Biomedical Engineering and Bioengineering Commons^™

Identification Of Neurobiological Mechanisms Associated With Attention Deficits In Adults Post Traumatic Brain Injury, Ziyan Wu

Dissertations

Traumatic Brain Injury (TBI) is one of the major public health concerns with approximately 70 million new cases occurring worldwide per year. It is often caused by a forceful bump, blow, or jolt to the head, resulting in brain tissue damage and normal brain functions disruption. All grades of TBI, ranging from mild to severe, can cause wide-ranging and long-term effects on affected individuals, resulting in physical impairments, and neurocognitive consequences that permanently affect their abilities to perform daily activities. Attention deficits are the most common persisting neurocognitive consequences following TBI, which significantly contribute to poor academic and social functioning, …

Neurobiological Markers For Remission And Persistence Of Childhood Attention-Deficit/Hyperactivity Disorder, Yuyang Luo

Dissertations

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in children. Symptoms of childhood ADHD persist into adulthood in around 65% of patients, which elevates the risk for a number of adverse outcomes, resulting in substantial individual and societal burden. A neurodevelopmental double dissociation model is proposed based on existing studies in which the early onset of childhood ADHD is suggested to associate with dysfunctional subcortical structures that remain static throughout the lifetime; while diminution of symptoms over development could link to optimal development of prefrontal cortex. Current existing studies only assess basic measures including regional brain activation …

Model-Based Deep Siamese Autoencoder For Clustering Single Cell Rna-Seq Data, Zixia Meng

Theses

In the biological field, the smallest unit of organisms in most biological systems is the single cell, and the classification of cells is an everlasting problem. A central task for analysis of single-cell RNA-seq data is to identify and characterize novel cell types. Currently, there are several classical methods, such as K-means algorithm, spectral clustering, and Gaussian Mixture Models (GMMs), which are widely used to cluster the cells. Furthermore, typical dimensional reduction methods such as PCA, t-SNE, and ZIDA have been introduced to overcome “the curse of dimensionality”. A more recent method scDeepCluster has demonstrated improved and promising performances in …

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Cerebro-Vascular Disruption Mediated Initiation And Propagation Of Traumatic Brain Injury In A Fluid Percussion Injury Model, Xiaotang Ma

Dissertations

Traumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US. There is no FDA-approved drug for the treatment because the injury mechanisms have not been clearly identified. The knowledge gap is addressed here by the lateral fluid percussion injury (FPI) rat model, through the understanding of layer-structured mechanisms from physical vascular rupture to acute necrosis, as well as biochemical changes in perivascular space as secondary events.

Firstly, the cerebrovascular hemorrhage and related infarct volume are investigated as the primary events in moderate FPI, which is found to be increased with injury severity in …

Micro Pipes – A Portable Integrated Platform For Electrochemical Sensing Using Essence Architecture, Hansin Kim

Theses

The field of microfluidics and lab-on-chip (LOC) technology has the potential to have a truly transformative effect in biological engineering. This includes areas such as single-cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Yet despite being the subject of intense research over the past two decades, LOC devices have not been widely adopted. It is increasingly evident that there is a need for an effective and adaptable integration strategy to realize the potential of this technology.

Presented in this thesis is a design for a chip-to-world interface that aims to improve integration while maintaining cost-efficiency and ease of fabrication. …

Lithium As A Possible Therapeutic Drug In Posttraumatic Brain Injury, Tulika Das

Theses

Lithium, a popular drug for treating mental health disorder has shown promising effect in recent research on traumatic brain injury (TBI). The mechanism of lithium for treating bipolar mood disorder is still not properly understood, but recent studies showed that lithium is neuroprotective in TBI. In my thesis, the neuroprotective effects of lithium were examined in primary neuronal culture and mild blunt injury using rodent model of Lateral Fluid Percussion Injury (LFPI). At first determination of the neuroprotective/toxicity effects of lithium in neuronal culture was done and observed that 0.5 - 1.0 mM concentrations were found to be neuroprotective as …

Developmental And Sex Modulated Neurological Alterations In Autism Spectrum Disorder, Azeezat Azeez

Dissertations

Autism Spectrum Disorder (ASD) was first described in 1943 by Dr. Leo Kranner in a case study published in The Nervous Child. It is a neurodevelopment disorder, with a range of clinical symptoms. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), used by clinicians to diagnose mental disorders, a child needs to have persistent social deficits, language impairments, and repetitive behaviors, that cannot be explained by neurological damage or intellectual disability. It is known that children diagnosed with ASD are often are developmentally delayed therefore alterations in the typical developmental trajectory should be a major factor in …

Modulation Of Corticospinal Excitability Induced By Paired Associative Stimulation Combined With Movement, Ahmad O. Alokaily

Dissertations

An essential feature of the brain is its capacity to undergo long-lasting morphological or functional changes in response to experiences or trauma. Advances in noninvasive brain stimulation techniques have led to increased interest in understanding neural mechanisms of neuroplasticity at the network level. Paired associative stimulation (PAS) is one of the most commonly used applications for noninvasive brain stimulation because of its clinical potential as an adjuvant rehabilitative intervention. However, the optimal method for incorporating PAS into rehabilitative activities remains unknown. This dissertation explores different approaches to combining PAS with movement and investigates the enhancement of the specificity of conventional …

Modelling In Vitro Dissolution And Release Of Sumatriptan Succinate From Polyvinylpyrrolidone-Based Microneedles Aided By Iontophoresis, James Paul Ronnander

Dissertations

A novel dissolving microneedle array system is developed to investigate permeation of a sumatriptan succinate formulations through the skin aided by iontophoresis. Three formulations consisting of hydrophilic, positively charged drug molecules encapsulated in a water-soluble biologically suitable polymer, polyvinylpyrrolidone (PVP), have been accepted by the U.S. Food and Drug Administration (FDA). The microneedle systems are fabricated with 600 pyramid-shaped needles, each 500 µm tall, on a 0.785-cm² circular array. In vitro transdermal studies with minipig skin and vertical Franz diffusion cells show > 68% permeation of sumatriptan over a 24-hour period. A combination of microneedle and electrical current density ranging …

A Multimodal Approach To Investigate Brain Reorganization After Spinal Cord Injury Using Functional Magnetic Resonance Imaging And Functional Near-Infrared Spectroscopy, Keerthana Deepti Karunakaran

Dissertations

Traumatic Spinal Cord Injury (SCI) results in structural and functional neurological changes at both the brain and the level of the spinal cord. Anatomical studies indicate decreased grey matter volume in sensorimotor and non-sensorimotor regions of the cortex following SCI; whereas, neurophysiological findings mostly report altered functional activity in the sensorimotor nodes of the cortex, subcortex, and cerebellum. Therefore, it is currently unknown whether tissue atrophy observed in non-motor related areas has any concomitant functional consequences. Furthermore, the neural underpinnings of adaptive neuroplasticity after SCI is not well-defined in the current literature. Hence, this dissertation is a pioneer study investigating …

Dual Modality Optical Coherence Tomography : Technology Development And Biomedical Applications, Farzana Rahmat Zaki

Dissertations

Optical coherence tomography (OCT) is a cross-sectional imaging modality that is widely used in clinical ophthalmology and interventional cardiology. It is highly promising for in situ characterization of tumor tissues. OCT has high spatial resolution and high imaging speed to assist clinical decision making in real-time.

OCT can be used in both structural imaging and mechanical characterization. Malignant tumor tissue alters morphology. Additionally, structural OCT imaging has limited tissue differentiation capability because of the complex and noisy nature of the OCT signal. Moreover, the contrast of structural OCT signal derived from tissue’s light scattering properties has little chemical specificity. Hence, …

Interventions Of Waterjet Technology In Skin Incisions, Nadi Atalla

Dissertations

This research explores the use of waterjet (WJ) technology in performing skin incisions. The study defines the analytical relationships between the skin properties and the operating parameters of the WJ which include the skin thickness, its elastic modulus, the WJ pressure, the nozzle’s orifice diameter, its stand-off distance and the traverse speed of the WJ as well as the duration of applying the WJ pressure. An analytical model is developed to measure the depth incision of the skin, the water pressure and the water velocity, while using a WJ. Systemization and optimization models that determine the optimal operating parameters levels …

Vergence Eye Movement Parameters For Pre/Post-Obvat And Sham Therapy On Binocularly Normal Controls, Joel V. Rajah

Theses

Vergence is the disjunctive movement of the eyes to maintain single binocular vision. Vergence eye movements are necessary to maintain the object of interest on the fovea of each eye as an individual looks from one object to another. Recent studies show that office based vergence/accommodative therapy (OBVAT) is an effective treatment for the binocular dysfunction known as convergence insufficiency. This study was performed to investigate the changes in oculomotor parameters parameter data for pre- and post-therapy subjects who are binocularly normal controls. A haploscope was used to collect eye movement data pre- and post-therapy. The analysis of the eye …

Longitudinal Investigation Of Disparity Vergence In Young Adult Convergence Insufficiency Patients, Patrick C. Crincoli

Theses

Vergence is a form of eye movement in which the eyes move in opposite directions to minimize retinal disparity. It allows an object at different distances from a viewer to appear single during binocular vision by centering the image on the fovea of each retina. Convergence insufficiency (CI) is a binocular disfunction in which blurry and double vision is a symptom. Office-based Vergence/Accommodative Therapy (OBVAT) has been shown to be effective in treating CI. A randomized clinical trial was designed to study fifty participants with CI before and after therapy using randomized therapy treatment (active and placebo), standardized clinical definitions, …

Experimentally Linking Head Kinematics To Brain Deformation, Imouline Algharbi

Theses

Traumatic brain injury (TBI) research is used to study the effects of brain injuries and the rehabilitations for them. TBI contributes to major cause of disability and deaths quantifying up to 30% of all the head injuries. To mimic real world impact to understand the mechanism of injury head-surrogate models are used. This thesis describes a method to record head kinematics from acceleration and angular rate sensors of head-brain surrogate model for blast and blunt injury. This methodology is validated through experimental testing. To get a better insight of the head kinematics experienced by a real skull a drop tower …

Cardiac Regenerative Medicine: Insights From Healthy And Diseased Engineered Tissues, Pamela Grace Hitscherich

Dissertations

Cardiovascular disease remains the leading cause of mortality in the United States. Current tissue engineering approaches have fallen short of promoting fully functional cardiovascular cells and the post-myocardial infarction microenvironment is still not well understood. These gaps in knowledge are addressed in this dissertation through the development of in vitro engineered cardiac tissues using electroactive materials to enhance the differentiation of pluripotent stem cell derived cardiomyocytes and through the development of in vitro myocardial inflammation models dedicated to understanding cardiomyocytes and macrophages interactions.

Specifically, piezoelectric poly (vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) supports the attachment and survival of mouse embryonic stem cell derived …

Temporal And Spatial Effects Of Shock Overpressure On Blood-Brain Barrier Permeability In Blast-Induced Traumatic Brain Injury, Matthew Joseph Kuriakose

Dissertations

Exposure to shock waves is the leading cause of traumatic brain injury (TBI) in military personnel and blast-induced TBI (bTBI) is considered the signature wound in recent conflicts in Iraq and Afghanistan. Many researchers attempt to replicate field-relevant shock waves in laboratory settings through the use of gas-driven shock tubes in order to investigate the generation and propagation of shock waves and also explore possible mechanisms of bTBI. Among several injury mechanisms of bTBI, damage to the blood-brain barrier (BBB) has been identified as a potential candidate and has been the focus of several clinical and experimental investigations aimed to …

Prediction Of Forelimb Muscle Activities And Movement Phases Using Corticospinal Signals In The Rat, Sinan Gok

Dissertations

The targeted population for this project is primarily patients with high level spinal cord injury (SCI) and individuals with motor neuron diseases (MND). In both SCI and MND cases motor control is interrupted due to lack of communication between the brain and the musculature, although both sides are otherwise functional. The approach in this project is to use neural engineering techniques to restore the motor function that was lost because of an injury or disease.

Brain-computer interfaces (BCIs) attempt to extract the volitional signals from the cortex when the brain's normal outputs to the musculoskeletal system are impaired. However, BCIs …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Fluorescent Probes And Functionalized Nanoparticles For Bioimaging: Synthesis, Photophysical Properties And Applications, Xinglei Liu

Dissertations

The development of new organic molecular probes with excellent photophysical properties and high fluorescence quantum yields is of considerable interest to many research areas including one- and two-photon fluorescence microscopy, fluorescence-based sensing methodologies, and cancer therapy. Series of organic linear-/non-linear optical molecules including squaraine derivatives, and fluorene derivatives as well as other bioconjugates are designed and synthesized during the doctoral study for the aim of ion detection (Chapter 5), photo dynamic therapy, and deep-tissue imaging (Chapter 4). These optical probes are capable of absorbing light in the near infrared (NIR) window and thus have deeper penetration and cause less photodamage …

Head Impacts In The A7fl, Stephen Mcgeever

Theses

The American 7s Football League (A7FL) is a semi professional football league that does not use helmets or pads. The theory is that the game is safer without helmets and pads because players feel more vulnerable and use a different tackling technique to protect themselves. Rather than lowering and leading with their head when the players tackle, as many helmeted football players do, A7FL players primarily use their arms to wrap the opponent up. A7FL players were given Vector mouth guards designed by Athlete Intelligence to wear. These mouth guards have built in tri-axial accelerometers to record impact data, which …

Changes In Nadph Oxidase (Nox) Protein Isoforms And Downstream Reactions As Function Of Time And Overpressure In Blast Tbi, Smit Prakash Shah

Theses

Blast-induced Traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and training sites with long-term neurological and psychological pathologies. Among many pathological sequela of blast TBI, oxidative stress has been identified as a major factor contributing to the pathophysiology of bTBI. Recent studies have demonstrated activation of oxidative stress pathways following blast injury but their distribution among different brain regions as function of post injury time and Blast over pressure (BOP) have not been explored. The present study examines the protein expression of NADP oxidase (NOX) isoforms 1 & 2, corresponding superoxide production, a …

Carbon Fiber Electrodes For In Vivo Neural Recording, Esma Cetinkaya

Theses

Multi-channel micro electrodes for neural recording is a growing field that thrives on novel materials and fabrication techniques offered by micro fabrication technology. The material and the design of microelectrodes have a critical role on the quality of neural signals recorded. The neural signals collected by chronic implantation of these devices in experimental animals reveal new information about the brain functions and guide the development of new diagnostic and treatment options for neurological disorders.

Ideally, a microelectrode should meet two important criteria: longevity after implantation and minimal tissue insult. Carbon fibers` high tensile strength and flexibility allow fabrication of micro-scale …

Modeling Subconcussive And Cumulative Subconcussive Impacts Using A Lateral Fluid Percusion Injury Device, Todd Long

Dissertations

Repetitive mTBI and concussion are a major risk factor for developing long-term cognitive and behavioral impairments. Curiously, cumulative head injuries sustained over an individuals’ career, involving contact activities (e.g. athletes and military personnel), are beginning to be implicated in long-term consequences, such as dementia. Recently, chronic traumatic encephalopathy (CTE) has gained momentum in the science and medical community as a neurodegenerative disease of repetitive head injuries. CTE was observed at autopsy of former athletes that did not closely correlate with a clinical history of concussion. Thus, suggesting cumulative subconcussive insults may induce long-term damage.

Investigating the etiology of subconcussive and …

Subject And Group Level Changes And Comparison In Functional Connectivity Under Low Vs. High Cognitively Demanding Naturalistic Viewing Conditions Using Fmri, Rakibul Hafiz

Theses

Resting State fMRI is used extensively for analysing brain regions. fMRI is also used to determine task induced activations from cerebral networks. This study involves both rest and task activation data and implements statistical methods applied on Blood Oxygenation Level Dependent (BOLD) signals. The conventional task based designs are very specific and may not reflect day to day activities. The two task conditions in this study are watching a movie called INSCAPE with low cognitive load and segments of contextual Hollywood movies under continuous and natural conditions.

The aim is to investigate individual and group level Functional Connectivity changes between …

Spatial And Temporal Deformation Pattern Of The Brain From Blunt Trauma, Abdus Ali

Theses

It is widely accepted that under extreme loadings the soft tissue of the brain will deform inside the skull, creating large amounts of both stress and strain on the tissue. This can result in a focal injury, or in the case of acceleration and deceleration, diffuse injuries. Any attempt at understanding the underlying mechanisms and effects of TBI, have to start by focusing on what is actually occurring within the brain. The objective of this experiment is to record differences in the spatial and temporal patterns of deformation within the brain during blunt trauma when changing impact parameters. A linear …

Interaction Of Voluntary Activity And Functional Electrical Stimulation In The Upper Extremity As A Method For Short-Term Alteration Of Corticospinal Excitability And Force Control, Katherine Maia Gerton

Theses

Repetitive movement training (RMT) is a well-established method for rehabilitating functional movement. However, many stroke survivors are not able to participate in RMT for the necessary duration to produce results due to rapid muscle fatigue or inability to perform the desired movement at all. Often, functional electrical stimulation (FES) is applied passively, as a rehabilitative therapy, to stroke subjects who are unable to participate in RMT. The effects of voluntary contraction and FES are not well understood for the upper extremity following a stroke. This experiment was designed to elucidate the mechanisms of functional and neurophysiological changes associated with combining …

The Use Of Audio Stimulation To Affect Sensorimotor Learning, Gregory Nicholas Ranky

Dissertations

Sensorimotor learning for the hand and fingers can be conducted using both hardware and software components, but the training regime is also important. Using repetitive sequence tapping allows measurement of defined metrics in a controlled, safe environment, and therefore statistical indications for subject improvement.

The process of entrainment, when a subject’s own movements synchronize to an external signal, has been tested in prior studies for memorization and recognition, but has not been investigated for correlation with sensorimotor learning.

This is tested with selected custom isochronic audio tones, combined with sequential finger tapping on a standard computer keyboard.

Whilst there were …

A Novel Approach To Increase Upper Extremity Active Range Of Motion For Individuals With Duchenne Muscular Dystrophy Using Admittance Control, Madeline Catherine Corrigan

Dissertations

Duchenne muscular dystrophy (DMD), a neuromuscular disease with a prevalence of 1 in 3,500-5,000 male births, results in progressive muscle weakness causing loss of independence and imposing the demands of costly and intrusive assistive support and personal care for daily living tasks. Upper extremity function begins to decline while ambulation is still possible and gradually progresses with time, playing a prominent role in loss of independence. Importantly, upper extremity functional limitations exist despite residual muscle strength that is insufficient to lift the arms against gravity. Presently, there exist a number of commercially available assistive devices aimed at augmenting upper extremity …