Biomedical Engineering and Bioengineering Commons^™

Development And Evaluation Of Biocompatible Engineered Nanoparticles For Use In Ophthalmology, Bedia Begum Karakocak

McKelvey School of Engineering Graduate Student Theses & Dissertations

The synthesis and design of biocompatible nanoparticles for targeted drug delivery and bioimaging requires knowledge of both their potential toxicity and their transport. For both practical and ethical reasons, evaluating exposure via cell studies is a logical precursor to in vivo tests. As a step towards clinical trials, this work extensively investigated the toxicity of gold nanoparticles (Au NPs) and carbon dot (CD) nanoparticles as a prelude to their in vivo application, focusing specifically on ocular cells. As a further step, it also evaluated their whole-body transport in mice. The research pursued two approaches in assessing the toxicity of engineered …

Hemodynamic Effects On Embryonic Arterial Growth And Matrix Remodeling, Maria Gabriela Espinosa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Hemodynamic forces drive cardiovascular morphogenesis and remodeling in the developing embryo. Changes to the embryonic hemodynamic environment have been shown to induce a variety of congenital heart defects, but little attention has been given to vasculature-specific defects. Although vascular development has been widely studied in the context of genetics and molecular biology, this work investigates the impact of hemodynamic forces on arterial development and mechanics.

The dorsal aorta (DA) is the first intraembryonic vessel to form. Its passive mechanical properties are determined by the deposition of extracellular matrix (ECM) proteins, a hallmark of arterial maturation. We hypothesized that hemodynamic changes …

Forward Electrophysiological Modeling And Inverse Problem For Uterine Contractions During Pregnancy, Mengxue Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Uterine contractile dysfunction during pregnancy is a significant healthcare challenge that imposes heavy medical and financial burdens on both human beings and society. In the U.S., about 12% of babies are born prematurely each year, which is a leading cause of neonatal mortality and increases the possibility of having subsequent health problems. Post-term birth, in which a baby is born after 42 weeks of gestation, can cause risks for both the newborn and the mother. Currently, there is a limited understanding of how the uterus transitions from quiescence to excitation, which hampers our ability to detect labor and treat major …

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

Chronic Nerve Interfacing Utilizing Graft-Embedded Regenerative Macro-Sieve Electrodes, Amrita Nishtala

McKelvey School of Engineering Graduate Student Theses & Dissertations

Custom-designed macro-sieve electrodes represent a novel means of facilitating chronic high specificity nerve stimulation needed to control distal nerve musculature and restore sensorimotor function. Implantation of these electrodes requires the transection of the nerve, which has shown to disrupt muscle fiber distribution. This present study assesses the feasibility of implementing these electrodes in an end-to-side nerve graft. The macro-sieve electrodes were fabricated and micro-surgically implanted into 3.2 cm nerve autografts harvested from the sciatic nerve of 12 male Lewis rats. Electrode-enabled nerve grafts were micro-surgically implanted in an end-to-side manner into donor rat sciatic nerves without the need for a …

Developing Wavefront Shaping Techniques For Focusing Through Highly Dynamic Scattering Media, Ashton Hemphill

McKelvey School of Engineering Graduate Student Theses & Dissertations

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit of ~1 mm in soft tissue. This greatly restricts the utility of optical diagnostic and therapeutic techniques, such as optogenetics, microsurgery, optical tweezing, and phototherapy of deep tissue, which require focused light in order to function. Wavefront shaping extends the depth at which optical focusing may be achieved by compensating for phase distortions induced by scattering, allowing for focusing through constructive interference.

However, due to physiological motion, scattering of light …

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for …

Functional Electrical Stimulation Of Peripheral Nerve Tissue Via Regenerative Sieve Microelectrodes, Matthew Reagan Macewan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Functional electrical stimulation (FES) of peripheral nervous tissue offers a promising method for restoring motor function in patients suffering from complex neurological injuries. However, existing microelectrodes designed to stimulate peripheral nerve are unable to provide the type of stable, selective interface required to achieve near-physiologic control of peripheral motor axons and distal musculature. Regenerative sieve electrodes offer a unique alternative to such devices, achieving a highly stable, selective electrical interface with independent groups of regenerated nerve fibers integrated into the electrode. Yet, the capability of sieve electrodes to functionally recruit regenerated motor axons for the purpose of muscle activation remains …

Photoacoustic Elastography And Next-Generation Photoacoustic Tomography Techniques Towards Clinical Translation, Pengfei Hai

McKelvey School of Engineering Graduate Student Theses & Dissertations

Ultrasonically probing optical absorption, photoacoustic tomography (PAT) combines rich optical contrast with high ultrasonic resolution at depths beyond the optical diffusion limit. With consistent optical absorption contrast at different scales and highly scalable spatial resolution and penetration depth, PAT holds great promise as an important tool for both fundamental research and clinical application. Despite tremendous progress, PAT still encounters certain limitations that prevent it from becoming readily adopted in the clinical settings. This dissertation aims to advance both the technical development and application of PAT towards its clinical translation.

The first part of this dissertation describes the development of photoacoustic …

Developing Photoacoustic Tomography Devices For Translational Medicine And Basic Science Research, Tsz Wai Wong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) provides volumetric images of biological tissue with scalable spatial resolutions and imaging depths, while preserving the same imaging contrast—optical absorption. Taking the advantage of its 100% sensitivity to optical absorption, PAT has been widely applied in structural, functional, and molecular imaging, with both endogenous and exogenous contrasts, at superior depths than pure optical methods. Intuitively, hemoglobin has been the most commonly studied biomolecule in PAT due to its strong absorption in the visible wavelength regime.

One of the main focuses of this dissertation is to investigate an underexplored wavelength regime—ultraviolet (UV), which allows us to image …

Transcriptional Regulation Of Arrhythmia: From Mouse To Human, Yun Qiao

McKelvey School of Engineering Graduate Student Theses & Dissertations

In the last two decades, our understanding of cardiac arrhythmias has been accelerated immensely by the development of genetically engineered animals. Transgenic and knockout mice have been the “gold standard” platforms for delineating disease mechanisms. Much of our understanding of the pathogenesis of atrial and ventricular arrhythmias is gained from mouse models that alter the expression of specific ion channels or other proteins. However, cardiac arrhythmias such as atrial fibrillation are heterogeneous diseases with numerous distinct conditions that could not be explained exclusively by the disruption of ionic currents. Increasing evidence suggests disruption of signaling pathways in the pathogenesis of …

The Role Of Obesity And Dietary Fatty Acid Content In Regulating Humeral Bone And Cartilage Homeostasis, Lauren Votava

McKelvey School of Engineering Graduate Student Theses & Dissertations

Objective: The goal of this study was to investigate the effects of different dietary fatty acids in the context of diet-induced obesity on bone and cartilage in the humerus. It is known that obesity increases the severity of injury-induced osteoarthritis in the knee, however it is not fully understood what pathological changes have occurred due to diet alone¹. Additionally, while it is known that shoulder osteoarthritis has a link to obesity, the alterations in this joint are incompletely described.

Methods: In order to examine diet-induced changes in both bone and cartilage, this research utilized mice that had been …

Ls301 Fluorescence-Guided Photodynamic Therapy Of Brain Cancer Using Ppix Photosensitizer, Haini Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Incomplete brain tumor removal always causes neurologic deficit, disease recurrence and high mortality. Protoporphyrin IX (PpIX) accumulated in glioma cells with exogenous 5-aminolevulinic acid (5-ALA) serves as contrast agent for fluorescence-guided surgery and as well as acts as a photosensitizer for photodynamic therapy (PDT). However, the accurate tumor delineation using PpIX is limited by autofluorescence and superficial penetration depth. LS301 is a tumor-targeted near-infrared (NIR) contrast agent developed in our lab which allows deeper tumor imaging and avoids autofluorescence. My project aims to investigate whether LS301 can improve PpIX mediated PDT and tumor removal surgery. We have demonstrated co-localization of …

System Characterizations And Optimized Reconstruction Methods For Novel X-Ray Imaging, Huifeng Guan

McKelvey School of Engineering Graduate Student Theses & Dissertations

In the past decade there have been many new emerging X-ray based imaging technologies developed for different diagnostic purposes or imaging tasks. However, there exist one or more specific problems that prevent them from being effectively or efficiently employed. In this dissertation, four different novel X-ray based imaging technologies are discussed, including propagation-based phase-contrast (PB-XPC) tomosynthesis, differential X-ray phase-contrast tomography (D-XPCT), projection-based dual-energy computed radiography (DECR), and tetrahedron beam computed tomography (TBCT). System characteristics are analyzed or optimized reconstruction methods are proposed for these imaging modalities. In the first part, we investigated the unique properties of propagation-based phase-contrast imaging technique …

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Graduate Student Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

Characterizing Anisotropy In Fibrous Soft Materials By Mr Elastography Of Slow And Fast Shear Waves, John Larson Schmidt

McKelvey School of Engineering Graduate Student Theses & Dissertations

The general objective of this work was to develop experimental methods based on magnetic resonance elastography (MRE) to characterize fibrous soft materials. Mathematical models of tissue biomechanics capable of predicting injury, such as traumatic brain injury (TBI), are of great interest and potential. However, the accuracy of predictions from such models depends on accuracy of the underlying material parameters. This dissertation describes work toward three aims. First, experimental methods were designed to characterize fibrous materials based on a transversely isotropic material model. Second, these methods are applied to characterize the anisotropic properties of white matter brain tissue ex vivo. Third, …

Characterization Of Structural Dynamics Of The Human Head Using Magnetic Resonance Elastography, Andrew Arun Badachhape

McKelvey School of Engineering Graduate Student Theses & Dissertations

In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing in vivo estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims …

Comparison Of The Bi-Directional Performance Of Micro-Channel Sieve And Thin-Film Time Peripheral Nerve Interfaces, Robert Coker

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sophisticated motorized prosthetic limbs contain multiple degrees of freedom of motion as well as embedded pressure and angle transducers to provide sensory feedback in amputees. Although several central neural recording and stimulation modalities exist for both controlling these motions and providing sensory feedback from a prosthetic limb, directly interfacing the peripheral nerves which originally innervated the limb has many advantages. A difficulty with this bi-directional approach is that electrically stimulating axons to provide haptic feedback creates stimulation artifacts at neighboring recording sites within the nerve that are several orders of magnitude larger than the electroneurogram used for control. In this …

Functional Bio-Nano Hybrids Through A Precise Control Of Interfacial Interactions At The Nanoscale, Sirimuvva Tadepalli

McKelvey School of Engineering Graduate Student Theses & Dissertations

During the course of evolution, proteins have evolved to perform exquisite functions including structural support, signal transduction, actuation, sensing, catalysis, trafficking, gating, light-harvesting, charge transfer, molecular recognition, self-assembly, self-organization, or combinations of two or more of these functions. A precise control and manipulation of the structure and function of proteins is conceivable with the advent of nanotechnology, which has facilitated the integration of nanomaterials with functional biomolecules to realize bio-nano hybrids with synergistically enhanced functionalities.

At the genesis of bionanotechnology, a paucity in the fundamental understanding of the bio-nano interfaces is a grave impediment to the progress of the field. …

Bio-Inspired Multi-Spectral And Polarization Imaging Sensors For Image-Guided Surgery, Nimrod Missael Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Image-guided surgery (IGS) can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky, costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities to distinguish cancerous from healthy tissue. In my thesis, I have addressed these challenges in IGC by mimicking the visual systems of several animals to construct low power, compact and highly sensitive multi-spectral and color-polarization sensors. I …

Image Reconstruction Of The Speed Of Sound And Initial Pressure Distributions In Ultrasound Computed Tomography And Photoacoustic Computed Tomography, Thomas Paul Matthews

McKelvey School of Engineering Graduate Student Theses & Dissertations

Ultrasound computed tomography (USCT) and photoacoustic computed tomography (PACT) are two emerging imaging modalities that have a wide range of potential applications from pre-clinical small animal imaging to cancer screening in human subjects. USCT is typically employed to measure acoustic contrasts, including the speed of sound (SOS) distribution, while PACT typically measures optical contrasts or some related quantity such as the initial pressure distribution. Their complementary contrasts and similar implementations make USCT and PACT a natural fit for a hybrid imaging system. Still, much work remains to realize this promise. First, USCT image reconstruction methods based on the acoustic wave …

Reconstruction Algorithms For Novel Joint Imaging Techniques In Pet, Homayoon Ranjbar

McKelvey School of Engineering Graduate Student Theses & Dissertations

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types.

The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as ¹¹C, ¹³N, and ¹⁸F, can be used to label molecules, and tracers, such …

System Optimization And Iterative Image Reconstruction In Photoacoustic Computed Tomography For Breast Imaging, Yang Lou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic computed tomography(PACT), also known as optoacoustic tomography (OAT), is an emerging imaging technique that has developed rapidly in recent years. The combination of the high optical contrast and the high acoustic resolution of this hybrid imaging technique makes it a promising candidate for human breast imaging, where conventional imaging techniques including X-ray mammography, B-mode ultrasound, and MRI suffer from low contrast, low specificity for certain breast types, and additional risks related to ionizing radiation. Though significant works have been done to push the frontier of PACT breast imaging, it is still challenging to successfully build a PACT breast imaging …

Development Of In Vitro Drug Screening Platforms Using Human Induced Pluripotent Stem Cell-Derived Cardiovascular Cells, Yosuke Kurokawa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Drug-induced cardiotoxicity is a critical challenge in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes (CMs), researchers have explored ways to utilize these cells for in vitro preclinical drug screening applications. One area of interest is microphysiological systems (i.e. organ-on-a-chip), which aims to create more complex in vitro models of human organ systems, thus improving drug response predictions. In this dissertation, we investigated novel analysis methods and model platforms for detecting drug-induced cardiotoxicity using human induced pluripotent stem cell (iPSC)-derived cardiovascular cells.

First, we utilized human iPSC-derived CMs (iPS-CMs) to establish optical methods of …

Development And Validation For A Mobile Speech-In-Noise Audiometric Task, Tommy Peng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Traditional speech-in-noise hearing tests are performed by clinicians with specialized equipment. Furthermore, these tasks often present contextually weak sentences in background babble, which are poor representations of real-world situations. This study proposes a mobile audiometric task, Semantic Auditory Search, which uses the Android platform to bypass the need for specialized equipment and presents multiple tasks of two competing real-world conversations to estimate the user’s speech-in-noise hearing ability. Through linear regression models built from data of seventy-nine subjects, three Semantic Auditory Search metrics have been shown to have statistically significant (p < 0.05) with medium effects sizes for predicting QuickSIN SNR50. The internal consistency of the task was also high, with a Cronbach’s alpha of 0.88 or more across multiple metrics. In conclusion, this preliminary study suggests that Semantic Auditory Search can accurately and reliably perform as an automated speech-in-noise hearing test. It also has tremendous potential for extension into automated tests of cognitive function, as well.

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Photodynamic Therapy: Agents And Mechanisms, Rebecca Claire Gilson

McKelvey School of Engineering Graduate Student Theses & Dissertations

Despite enormous efforts, cancer remains a leading cause of morbidity and mortality world-wide. The main challenges currently facing cancer therapy include lack of adequate tumor targeting, failure to treat hypoxic tumor cells, and induction therapy resistant tumors. A solution to these limitations can be found in photodynamic therapy (PDT) which combines light and light activatable compounds, photosensitizers (PSs), to produce cytotoxic reactive oxygen species (ROS) to damage tumor tissue. This creates a spatiotemporal therapeutic effect, where cell damage only occurs at the intersection of the PS and light. PDT can treat tumors through unique mechanisms which reduce induction of tumor …

Intrinsic And Extrinsic Biomechanical Factors In A Co-Adaptive Ecog-Based Brain Computer Interface, Jonathan Carl Landes

McKelvey School of Engineering Graduate Student Theses & Dissertations

Paralysis, due to spinal cord injury, amyotrophic lateral sclerosis (ALS), or stroke, is the result of severed communication between the brain and the motor periphery. Brain computer interfaces (BCIs) are neuroprosthetic devices that create novel communication pathways by measuring and transforming neural activity into operational commands. State of the art BCI systems measure brain activity using penetrating electrode arrays able to record from hundreds of individual cortical neurons simultaneously. Unfortunately, these systems are highly susceptible to signal degradation which limits their efficacy to 1-2 years. However, electrocorticography (ECoG) signals recorded from the surface of the brain deliver a more competitive …

Designing Metabolite Biosensors And Engineering Genetic Circuits To Regulate Metabolic Pathways, Di Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbial production of chemicals has provided an attractive alternative to chemical synthesis. A key to make this technology economically viable is to improve titers, productivities, and strain robustness. However, pathway productivities and yields are often limited by metabolic imbalances that inhibit cell growth and chemical production. In contrast, natural metabolic pathways are dynamically regulated according to cellular metabolic status. Dynamic regulation allows cells to adjust metabolite concentrations to optimal levels and avoid wasting carbon and energy. Inspired by nature, synthetic regulatory circuits have shown great promise in improving titers and productivities, because they can balance the metabolism by dynamically adjusting …