activity, Joseph Scott Bader

University of Kentucky Doctoral Dissertations

Optimal management of fractures, post-traumatic arthritis and instability of the distal radioulnar joint (DRUJ) requires an understanding of the forces existing across this joint as a function of the activities of daily living. However, such knowledge is currently incomplete. The goal of this research was to quantify the loads that occur at the DRUJ during forearm rotation and to determine the effect that individual muscles have on those loads.

Human and cadaver studies were used to analyze the shear (A-P), transverse (M-L) and resultant forces at the DRUJ and to determine the role that 15 individual muscles had on those …

The Effect Of Practice On Eye Movements In The 1/D Paradigm, Will Seidelman

University of Kentucky Master's Theses

Previous studies have demonstrated that observers may ignore highly salient feature singletons during a conjunction search task through focusing the attentional window (Belopolsky, Zwaan, Theeuwes, & Kramer, 2007), or by the suppression of bottom-up information (Treisman & Sato, 1990). In the current study, observers’ eye movements were monitored while performing a search task in which a feature singleton was present and corresponded with the target at a chance level. With practice, observers were less likely to make an initial saccade toward the singleton item, but initial saccades directed at the target were likely throughout. Results demonstrate that, in an effort …

Development, Validation, And Application Of A Noninvasive Spinal Motion Measurement System, Shaun Kevin Stinton

University of Kentucky Doctoral Dissertations

Spontaneous vertebral fractures are a large and growing health care problem. Biomechanical factors, specifically, abnormal posture or gait‐related spinal motion may interact with age‐weakened bone to induce altered spinal biomechanics that in turn increase the likelihood of vertebral body fracture. This research takes steps towards the goal of reducing the number of vertebral fractures in two phases: 1) Validation of a noninvasive spinal motion measurement system in cadaver torsos and 2) Application of the measurement system in human subjects.

The cadaver study compared vertebral motion at 4 levels (T7,T12,L3,L5) as measured by adhesive skin markers versus motion measured by bone …

Computational Analyses Of The Uptake And Distribution Of Carbon Monoxide (Co) In Human Subjects, Kinnera Chada

University of Kentucky Doctoral Dissertations

Carbon monoxide (CO) is an odorless, colorless, tasteless gas that binds to hemoglobin with high affinity. This property underlies the use of low doses of CO to determine hemoglobin mass (M_Hb) in the fields of clinical and sports medicine. However, hemoglobin bound to CO is unable to transport oxygen and exposure to high CO concentrations is a significant environmental and occupational health concern. These contrasting aspects of CO—clinically useful in low doses but potentially lethal in higher doses—mandates a need for a quantitative understanding of the temporal profiles of the uptake and distribution of CO …

Modeling And Quantitative Analysis Of White Matter Fiber Tracts In Diffusion Tensor Imaging, Xuwei Liang

University of Kentucky Doctoral Dissertations

Diffusion tensor imaging (DTI) is a structural magnetic resonance imaging (MRI) technique to record incoherent motion of water molecules and has been used to detect micro structural white matter alterations in clinical studies to explore certain brain disorders. A variety of DTI based techniques for detecting brain disorders and facilitating clinical group analysis have been developed in the past few years. However, there are two crucial issues that have great impacts on the performance of those algorithms. One is that brain neural pathways appear in complicated 3D structures which are inappropriate and inaccurate to be approximated by simple 2D structures, …