Biomedical Engineering and Bioengineering Commons^™

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 …

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on …

Investigating Cyanobacteria Metabolism And Channeling-Based Regulations Via Isotopic Nonstationary Labeling And Metabolomic Analyses, Mary Helen Abernathy

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cyanobacteria have the potential to be low-cost and sustainable cell factories for bio-products; however, many challenges face cyanobacteria as biorefineries. This dissertation seeks to advance non-model photosynthetic organisms for biotechnology applications by characterizing central carbon metabolism and its regulations. Cyanobacteria phenotypes for bio-production are examined and their intracellular metabolism is quantified. Using isotopic labeling experiments, phenotypic relationships between biomass composition, central carbon fluxes, and metabolite pool sizes are investigated. Metabolic analyses of cyanobacteria led to new investigations of flux regulation mechanisms via protein spatial organizations or metabolite channeling. Metabolite channeling is further explored as a hypothesis to explain enigmatic labeling …

Molecular Basis Of Class Ib Drug Interactions With The Nav Channel Macromolecular Complex: A Route To Personalized Medicine For Cardiac Arrhythmia, Wandi Zhu

McKelvey School of Engineering Graduate Student Theses & Dissertations

The heart rhythm is precisely controlled by the electrical impulse that propagate in the cardiac tissue. In single cardiomyocytes, the electrical activity generated by action potentials (AP). Cardiac NaV channels (NaV1.5) carry a large influx of Na+ that mediates the initiation and propagation of the AP in both atria and ventricles. Disruption of NaV1.5 function by genetic variants or external factors can result in deadly arrhythmias, such as long QT syndrome and Brugada syndrome. Thus, NaV channels are import therapeutic targets. The class I antiarrhythmics are the modulators of the NaV channels. Although they have been used clinically for over …

Basis Vector Model Method For Proton Stopping Power Estimation Using Dual-Energy Computed Tomography, Shuangyue Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate estimation of the proton stopping power ratio (SPR) is important for treatment planning and dose prediction for proton beam therapy. The state-of-the-art clinical practice for estimating patient-specific SPR distributions is the stoichiometric calibration method using single-energy computed tomography (SECT) images, which in principle may introduce large intrinsic uncertainties into estimation results. One major factor that limits the performance of SECT-based methods is the Hounsfield unit (HU) degeneracy in the presence of tissue composition variations. Dual-energy computed tomography (DECT) has shown the potential of reducing uncertainties in proton SPR prediction via scanning the patient with two different source energy spectra. …

Acetylation Profiles Of Histone And Non-Histone Proteins In Breast Cancer, Alla Karpova

McKelvey School of Engineering Graduate Student Theses & Dissertations

This study evaluates the impact of protein acetylation on breast cancer gene expression and the regulation of metabolism. Acetylation is the second abundant post-translational modification after phosphorylation, regulating protein activity and function. The alterations in acetylation of both histone and non-histone proteins is known to be related to many human diseases, including cancer. Acetylation and deacetylation of histones is closely associated with the regulation of gene expression, while acetylation of non-histone proteins may have a broad effect on major cellular processes, such as proliferation, metabolism, cell cycle and apoptosis, imbalanced regulation of which is essential for cancer development. Therefore, it’s …

Numerical Simulation And Optimization Of Blalock-Taussig Shunt, Thomas Hess, Ramesh K. Agarwal

McKelvey School of Engineering Graduate Student Theses & Dissertations

The goal of this study is to create an optimized Blalock-Taussig shunt used to temporarily repair pulmonary vascular blockages allowing a child time to grow so a more permanent surgical repair of the heart and vasculature can be performed. Blalock-Taussig or BT shunts are a surgical procedure performed on infants suffering from cyanosis or “Blue Baby Syndrome.” A BT shunt is an artificial vessel placed between the right ventricle and the pulmonary artery to increase blood flow in the lung and blood oxygen saturation levels. In a study of 96 patients with currently in use modified BT shunts, 32 patients …

Controlling The Oxygen Microenvironment: The Role Of Hif-1Α In Early Tumor Progression, Sandra Lam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cancer drug efficacy has remained a critical obstacle for researchers as it has one of the lowest probabilities of success compared to other diseases. One method to help improve this success rate is to create better tumor models on which to perform the drug testing. With growing interesting in microphysiological systems, scientists can create more advanced in vitro models of human organ systems as well as diseased states. These “organ-on-a-chip” platforms aim to improve drug response prediction for both efficacy and toxicity. One underappreciated characteristic of many disease states is that they are often at a lower oxygen tension that …

Assessment And Diagnosis Of Human Ovarian And Colorectal Cancer Using Optical And Photoacoustic Imaging, Sreyankar Nandy

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical imaging modalities have the advantage of high resolution, label free, rapid, low cost imaging for both in vivo and ex vivo diagnosis of biological tissues. Optical scattering, which is the main contrast of optical coherence tomography (OCT), is related to elastic scattering components, mainly stromal collagen. Tissue elasticity has recently emerged as an important diagnostic parameter associated with tumor development and progression and is also related to the distribution of structural components such as tissue collagen. We have used an optical coherence tomography elastography (OCTE) system for characterizing the differences in the micro-mechanical properties of benign and malignant human …

Engineering Robust And Programmable Biological Systems, Tatenda Shopera

McKelvey School of Engineering Graduate Student Theses & Dissertations

The ability to engineer programmable biological systems using complex artificial gene networks has great potential to unlock important innovative solutions to many biotechnological challenges. While cells have been engineered to implement complex information processing algorithms and to produce food, materials, and pharmaceuticals, many innovative applications are yet to be realized due to our poor understanding of how robust, reliable, and predictable artificial gene circuits are built. In this work, we demonstrate that robust complex cellular behaviors (e.g., bistability and gene expression dynamics) can be achieved by engineering gene regulatory architecture and increasing the complexity of genetic networks. We further demonstrate …

Mathematical Models Of Innate Immune Cell Signaling Networks Using Protein Phosphorylation Patterns, Allison Anne Throm

McKelvey School of Engineering Graduate Student Theses & Dissertations

Immune dysregulation has been implicated in pediatric autoimmune disease

pathogenesis, but the underlying mechanisms still remain poorly understood. We explored

immune cell signaling dysregulation in two different pediatric autoimmune diseases:

polyarticular juvenile idiopathic arthritis (JIA), a disease characterized by pain, swelling, and

limited range of motion in five or more joints and juvenile dermatomyositis (JDM), a disease

characterized by pathognomonic skin rashes and proximal muscle weakness. Both polyarticular

JIA and JDM can be controlled with newer biologic medications, but a substantial fraction of

patients still experiences refractory disease courses. To explore potential immune cell signaling

dysregulation, mass cytometry was performed …

Noninvasive Multi-Modality Studies Of Cardiac Electrophysiology, Mechanics, And Anatomical Substrate In Healthy Adults, Arrhythmogenic Cardiomyopathy, And Heart Failure, Christopher Andrews

McKelvey School of Engineering Graduate Student Theses & Dissertations

Heart disease is a leading cause of death and disability and is a major contributor to healthcare costs. Many forms of heart disease are caused by abnormalities in the electrical function of heart muscle cells or the cardiac conduction system. Electrocardiographic Imaging (ECGI) is a noninvasive modality for imaging cardiac electrophysiology. By combining recordings of the voltage distribution on the torso surface with anatomical images of the heart-torso geometry, ECGI reconstructs voltages on the epicardium. This thesis applies ECGI to novel studies of human heart function and disease and explores new combinations of ECGI with additional imaging modalities.

ECGI was …

Brain-Computer Interfaces Using Electrocorticography And Surface Stimulation, Jesse Wheeler

McKelvey School of Engineering Graduate Student Theses & Dissertations

The brain connects to, modulates, and receives information from every organ in the body. As such, brain-computer interfaces (BCIs) have vast potential for diagnostics, medical therapies, and even augmentation or enhancement of normal functions. BCIs provide a means to explore the furthest corners of what it means to think, to feel, and to act—to experience the world and to be who you are. This work focuses on the development of a chronic bi-directional BCI for sensorimotor restoration through the use of separable frequency bands for recording motor intent and providing sensory feedback via electrocortical stimulation. Epidural cortical surface electrodes are …

Radiological Pathological Correlations In Chronic Traumatic Encephalopathy, Mihika Gangolli

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that has been increasingly linked to traumatic brain injury. The neuropathology that distinguishes CTE from other tauopathies includes hyperphosphorylated tau (pTau) tangles and tau positive astrocytes irregularly distributed in cortical sulcal depths and clustered around perivascular foci. These features are clearly identified using immunohistochemistry, but are undetectable to current clinical imaging methods. Diffusion imaging has been proposed as a noninvasive method to detect the pathognomonic lesion of CTE in vivo because of its high sensitivity to microstructural alterations in tissue structure. While several diffusion imaging approaches, ranging from diffusion tensor imaging …