Biomedical Engineering and Bioengineering Commons^™

Tissue Engineering Of Induced Pluripotent Stem Cells For The Development Of Novel Treatment Strategies For Osteoarthritis, Alison Ross

McKelvey School of Engineering Graduate Student Theses & Dissertations

Osteoarthritis (OA) is a debilitating joint disease that is primarily characterized by the degeneration of articular cartilage, the soft connective tissue that covers articulating bone surfaces in diarthrodial joints. While there are a number of risk factors for developing OA, the progression of this disease is mediated in part by pro-inflammatory cytokines from both the synovium and chondrocytes, the resident cells of articular cartilage. These cytokines, specifically interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α), induce aberrant expression of catabolic and degradative enzymes and inflammatory cytokines in OA, which promotes degradation of engineered tissues as well as native articular …

Ultrasound Guided Diffuse Optical Tomography For Breast Cancer Diagnosis: Algorithm Development, K M Shihab Uddin

McKelvey School of Engineering Graduate Student Theses & Dissertations

According to National Breast Cancer Society, one in every eight women in United States is diagnosed with breast cancer in her lifetime. American Cancer Society recommends a semi-annual breast-cancer screening for every woman which can be heavily facilitated by the availability of low-cost, non-invasive diagnostic method with good sensitivity and penetration depth. Ultrasound (US) guided Diffuse Optical Tomography (US-guided DOT) has been explored as a breast-cancer diagnostic and screening tool over the past two decades. It has demonstrated a great potential for breast-cancer diagnosis, treatment monitoring and chemotherapy-response prediction. In this imaging method, optical measurements of four different wavelengths are …

Exploring Attacks And Defenses In Additive Manufacturing Processes: Implications In Cyber-Physical Security, Nicholas Deily

McKelvey School of Engineering Graduate Student Theses & Dissertations

Many industries are rapidly adopting additive manufacturing (AM) because of the added versatility this technology offers over traditional manufacturing techniques. But with AM, there comes a unique set of security challenges that must be addressed. In particular, the issue of part verification is critically important given the growing reliance of safety-critical systems on 3D printed parts. In this thesis, the current state of part verification technologies will be examined in the con- text of AM-specific geometric-modification attacks, and an automated tool for 3D printed part verification will be presented. This work will cover: 1) the impacts of malicious attacks on …

Ultrasensitive Biodetection Based On Plasmonically-Active Materials, Jingyi Luan

McKelvey School of Engineering Graduate Student Theses & Dissertations

A broad range of biomarkers continue to emerge as potentially important parameters for early detection of many pathological conditions.1 A disease biomarker (e.g. protein, a fragment of a pro-tein, DNA/RNA, or metabolites) is a ‘molecular signature’ of the physiological state of patient at specific time and is therefore extremely important for early and possibly pre-symptomatic diagno-sis and accurate monitoring of therapeutic intervention. Relevant concentrations of biomarkers related to diseases such as cancer, heart disease, inflammation, and neurological disorders can range in many orders of magnitude from μg/ml levels to sub-fg/ml, some of which possibly still remain unidentified due to the …

The Mechanobiology Of Elbow Contracture: Pathogenesis And Prevention, Chelsey Dunham

McKelvey School of Engineering Graduate Student Theses & Dissertations

Post-traumatic elbow contracture is a multi-tissue pathology which develops in up to 50% of patients following elbow trauma (e.g., fracture, dislocation). It is unclear which periarticular soft tissues are driving the functional deficit following injury because it is not possible in clinical settings to isolate each soft tissues’ mechanical and biological contributions to elbow contracture. Therefore, an animal model is needed to identify the primary periarticular soft tissue(s) which contribute to contracture. The first animal models of contracture were developed in the knee; however, these studies are not generalizable to the elbow due to anatomical and functional differences between these …

Toward Controlling Cardiac Tissue Pacing Using Modified Mrna, Yicheng Zhao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Arrhythmia is a common heart disease that happens when the heart is beating too fast, too slow, or irregularly. To study the mechanisms and treatments of this disease, it is important to acutely control the beating rate of the model as it will help distinguish the contribution of different potassium currents and drug-induced action potential in cardiomyocytes. The current method of tissue pacing, electrical pacing, causes contamination and corrosive damage to tissues, thus the tissues fail to be used repeatedly or in future studies. In this study, red-shifted channelrhodopsin (ReaChR) is applied as a non-chemical means to control the beating …

Transcriptomic Analysis Of Cytokine-Treated Tissue-Engineered Cartilage As An In Vitro Model Of Osteoarthritis, Jiehan Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

Osteoarthritis (OA), as the most common form of arthritis and a leading cause of disability worldwide, currently has no disease-modifying drugs. Inflammation plays an important role in cartilage degeneration in OA, and pro-inflammatory cytokines, IL-1β and TNF-α, have been shown to induce degradative changes along with aberrant gene expression in chondrocytes, the only resident cells in cartilage. The goal of this study was to further understand the transcriptomic regulation of tissue-engineered cartilage in response to inflammatory cytokines using an in vitro miPSC model system. We performed RNA sequencing for the IL-1β or TNF-α treated tissue-engineered cartilage derived from murine iPSCs, …

Design And Validation Of A Dynamic Pressure-Based Loading Device And 3d Strain Tracking Protocol For Ventral Hernia Modeling, Griffin Kivitz

McKelvey School of Engineering Graduate Student Theses & Dissertations

It is estimated that 350,000-500,000 ventral hernia repair surgeries are performed each year in the United States. While the long-term recurrence rate of ventral hernia repairs is not yet known, when tissues are exposed to the trauma of surgery, there is always the chance of recurrence. Commonly used ex vivo testing methods for determining the mechanical properties of the abdominal wall and biomaterials for hernia repair consist primarily of uniaxial and biaxial testing, which are not physiologically relevant loading environments. The need for a testing device that can exert physiologically relevant loads ex vivo to an abdominal wall is crucial …

A High Frequency Photoacoustic System For Colorectal Cancer Imaging, Kexin Huang

McKelvey School of Engineering Graduate Student Theses & Dissertations

While colorectal cancer is the second largest cause of cancer-related deaths in the United States, early detection is a key factor in its survival rate. Compared to conventional imaging modalities, photoacoustic imaging offers benefits in providing angiographic images which are valuable for early-stage tumor detection. This thesis presents the design of a 32-channel 80 MHz photoacoustic image system, whose relatively high frequency offers particular advantages. The system comprises several modules, including a laser system, ultrasound probe, AD convertor, microcontroller (FPGA), and a computer. The system requires programs for the FPGA and the data receiver on the computer. The data transportation …

Computational Imaging Methods For Analysis Of Datscan Spect Images, Hae Sol Moon

McKelvey School of Engineering Graduate Student Theses & Dissertations

There is an important need to develop biomarkers to improve the diagnosis and assess the severity of Parkinson’s disease (PD). The potential to derive such biomarkers from quantitative dopamine transporter scan (DaT-Scan) single-photon emission computed tomography (SPECT) imaging, in particular the uptake of DaT in the caudate, putamen, and globus pallidus regions, is highly appealing as imaging is non-invasive and DaTScan is already used in the management of patients with PD. However, reliable quantification requires reliable segmentation of these regions in these images. Reliable segmentation is challenging due to the limited spatial resolution and high image noise in SPECT images …

Development Of High-Speed Photoacoustic Imaging Technology And Its Applications In Biomedical Research, Yun He

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of …

Rhodococcus Opacus Pd630 Genetic Tool Development To Enable The Conversion Of Biomass, Drew Michael Delorenzo

McKelvey School of Engineering Graduate Student Theses & Dissertations

The discovery of fossil fuels facilitated a new era in human history and allowed many firsts, such as the mass production of goods, the ability to travel and communicate long distances, the formation of population dense cities, and unprecedented improvements in quality of life. Alternative sources of energy and chemicals are needed, however, as hydrocarbon reserves continue to deplete and the effects of burning fossils on the planet become better understood. Lignocellulosic biomass is the most abundant raw material in the world and a viable alternative to petroleum-derived products. The pre-treatment of lignocellulose (e.g., thermocatalytic depolymerization, enzymatic hydrolysis, pyrolysis, etc.) …

Three-Dimensional Image Reconstruction In Transcranial Photoacoustic Computed Tomography, Joemini Poudel

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic computed tomography (PACT) is an emerging imaging modality that exploitsoptical contrast and ultrasonic detection principles to form images of the photoacousticallyinduced initial pressure distribution within tissue. The PACT reconstruction problemcorresponds to an inverse source problem in which the initial pressure distribution is recoveredfrom measurements of the radiated pressure wavefield. A major challenge in transcranialPACT brain imaging is compensation for aberrations in the measured data due to the presenceof the skull. Ultrasonic waves undergo absorption, scattering and longitudinal-to-shear wavemode conversion as they propagate through the skull. To properly account for these effects, awave-equation-based inversion method should be employed that can …

Ph-Sensitive Oxygen Release Microspheres To Enhance Cell Survival In Ischemic Condition, Zhongting Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Ischemic diseases such as myocardial infarction, stroke and limb ischemia are severe cardiovascular diseases with high rate of death and millions of people suffered from these diseases. Under ischemic environment, cells die due to deficient supply of nutrient and oxygen. To regenerate ischemic tissues, stem cell therapy is a promising approach because stem cells can differentiate into cells necessary for the regeneration. However, stem cell therapy has limitations. For example, few cells can survive under harsh ischemic environment. To enhance stem cells survival, implantation of oxygen release microspheres to sustained supply cells with oxygen represents an effective strategy. Previously, our …

Multi-Dimensional Extension Of The Alternating Minimization Algorithm In X-Ray Computed Tomography, Jingwei Lu

McKelvey School of Engineering Graduate Student Theses & Dissertations

X-ray computed tomography (CT) is an important and effective tool in medical and industrial

imaging applications. The state-of-the-art methods to reconstruct CT images have had

great development but also face challenges. This dissertation derives novel algorithms to

reduce bias and metal artifacts in a wide variety of imaging modalities and increase performance

in low-dose scenarios.

The most widely available CT systems still use the single-energy CT (SECT), which is

good at showing the anatomic structure of the patient body. However, in SECT image

reconstruction, energy-related information is lost. In applications like radiation treatment

planning and dose prediction, accurate energy-related information …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Graduate Student Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Understanding Excitation Energy Quenching In Isia, Hui-Yuan Steven Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cyanobacteria are photoautotrophic organisms that contribute a significant amount of global primary productivity. They are found in freshwater, marine and even some extremely severe environments. Among those environments, iron deficiency is one of the most common stress conditions in cyanobacterial habitats. To survive, cyanobacteria have evolved and developed several strategies to alleviate the damage caused by iron deficiency.

Iron stress-inducible protein (IsiA) is a chlorophyll-binding membrane protein found in cyanobacteria grown in iron-deficient conditions. During the past decades, considerable effort has been put on understanding how IsiA functions to help cyanobacteria survive iron deficiency. It has been reported that IsiA …

Multi-Dimensional Extension Of The Alternating Minimization Algorithm In X-Ray Computed Tomography, Jingwei Lu

McKelvey School of Engineering Graduate Student Theses & Dissertations

X-ray computed tomography (CT) is an important and effective tool in medical and industrial imaging applications. The state-of-the-art methods to reconstruct CT images have had great development but also face challenges. This dissertation derives novel algorithms to reduce bias and metal artifacts in a wide variety of imaging modalities and increase performance in low-dose scenarios. The most widely available CT systems still use the single-energy CT (SECT), which is good at showing the anatomic structure of the patient body. However, in SECT image reconstruction, energy-related information is lost. In applications like radiation treatment planning and dose prediction, accurate energy-related information …

Joint Reconstruction For Single-Shot Edge Illumination Phase-Contrast Tomography (Eixpct), Yujia Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Edge illumination X-ray phase-contrast tomography (EIXPCT) is an emerging X-ray phasecontrast tomography technique for estimating the complex-valued X-ray refractive index distribution of an object with laboratory-based X-ray sources. Conventional image reconstruction approaches for EIXPCT require multiple images to be acquired at each tomographic view angle. This contributes to prolonged data-acquisition times and elevated radiation doses, which can hinder in vivo applications. In this dissertation, a new “single-shot” method without restrictive assumptions related to the object, imaging geometry or hardware is proposed for joint reconstruction (JR) of the real and imaginary-valued components of the refractive index distribution from a tomographic data …

A Modular Approach For Modeling, Detecting, And Tracking Freezing Of Gait In Parkinson Disease Using Inertial Sensors, Prateek Gundannavar Vijay

McKelvey School of Engineering Graduate Student Theses & Dissertations

Parkinson disease, the second most common neurodegenerative disorder, is caused by the loss of dopaminergic subcortical neurons. Approximately 50% of people with Parkinson disease experience freezing of gait (FOG), a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. FOG causes falls and is resistant to medication in more than 50% of cases. FOG episodes can often be interrupted by mechanical interventions (e.g., a verbal reminder to march), but it is often not practical to apply these interventions on demand (e.g., there is not usually another person to detect an FOG episode …

Mechanosensitive Epithelial Cell Scattering And Migration On Layered Matrices, Christopher Michael Walter

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epithelial cells form multi-layered tissue scaffolding that makes up every organ in the body. Along with epithelial cells, the basement membrane (BM) and connective tissue are composed of various proteins that sculpt the organs and protect them from foreign macromolecules. Epithelial cells respond to various cues, both chemical and mechanical, from their surrounding matrices to aid in maintenance and repair of these layers through degradation and deposition of extracellular matrix (ECM) proteins. In cancer progression, epithelial cells lose their normal function of supporting tissue structure and instead adopt more aggressive behaviors through an epithelial-to-mesenchymal transition (EMT) of their cellular traits. …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Graduate Student Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Improved Orthopaedic Repairs Through Mechanically Optimized, Adhesive Biomaterials, Stephen Wheeler Linderman

McKelvey School of Engineering Graduate Student Theses & Dissertations

Despite countless surgical advances over the last several decades refining surgical approaches, repair techniques, and tools to treat tendon and tendon-to-bone injuries, we are still left with repair solutions that rely on fairly crude underlying mechanical principles. Musculoskeletal soft tissues have evolved to transfer high loads by optimizing stress distribution profiles across the tissue at each length scale. However, instead of mimicking these natural load transfer mechanisms, conventional suture approaches are limited by high load transfer across only a small number of anchor points within tissue. This leads to stress concentrations at anchor points that often cause repair failure as …

Approaches To Understanding The Function Of Intrinsic Activity And Its Relationship To Task-Evoked Activity In The Human Brain, Dohyun Kim

McKelvey School of Engineering Graduate Student Theses & Dissertations

Traditionally neuroscience research has focused on characterizing the topography and patterns of brain activation evoked by specific cognitive or behavioral tasks to understand human brain functions. This activation-based paradigm treated underlying spontaneous brain activity, a.k.a. intrinsic activity, as noise hence irrelevant to cognitive or behavioral functions. This view, however, has been profoundly modified by the discovery that intrinsic activity is not random, but temporally correlated at rest in widely distributed spatiotemporal patterns, so called resting state networks (RSN). Studies of temporal correlation of spontaneous activity among brain regions, or functional connectivity (FC), have yielded important insights into the network organization …

Ultrasound-Guided Optical Techniques For Cancer Diagnosis: System And Algorithm Development, Atahar Kamal Mostafa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Worldwide, breast cancer is the most common cancer among women. In the United States alone, the American cancer society has estimated there will be 271,270 new breast cancer cases in 2019, and 42,260 lives will be lost to the disease. Ultrasound (US), mammography, and magnetic resonance imaging (MRI) are regularly used for breast cancer diagnosis and therapy monitoring. However, they sometimes fail to diagnose breast cancer effectively. These shortcomings have motivated researchers to explore new modalities. One of these modalities, diffuse optical tomography (DOT), utilizes near-infrared (NIR) light to reveal the optical properties of tissue. NIR-based DOT images the contrast …

Elucidating The Roles Of Astrocyte-Derived Factors In Recovery And Regeneration Following Spinal Cord Injury, Russell E. Thompson

McKelvey School of Engineering Graduate Student Theses & Dissertations

Central nervous system (CNS) injury often causes some level of long-term functional deficit, due to the limited regenerative potential of the CNS, that results in a decreased quality of life for patients. CNS regeneration is inhibited partly by the development of a glial scar following insult that is inhibitory to axonal growth. The major cell population responsible for the formation this glial scar are astrocytes, which has led to the belief that astrocytes are primarily inhibitory following injury. Recent work has challenged this conclusion, finding that astrocyte reactivity is heterogeneous and that some astrocytes are pro-regenerative following injury. Astrocyte transplantation …

A High-Throughput Screening Platform For In Vitro Elastic Fiber Production And The Mass Transport Properties Of The Elastic Fiber Compromised Arterial Wall, Austin John Cocciolone

McKelvey School of Engineering Graduate Student Theses & Dissertations

Elastin comprises nearly 50% of the wall in large elastic arteries and has a broad variety of physiological roles. As a structural extracellular matrix protein, elastin is responsible for the reversible elasticity in large arties that dampens pulsatile flow and ultimately reduces the workload on the heart. Structural compromise to the elastic fiber network is apparent in the elastin genetic disorders, supravalvular aortic stenosis and autosomal dominant cutis laxa-1, and acquired elastin disorders including hypertension, atherosclerosis, artery calcification, aneurysms, diabetes, and obesity. All of these disorders lead to an increased incidence of cardiovascular related death and the compromised elastic fiber …

Preclinical Imaging Of Multiple Myeloma Therapy Response, Deep Hathi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Multiple myeloma (MM) is a debilitating hematologic malignancy of terminally differentiated plasma cells in the bone marrow (BM). Advances in therapeutic regimens and the use of autologous stem cell transplantation have significantly improved survival rates and quality of life in patients. However, the disease remains incurable, with shorter, successive remission cycles following relapse. To reduce systemic, off-target toxicity and improve quality of life, there is a need for improved stratification of responding patients. Identification of specific, noninvasive, imaging biomarkers that correlate to therapeutic efficacy is an attractive strategy for stratifying responding patients, since the use of positron emission tomography (PET), …

Regularized Fourier Ptychographic Microscopy, Shiqi Xu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Quantitative phase image (QPI) is a popular microscopy technique for studying cell morphology. Recently, Fourier ptychographic microscopy (FPM) has emerged as a low-cost computational microscopy technique for forming high-resolution wide-field QPI images by taking multiple images from different illumination angles. However, the applicability of FPM to dynamic imaging is limited by its high data requirement. In this thesis, we propose new methods for highly compressive FPM imaging using a data-adaptive sparse coding and an online plug-and-play (PnP) method with non-local priors based on the fast iterative shrinkage/threshold algorithm (FISTA). We validate the proposed method on both simulated and experimental data …

Long-Term, Super-Resolution Imaging Of Amyloid Structures Using Transient Amyloid Binding Microscopy, Tianben Ding, Kevin Spehar, Jan Bieschke, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid fibrils and tangles are signatures of Alzheimer disease, but nanometer-sized aggregation intermediates are hypothesized to be the structures most toxic to neurons. The structures of these oligomers are too small to be resolved by conventional light microscopy. We have developed a simple and versatile method, called transient amyloid binding (TAB), to image amyloid structures with nanoscale resolution using amyloidophilic dyes, such as Thioflavin T, without the need for covalent labeling or immunostaining of the amyloid protein. Transient binding of ThT molecules to amyloid structures over time generates photon bursts that are used to localize single fluorophores with nanometer precision. …