Engineering Commons^™

Ultra-High Field Mri Methods For Precise Anatomical And Spectroscopic Measurements In The Brain And Application To Neurological And Neuropsychiatric Diseases, Judy Alper

Dissertations and Theses

Neurological and neuropsychiatric diseases and disorders are a major burden on society, impairing the health and functioning of millions of people every year. There is a need to define the biological bases of these diseases and identify potential biomarkers to improve diagnosis, monitoring, and treatment efficacy across multiple diseases.

Magnetic resonance imaging (MRI) is a noninvasive imaging technique which facilitates detection of brain lesions and visualization of the brain overall. However, limitations in contrast and resolution at clinical field strengths may hinder investigation of the underlying biological mechanisms of these diseases. Ultra-high field MRI scanners, such as those at 7-Tesla, …

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

Dissertations and Theses

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

Cell Mechanics In Cardiovascular Disease And Electrospun Scaffold For Vascular Tissue Engineering, Alex Park Rickel

Dissertations and Theses

Cardiovascular disease (CVD) is the leading cause of death worldwide. Atherosclerosis, one of the primary CVDs, is characterized as a chronic inflammatory disease. In the initial stages of atherosclerosis, there is a buildup of cholesterol and lipoproteins that triggers monocytes to enter the arterial wall and begin accumulating lipids. Vascular smooth muscle cells (VSMCs) begin to detach and migrate from the media toward the intima in a process known as phenotypic switching. Phenotypic switching transitions VSMCs from a contractile to synthetic phenotype and they gain the capacity for migration, proliferation, and secretion of extracellular matrix (ECM) proteins. Synthetic VSMCs experience …

Modulation Of Brain Tissue Transport And Endothelial Glycocalyx And Tight Junctions Of The Blood-Brain Barrier By Transcranial Direct Current Stimulation, Yifan Xia

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive approach to treat a broad range of brain disorders and to enhance memory and cognition in healthy individuals. In addition to directly acting on neurons by modulating the membrane potential, inducing neuronal polarization and changing cortical excitability in the brain to achieve its therapeutic effects, prior studies found that tDCS can transiently enhance the permeability (P) of the blood-brain barrier (BBB), the interface between blood circulation and brain tissue. Brain extracellular space (ECS) is a narrow microenvironment which surrounds every cell in the central nervous system (CNS). ECS occupies ~20% of brain …

Development Of A Targeted Drug Delivery System For Intracranial Atheroslerotic Disease, Kirby Fuglsby

Dissertations and Theses

Intracranial atherosclerotic disease (ICAD) remains a leading cause of ischemic events such as stroke. However, the use of drug coated balloons (DCBs) containing paclitaxel (PAT) in the brain vasculature remains limited. This is the result of several factors including particulate shed from polymer excipients, PAT toxicity, and poor blood-brain barrier (BBB) permeability of PAT. Therefore, there is a need for novel PAT and excipient formulations for balloon coatings to improve delivery of PAT to the arterial wall in ICAD while reducing off target drug effects and particulate shed. GM1 has previously been shown to cross the BBB and have high …

Analysis Of Eye Movements To Cartoon Faces In Videos, Kaustubh Sapru

Dissertations and Theses

Saccades are rapid eye movements that move our gaze between successive points of fixation. They are indicative of how we direct our attention and therefore play a role in memory and cognition. For static images, it is established that saccades move faster to faces compared to other objects. We hypothesize that the same is true for videos. To test this hypothesis, saccades to faces in motion pictures have been analyzed. The analysis here entails the recording of saccades to two videos followed by a statistical study of saccades going towards faces or going away from faces. What makes this study …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …

Novel Mechanisms Of Dc And Kilohertz Electrical Stimulation, Zeinab Esmaeilpour

Dissertations and Theses

Transcranial electrical stimulation is a promising technique where a weak electrical current is applied to the scalp with the goal of modulating brain activity. Understanding the cellular mechanism of direct current (DC) and kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation. More specifically, there is a large mismatch between enthusiasm for clinical applications of the method and understanding of DC and kHz novel mechanisms of action. This dissertation is centered around two main fundamental aims: 1) systematic study of the acute and long-term effects of kilohertz electrical stimulation and amplitude-modulated waveform with kHz carrier frequency using a well-established …

Impact Of Percutaneous Transluminal Intervention On Vascular Hypoxia And The Role Of Micro-Calcifications On Atherosclerotic Plaque Rupture, Andrea Corti

Dissertations and Theses

Atherosclerotic disease is initiated by cholesterol build-up beneath the endothelium, which evolves into a fibroatheroma, a lipid-rich plaque covered by a fibrous cap. Many of these plaques are considered as vulnerable, as they grow to occlude the luminal section of the artery (chronically stenotic) or become mechanically unstable with a higher chance of rupturing (rupture-prone). On one hand, chronically stenotic vulnerable plaques are symptomatic lesions that are often treated with Percutaneous Transluminal Intervention (PTI). Unfortunately, approximately 10% of PTI procedures are followed by severe Neointima Hyperplasia (NH), which causes a new occlusion and failure of the implant. A significant precursor …

Neural Processing Of Semantic Content In Movies, Maximilian Nentwich

Dissertations and Theses

Naturalistic stimuli, such as movies, contain interacting, multimodal and semantic features and allow for free exploration through eye movements. The full extent of neural responses to features such as motion, film cuts and eye movement behavior has not been established. The main hypothesis of this thesis is that complex multimodal and semantic stimuli in naturalistic movies engage a widespread ensemble of locations across the entire brain. To address this question I analyzed simultaneous intracranial and eyetracking data from over 6,000 electrodes across 23 patients with intractable epilepsy. Responses to fast eye movements – saccades – and film cuts are widespread …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Osseointegration Of A Cementless Total Knee Arthroplasty In A Murine Model Of Glucocorticoid Induced Osteoporosis, Elexis C. Baral

Dissertations and Theses

Glucocorticoid-Induced Osteoporosis (GIOP) is the second largest cause of osteoporosis worldwide. Glucocorticoid-Induced osteoporosis is rapidly, driven principally by deficient osteoblast activity (i.e., decreased bone formation) rather than increased osteoclastic activity. Glucocorticoid-type steroids (GC) are used long-term typically for inflammatory diseases such as rheumatoid arthritis, lupus, multiple sclerosis, and other autoimmune disorders. Inflammatory arthritis often leads to joint replacement at relatively young ages. However, patients who are on GC treatment appear to have poorer outcomes for total joint arthroplasty compared to healthy patients. This is thought to be due to the anti-anabolic effects of GCs and impaired bone healing and osseous …

Computational Model Of Electroconvulsive Therapy Considering Electric Field Dependent Skin Conductivity, Gozde Unal

Dissertations and Theses

Improvements in electroconvulsive therapy (ECT) outcomes have followed refinement in device electrical output and electrode montage. The physical properties of the ECT stimulus, together with those of the patient’s head, determine the impedances measured by the device and govern current delivery to the brain and ECT outcomes. However, the precise relations among physical properties of the stimulus, patient head anatomy, and patient-specific impedance to the passage of current are long-standing questions in ECT research and practice. In this thesis, we develop a computational framework based on diverse clinical data sets. We developed anatomical MRI-derived models of transcranial electrical stimulation (tES) …

Development Of Cellulose-Based, Semi-Interpenetrating Network Hydrogels As Tissue-Adhesive, Thermoresponsive, Injectable Implants, Jesse Martin

Dissertations and Theses

Abstract Development of Cellulose-Based, Semi-Interpenetrating Network Hydrogels as Tissue-Adhesive, Thermoresponsive, Injectable Implants

Hydrogels are three-dimensional polymer networks with high water content and tunable mechanical properties, which have been widely investigated as replacements for soft tissues, such as the intervertebral disc (IVD). Various derivatives of the plant polysaccharide, cellulose, have been explored for use as injectable hydrogel implants. Methylcellulose (MC), which exhibits thermogelation at temperatures above 32°C, and relatively hydrophilic carboxymethyl-cellulose (CMC), are versatile cellulosic polymers that have shown promise as base materials for such applications. In prior work, functionalization with methacrylate groups allowed for the formation of stable, covalently crosslinked …

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

Dissertations and Theses

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

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

When The Brain Plays A Game: Neural Responses To Visual Dynamics During Naturalistic Visual Tasks, Jason Ki

Dissertations and Theses

Many day-to-day tasks involve processing of complex visual information in a continuous stream. While much of our knowledge on visual processing has been established from reductionist approaches in lab-controlled settings, very little is known about the processing of complex dynamic stimuli experienced in everyday scenarios. Traditional investigations employ event-related paradigms that involve presentation of simple stimuli at select locations in visual space and discrete moments in time. In contrast, visual stimuli in real-life are highly dynamic, spatially-heterogeneous, and semantically rich. Moreover, traditional experiments impose unnatural task constraints (e.g., inhibited saccades), thus, it is unclear whether theories developed under the reductionist …

Restoration Of Bone Material And Microstructural Properties After Long-Term Remodeling Suppression, Abigail A. Coffman

Dissertations and Theses

Anti-resorptive drugs, principally bisphosphonates (BPs), are the mainstay of osteoporosis treatment. They work by inhibiting bone resorption/remodeling, thus preventing bone loss. However, long-term suppression of bone resorption adversely affects bone tissue mechanical properties, even while conserving bone mass. Lack of remodeling leads to accumulation of fatigue-induced microdamage, altered matrix mineralization and reduction in normal bone tissue heterogeneity, causing impaired strength and fracture toughness. The most severe consequence to patients, while rare, is Atypical Femur Fractures (i.e., complete fatigue fractures of the femoral shaft). To counteract the effects of long-term remodeling suppression, a temporary break in BP treatment (a "drug holiday) …

Development Of A Biaxial Testing System For Research Of Soft Tissue Biomechanics Using Laboratory Models, Tariq Shameen

Dissertations and Theses

The rupture of the cap tissue layer of a fibroatheroma in human coronary vessels is considered the key event leading to the formation of a thrombus and myocardial infarction, resulting in more than half a million deaths in the US every year. In this study, we are interested in investigating the biomechanics of different elastomer materials that can be used as laboratory models to replicate coronary arteries’ ultimate tensile stress (0.2 - 2.08 MPa). To this end, we developed a biomechanical testing system that allows us to characterize the material properties of small samples with high accuracy and precision. We …

Osteocyte Activity And Skeletal Muscle Relative Gene Expression Profiling After Short-Term Muscle Paralysis, Michelle Gelbs

Dissertations and Theses

Mechanical loading is essential for maintaining bone tissue. Reduced mechanical loading has been shown to have a negative effect on bone, and can result in the development of disuse osteoporosis. Disuse models of muscle inactivity and immobilization, like the Botox model used in this study, result in changes in the bone microarchitecture, the mechanisms behind which are not fully understood. In a previous four-week Botox disuse study, skeletally mature 20- week-old rats experienced degradation of intracortical bone, increased vascular porosity, and decreased osteocyte lacunar density in the tibiae. The focus of this study was to explicate a potential source of …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Development Of An Injectable Methylcellulose Hydrogel System For Nucleus Pulposus Repair And Regeneration, Nada A. Haq-Siddiqi

Dissertations and Theses

Low back pain is the most common cause of disability in the world and is often caused by degeneration or injury of the intervertebral disc (IVD). The IVD is a complex, fibrocartilaginous tissue that allows for the wide range of spinal mobility. Disc degeneration is a progressive condition believed to begin in the central, gelatinous nucleus pulposus (NP) region of the tissue, for which there are few preventative therapies. Current therapeutic strategies include pain management and exercise, or surgical intervention such as spinal fusion, none of which address the underlying cause of degeneration. With an increasingly aging population, the socioeconomic …

Optimized Xanthene-Based Probes For Pancreatic Cancer Imaging, Ian Ruramai Munhenzva

Dissertations and Theses

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest human malignancies with an extremely poor 5-year survival rate of below 5%. Surgical resection is the most effective treatment of choice because chemotherapy and radiation therapy do not improve life expectancy. Residual tumor after PDAC surgery is common due to a lack of PDAC targeted intraoperative contrast agents to confirm clear margins.

Fluorescence imaging has the potential to improve surgery outcome and PDAC patients' survival rate via the use of highly PDAC-specific molecular probes to facilitate tumor identification. This thesis describes the application of a focused library of benzoxanthene fluorophores for …

Attention Strongly Modulates Reliability Of Neural Response To Naturalistic Narrative Stimuli, Jason Ki

Dissertations and Theses

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content we are presented with through modern media, there is increased variability in the degree to which we ‘absorb’ that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger …

Diffuse Damage Repair Mechanism In Bone, Leila Mehraban Alvandi

Dissertations and Theses

Bone microdamage is a result of fatigue, creep or ‘wear and tear’ caused by physiological activities and largely contributes to bone fragility. Bone, unlike engineered materials, has the ability to repair the microscopic cracking or microdamage through targeted, osteoclast-mediated bone remodeling. This capability is crucial for preservation of its structural integrity and quality; failure of the skeleton to effectively repair microdamage leads to accumulation of damage, which is one of the main contributors to bone fragility. Linear microcracks (50-100 µm) and diffuse damage (Dif.Dx) (sub-micron) are the two types of microdamage. Recent studies show that Dif.Dx repairs without bone remodeling, …

Effects Of Weak Electric Fields On Long-Term Synaptic Plasticity, Gregory Kronberg

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a technique where a weak direct electrical current is applied to the scalp with the goal of stimulating the brain. There is tremendous interest in the use of tDCS for treating brain disorders and improving brain function. However, the effects of tDCS have been highly variable across studies, leading to a debate over its efficacy. A major challenge is therefore to design tDCS protocols that yield predictable effects, which will require a better understanding of its basic mechanisms of action. One commonly discussed mechanism is that tDCS may alter synaptic plasticity, but the biophysics …

Influence Of Transdermal Current Flow In Tdcs-Induced Cutaneous Adverse Events, Niranjan Khadka

Dissertations and Theses

Significant contributors to the broad application of transcranial direct current stimulation (tDCS) are portability, ease-of-use, and tolerability; with adverse events limited to transient and mild cutaneous sensations (e.g. perception of burning, itching, and tingling) and erythema. However, the fundamental questions remain about the mechanism of transdermal current flow during transcranial electrical stimulation, including tDCS. Example of previously unexplained questions in tDCS include: 1) the relationship between tDCS-induced skin reddening (erythema) profile and local current density profile predicted by the model; 2) the source of burning sensation during tDCS and whether it is related to an actual skin heating; 3) the …

Characterization Of Bone Pathology In Sickle Cell Disease And Therapeutic Strategies, Mykel D. Green

Dissertations and Theses

Sickle cell disease (SCD) is a genetic hemoglobinopathy that has grown into a global health concern. While the advances in medical treatment and management of SCD during childhood have drastically improved the overall survival of children, the transition from pediatric to adult services is significantly inadequate in comparison. Life expectancies of patients with SCD in first world countries such as the United States are shortened to averages of 42 and 48 years for men and women, respectively. Despite the increasing number of people living with SCD, remarkably, few detailed studies have described the clinical course and complications of the disease …

A Microfluidic Tissue Array (Μfta) For Personalized Medicine Using Tumor Biopsies, A.H. R. Ahmed

Dissertations and Theses

Cancer is recognized as a complex disease with both genetic and epigenetic drivers that can vary from one individual to another. While very early research into cancer treated it as a clonal malfunction that could originate from as small as a single deregulated cell, the disease itself manifests itself with several more complexities beyond tumorigenic cells only. The tumor microenvironment itself – from the extracellular matrix to stromal cells - cooperate with tumor cells in a symbiotic manner towards metastatic progression. Clinical studies have provided more information regarding the degree of individualization possible, such that patients with similar genetic makeup …

Controlled Migration Of Retinal Progenitor Cells Within Electro-Chemotactic Fields, Shawn Mishra

Dissertations and Theses

Vision loss in retinal degenerative diseases is overwhelmingly attributed to damage and death of retinal photoreceptor cells. Studies in mouse retina have suggested that transplantation of isolated post-natal or stem cell-derived retinal progenitor cells (RPCs) to replace apoptotic or damaged photoreceptors may be a novel approach to restore vision. Thus far, outcomes project that the amount of restored visual response depends upon the migration of transplanted cells from insertion in the sub-retinal space to the outer nuclear layer (ONL). However, transplantation efficiency is exceedingly low – ~5% cells transplanted enter the retina – directly limiting the efficacy of the treatments. …

Neuron-Glial (Ng) Interactions: A Microfluidic Examination Of Ng Emergent Responses For Repair, Tanya Singh

Dissertations and Theses

Neuron-glia communication is crucial to the development, plasticity, and repair of the nervous system (NS). While neurons are well known to conduct electrical impulses that transfer biological information and stimuli throughout the NS, our understanding of the roles of glia continues to evolve from when the cells were largely believed to act solely for neuronal support. Recent decades of research has shown that glia can alter metabolism, conduct impulses and change phenotype for NS repair. NG interactions have, thereby, become heavily researched in varied areas of biomedical engineering, including embryogenesis, neural regeneration, growth, and intracellular synaptic activity. However, while NG …