Biomedical Engineering and Bioengineering Commons^™

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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. …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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, …

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

McKelvey School of Engineering 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 …

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 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 And Validation For A Mobile Speech-In-Noise Audiometric Task, Tommy Peng

McKelvey School of Engineering 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.

Development Of High Resolution Tools For Investigating Cardiac Arrhythmia Dynamics, Christopher Reed Gloschat

McKelvey School of Engineering Theses & Dissertations

Every year 300,000 Americans die due to sudden cardiac death. There are many pathologies, acquired and genetic, that can lead to sudden cardiac death. Regardless of the underlying pathology, death is frequently the result of ventricular tachycardia and/or fibrillation (VT/VF). Despite decades of research, the mechanisms of ventricular arrhythmia initiation and maintenance are still incompletely understood.

A contributing factor to this lack of understanding is the limitations of the investigative tools used to study VT/VF. Arrhythmias are organ level phenomena that are governed by cellular interactions and as such, near cellular levels of resolution are needed to tease out their …

Improving Pure-Tone Audiometry Using Probabilistic Machine Learning Classification, Xinyu Song

McKelvey School of Engineering Theses & Dissertations

Hearing loss is a critical public health concern, affecting hundreds millions of people worldwide and dramatically impacting quality of life for affected individuals. While treatment techniques have evolved in recent years, methods for assessing hearing ability have remained relatively unchanged for decades. The standard clinical procedure is the modified Hughson-Westlake procedure, an adaptive pure-tone detection task that is typically performed manually by audiologists, costing millions of collective hours annually among healthcare professionals. In addition to the high burden of labor, the technique provides limited detail about an individual’s hearing ability, estimating only detection thresholds at a handful of pre-defined pure-tone …

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

McKelvey School of Engineering 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 …

Mechanobiology Of Epithelial Clusters In Ecms Of Diverse Mechanical Properties, Samila Nasrollahi

McKelvey School of Engineering Theses & Dissertations

Cell clusters reside in complex extracellular matrices (ECMs) of varying mechanical properties. Epithelial cells sense and translate the mechanical cues presented by the surrounding ECM into biochemical signals through a process called ‘mechanotransduction’, which controls fundamental aspects of disease and development. During the course of metastasis, mechanical changes in the tumor microenvironment can lead to declustering of epithelial cells through a process called epithelial-to-mesenchymal transition (EMT). Throughout different steps of metastasis, escaped epithelial clusters encounter heterogeneous tissues of varying mechanical properties that ultimately influence their behavior in distant locations within the body. This dissertation investigates the mechanobiology of epithelial clusters …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering 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 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 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 …

Composition-Dependent Mechanisms Of Multiscale Tendon Mechanics, Fei Fang

McKelvey School of Engineering Theses & Dissertations

Tendons serve as an integral part of the musculoskeletal system by transferring loads from muscle to bone and providing joint mobility and stability. From the physiologically-loading perspective, while progress has been made in evaluating mechanical behavior of different types of tendons in tension, further work is needed to relate tendon mechanics to compositional and microstructural properties, particularly under non-tensile loading modalities (i.e., shear, compression). This information is vital to explore mechanisms of how mechanical signals lead to changes in tendon structure and composition to enable these tissues to function properly, including in in vivo multiaxial loading conditions. From the structural …

Characterization Of The High Frequency Alternating Current Block In The Rat Sciatic Nerve Using Cuff Electrodes And Macro-Sieve Electrodes, Soumyajit Ray

McKelvey School of Engineering Theses & Dissertations

Tripolar cuff electrodes were designed, fabricated and non-chronically implanted in the sciatic nerve of two-month-old Lewis rats. A proximal constant current stimulus to the nerve was blocked by applying a high frequency sinusoidal signal to the distally placed tripolar cuff electrode. The frequency voltage characteristic of the blocking signal was obtained. Complete block was not achieved using variants of the tripolar cuff design and bipolar cuff electrodes. Single and dual macro-sieve electrode assemblies were designed, fabricated and chronically implanted in the sciatic nerve of Lewis rats. After a four-month period for regeneration four different electrode configurations were tested to enable …

The Impact Of The Mitochondrial Metabolism Of Induced Pluripotent Stem Cells Upon Differentiation, Stefanie T. Shahan

McKelvey School of Engineering Theses & Dissertations

Induced pluripotent stem cells (iPSCs) can be differentiated into any cell type found in the body. The derivation of a stem cell derived β cell (SC-β) capable of responding to glucose by secreting insulin was hugely significant for diabetes research and opened up the possibility of cell replacement therapy to combat this widespread disease (Pagliuca et al. 2014). The optimization of differentiation procedures such as this could improve yield, function, cost, and efficiency of a stem cell-derived product. Current approaches to improve differentiation are primarily focused on signal transduction pathways, while the metabolic state of the cells has received little …

Assessing Dprestin & Nadc1 (Indy) Interaction On Calcium Oxalate Crystal Formation In A Drosophila Model Of Kidney Stones, Jessica Lin

Undergraduate Research Symposium Posters

Calcium oxalate (CaOx) accounts for >70%of kidney stones, yet why CaOx stones form is poorly understood. While several factors contribute to the stone aggregation and growth, elucidating the roles of oxalate transporters can help demystify this phenomenon. Using a Drosophila model to study the formation and inhibition of CaOx crystals in the fly Malpighian tubule (MT), oxalate transport via dPrestin—the fly Slc26a6 Cl^-/Ox^2- exchanger was studied using both electrophysiology and MT dissection with CaOx birefringence assays. Here, the fly model suffices as it recapitulates renal oxalate excretion. Additionally, the mammalian dicarboxylate transporter NaDC1 (Indy in Drosophila) …