Biomedical Engineering and Bioengineering Commons^™

Computational Fluid Dynamics Modeling Of Hemodialysis In Patients With An Arteriovenous Fistula, Maximilian Roth

McKelvey School of Engineering Graduate Student Theses & Dissertations

With the advent of arteriovenous fistula (AVF) for use in hemodialysis, the anastomosis built for such use has become a central point of the study to understand the flow and wall shear stresses in such a system since very large wall shear stresses can lead to arterial/vein rupture. Considering the commonly used creation site of an anastomosis as connecting the radial artery to the cephalic vein, a model is created to calculate the wall shear stresses across various components of the system. The model depicts a connection of the specified vein and artery bridged together allowing the increase in blood …

Development Of Optical Coherence Tomography Angiography System For Mouse Eye Imaging And Measurement Of Vasodilation, Yilin Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical coherence tomography angiography (OCTA) is broadly known as a non-invasive technology that allows examining the retinal and choroidal vasculatures, alternative to fluorescein angiography. In this study, we have developed an optical coherence tomography (OCT) system for imaging the mouse eye. We measure the retinal thickness, which is 216.53um. We apply OCTA to characterize the quantitative change in vessel diameter and the perfusion density of the retina after the wild-type mice are administered the adenosine or inhale carbon dioxide. Comparing the images acquired one minute and 5 minutes after the injection or CO₂ inhalation with the baseline, distinct changes …

Role Of Ligand Architecture On Collective Cell Invasion, Amrit Bagchi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Epithelial cell collectives utilize extra-cellular matrix (ECM) fibers to undergo collective migration critical in regeneration, repair and cancer metastasis. However, very little is known about the various factors which determine the ability of cellular collectives to utilize ECM fibers to undergo these critical processes in-vivo. First part of the dissertation focusses on understanding how cell collectives exploit specific properties, like stiffness and fiber length to undergo collective streaming. It is also unclear how cellular forces, cell-cell adhesion, and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of …

Fast And Radiation-Free High-Resolution Mr Cranial Bone Imaging For Pediatric Patients, Parna Eshraghi Boroojeni

McKelvey School of Engineering Graduate Student Theses & Dissertations

AbstractEach year, 2.2 million pediatric head computed tomography (CT) scans are performed in the United States. Head trauma and craniosynostosis are two of the most common pediatric conditions requiring head CT scans. Head trauma is common in children and one-third of the patients that present to the emergency room undergoes head CT imaging. Craniosynostosis is a congenital disability defined by a prematurely fused cranial suture. Standard clinical care for pediatric patients with head trauma or craniosynostosis uses high-resolution head CT to identify cranial fractures or cranial sutures. Unfortunately, the ionizing radiation of CT imaging imposes a risk to patients, particularly …

Understanding Control Of Metabolite Dynamics And Heterogeneity, Christopher John Hartline

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes live in complex and continually changing environments. Rapid shifts in nutrient availability are a common challenge for microbes, and cause changes in intracellular metabolite levels. Microbial response to dynamic environments requires coordination of multiple levels of cellular machinery including gene expression and metabolite concentrations. This coordination is achieved through metabolic control systems, which sense metabolite concentrations and direct cellular activity in response. Several reoccurring control architectures are found throughout diverse metabolic systems, which suggests underlying evolutionary advantages for using these control systems to coordinate metabolism. One common, yet understudied, control architecture is the positive feedback metabolite uptake loop, which …

Plasmonic Nanomaterials-Based Point-Of-Care Biosensors, Rohit Gupta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Point-of-care (POC) biosensors, although rapid and easy-to-use, are orders magnitude less sensitive than laboratory-based tests. Further they are plagued by poor stability of recognition element thus limiting its widespread applicability in resource-limited settings. Therefore, there is a critical need for realizing stable POC biosensors with sensitivity comparable to gold-standard laboratory-based tests. This challenge constitutes the fundamental basis of this dissertation work– to expand access to quality and accurate biodiagnostic tools. At the heart of these solutions lies plasmonic nanoparticles which exhibit unique optical properties which are attractive for label-free and labelled biosensors.Firstly, we improve the stability and applicability of label-free …

Modeling The Effects Of Mechanical Loading On Hypertrophic Cardiomyopathy Pathogenesis In Human Induced Pluripotent Stem Cell Derived Micro Heart Muscle, Jingxuan Guo

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sudden cardiac death in the young is devastating. Advances in genetics have associated mutations in the contractile sarcomere apparatus of cardiomyocytes with hypertrophic cardiomyopathy, the most frequent cause of sudden cardiac death in the young. Currently, it is challenging to predict genotype-phenotype relationships in hypertrophic cardiomyopathy due to its incomplete disease penetrance. For example, different patients from the same family with identical genomic variants develop different symptoms. Non-genetic, environmental factors such as blood pressure are critical in heart function and disease. Therefore, understanding how mechanical factors contribute to phenotypes in diseases like hypertrophic cardiomyopathy is critical for developing effective therapeutics. …

Machine Learning And Scalable Informatics Methods To Predict Disease Status From Multimodal Biomedical Data, Hossein Mohammadian Foroushani

McKelvey School of Engineering Graduate Student Theses & Dissertations

Biological understanding of complex diseases such as stroke and obesity is critical for the advancement of medicine. Further knowledge discovery can provide effective biomarkers to improve disease diagnosis and prognosis, identify driver mutations, predict individual genetic susceptibility for early prevention and effective disease management, and facilitate development of personalized drugs. Stroke is the second leading cause of death and long-term disability in the world. Thus, stroke management is a time-sensitive emergency. The initial hours after stroke onset map the trajectory of subsequent neurologic complications. Cerebral edema develops hours to days after acute ischemic stroke and may result in midline shift …

Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros

McKelvey School of Engineering Graduate Student Theses & Dissertations

Proton radiotherapy has the potential to treat tumors with better conformal dose distribution than competing modalities when the rapid dose falloff at the end of the proton-beam range is correctly aligned to the edge of the clinical target volume (CTV). However, its clinical potential is dependent on the accurate localization of the Bragg-peak position from predicted stopping-power ratio maps. The method that is most commonly used in today’s clinical practice for predicting stopping-power ratio (SPR) consists of a stoichiometric calibrationtechnique based on single-energy CT (SECT) for direct estimation of patient-specific SPR distribution from vendor-reconstructed Hounsfield Unit (HU) images. Unfortunately, this …

Ligand- And Strain-Specific Control Of Microbial Communities, Austin Grant Rottinghaus

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microbes naturally coexist in complex, multi-strain communities that are valuable assets for their host. Commensal and probiotic microbes prevent pathogen colonization, reduce the frequency and severity of various ailments, provide essential nutrients, and offer various additional benefits. Understanding the dynamics of and tailoring microbial communities to provide additional beneficial functions is a primary focus of researchers in medicine and agriculture. To date, consortia have primarily been manipulated by supplementing the communities with microbes that were engineered in vitro or by introducing stimuli that alter the metabolism or composition of the community. This method has proven successful, with numerous microbes engineered …

Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Neuromodulation technology is key to understanding brain function and treating brain diseases. Conventional neuromodulation technologies, such as direct current stimulation, transcranial magnetic stimulation, and optogenetics, predominately rely on electromagnetic waves. However, the fundamental physical law  the tradeoff-relationship between penetration and spatial resolution, limits their transcranial penetration within the superficial cortex layer. To overcome this challenge, electrodes or optical fibers need to be surgically implanted into the brain to modulate specific brain regions. Different from electromagnetic waves, ultrasound, as a mechanical wave, can non-invasively penetrate through the intact skull to reach deep brain regions with millimeter spatial focus. Ultrasound has …

Pet/Mr Imaging Biomarkers For Cerebral Small Vascular Diseases: Tissue Oxygenation Stress And Neuroinflammation, Chunwei Ying

McKelvey School of Engineering Graduate Student Theses & Dissertations

Fifty million people are affected by dementia worldwide. Cerebral small vessel disease (CSVD) often leads to vascular contributions to cognitive impairment and dementia (VCID), the second leading cause of dementia after Alzheimer’s disease (AD), accounting for up to 45% of dementia. White matter hyperintensities (WMH) on fluid-attenuated inversion recovery (FLAIR) imaging and disrupted white matter microstructure on diffusion tensor imaging (DTI) have been widely used as biomarkers to evaluate CSVD.

The pathogenesis underlying CSVD is not well understood. It has been postulated that exposure to risk factors, including hypertension, diabetes, and smoking over years injures small arterioles, impairs autoregulation and …

Development Of The Assessment Of Clinical Prediction Model Transportability (Apt) Checklist, Sean Chonghwan Yu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Clinical Prediction Models (CPM) have long been used for Clinical Decision Support (CDS) initially based on simple clinical scoring systems, and increasingly based on complex machine learning models relying on large-scale Electronic Health Record (EHR) data. External implementation – or the application of CPMs on sites where it was not originally developed – is valuable as it reduces the need for redundant de novo CPM development, enables CPM usage by low resource organizations, facilitates external validation studies, and encourages collaborative development of CPMs. Further, adoption of externally developed CPMs has been facilitated by ongoing interoperability efforts in standards, policy, and …

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …

Focused Ultrasound-Enabled Blood-Based Liquid Biopsy (Sonobiopsy) For Brain Disease Diagnosis, Christopher Pham Pacia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Brain cancer severely threatens human health due to its disruption of neurological function, poor prognosis, and substantial reduction in quality of life. Glioblastoma (GBM) is the most devastating brain cancer; not only is it the most common malignant primary tumor in adults, but also it has a median survival of 14 months with a 5-year survival rate of less than 5%. Despite advances in multidisciplinary treatment that includes surgical resection, radiation therapy, and chemotherapy, almost all patients experience tumor progression and nearly universal mortality within 2 years. However, advances in patient care have suggested that the accurate diagnosis of molecular …

Advancing The Portability, Field Of View, And Spatiotemporal Resolution Of Multi-Parametric Photoacoustic Microscopy, Fenghe Zhong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Capable of structural, functional, molecular, and metabolic imaging with high spatial resolution in vivo, photoacoustic microscopy (PAM) is an emerging tool in biomedical research. Further, recent advances in multi-parametric acquisition and analysis make PAM uniquely capable of simultaneously mapping the total concentration of hemoglobin (CHb), oxygen saturation of hemoglobin (sO2), and blood flow speed. However, there are multiple major limitations, including, the large footprint, low imaging speed, limited imaging contrast, and insufficient axial resolution, which impedance its applications in basic and translational research. In this dissertation, I presented potential solutions to overcome the limitations above.In the first part of this …

Intrinsic Cardiac Effects Of Severe Acute Respiratory Syndrome Coronavirus 2 In Coronavirus Disease 2019, Brittany Danielle Brumback

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiac arrhythmias, particularly ventricular arrhythmias, can be life-threatening and caused by both congenital genetic mutations and acquired cardiac injury. My thesis work was originally focused on delineating the effects of genetic mutation-driven dysregulation of a protein called Hey2 in Brugada Syndrome, a complex disease characterized by a predisposition to dangerous arrhythmias originating in the right ventricular outflow tract. In response to the pandemic, my thesis work shifted toward understanding the mechanisms of cardiovascular injury in Coronavirus disease 2019 (COVID-19), which is associated with serious cardiovascular complications, including ventricular arrhythmias and sudden cardiac death as well as endothelial dysfunction and coagulopathies. …

Imaging Techniques For Proton Range Determination In Proton Therapy, Xinyuan Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Proton therapy can achieve better sparing of normal tissues than the conventional photon radiation therapy due to proton’s Bragg Peak property. However, to unlock the full potential of protons, accurate prediction of in vivo proton stopping power ratio (SPR) is required for proton therapy treatment planning. The current standard practice is to map SPR from Hounsfield Unit (HU) values of a single-energy computed tomography (SECT) scan through a stoichiometric calibration technique. This technique is subjected to a variety of factors that congregate on the uncertainties in SPR estimation, including the calibration uncertainty (up to 0.5% to 1.8% of the total …

Measuring G Protein Activation With Spectrally Resolved Fluorescence Fluctuation Spectroscopy, Daniel Foust

McKelvey School of Engineering Graduate Student Theses & Dissertations

Fluorescence fluctuation spectroscopy (FFS) is comprised of a set of statistical techniques used to learn information about fluorescence particles by analyzing intensity fluctuations in signals detected from a fluorescence spectrometer or microscope. In biological contexts, FFS is commonly used to quantify the concentrations, molecular brightnesses, and transport properties (e.g. diffusion coefficients) of labeled biomolecules. In particular, the molecular brightness parameter is valuable because it can be used to quantify oligomerization of biomolecules. Therefore, FFS has emerged as an attractive tool for measuring protein-protein interactions in live cells. This dissertation describes the development of image-based, multicolor FFS techniques. Image-based FFS is …

Active Testing Of Executive Functions: Toward More Efficient And Equitable Individual Behavioral Modeling, Mariluz Rojo Domingo

McKelvey School of Engineering Graduate Student Theses & Dissertations

Inferences about executive functions are commonly drawn through serial administration of various individual assessments that often take a long time to complete and cannot capture complex trends across multiple variables. In an attempt to improve upon current methods used to estimate latent brain constructs, this thesis makes two primary contributions to the field of behavioral modeling. First, it brings attention to sequential designs for more efficient diagnostic testing of fluctuations in executive functions with respect to a baseline level. It was shown that a sequential framework was successfully capable of detecting significant differences in cognitive performance more rapidly than conventional …

Application Of Neural Networks To Predict Patient-Specific Cellular Parameters In Computational Cardiac Models, Chang Hi Lee

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sudden cardiac death(SCD) is a significant cause of death that accounts for more than 180,000 deaths in the US and 4 million deaths worldwide annually. SCDs are mainly caused by irregular heartbeats called arrhythmias, which are caused by abnormal electrical activity within the heart. Precision medicine, in the form of personalized computational cardiac models of a patient’s heart, can suggest optimal therapies for cardiac arrhythmias. Prior work has used finite element meshes derived from cardiac MRIs to simulate cardiac electrical activity. In this study, I sought to augment this approach by developing a neural network to learn the parameters that …

Resolving The Three-Dimensional Rotational And Translational Dynamics Of Single Molecules Using Radially And Azimuthally Polarized Fluorescence, Oumeng Zhang, Weiyan Zhou, Jin Lu, Tingting Wu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We report a radially and azimuthally polarized (raPol) microscope for high detection and estimation performance in single-molecule orientation-localization microscopy (SMOLM). With 5000 photons detected from Nile red (NR) transiently bound within supported lipid bilayers (SLBs), raPol SMOLM achieves 2.9 nm localization precision, 1.5° orientation precision, and 0.17 sr precision in estimating rotational wobble. Within DPPC SLBs, SMOLM imaging reveals the existence of randomly oriented binding pockets that prevent NR from freely exploring all orientations. Treating the SLBs with cholesterol-loaded methyl-β-cyclodextrin (MβCD-chol) causes NR’s orientational diffusion to be dramatically reduced, but curiously NR’s median lateral displacements drastically increase from 20.8 to …

Plasmonically-Enhanced Dna-Rna Hybrid-Based Bioassay For Amplification-Free Quantification Of Sars-Cov-2, Yuxiong Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Corona Virus Disease 2019 (COIVD-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious respiratory illness. Within just a few months, it spread around the whole world and became a global pandemic. Real-time reverse-transcription polymerase chain reaction (RT-PCR) works as a gold standard method diagnosing COVID-19 with high sensitivity and specificity. But due to the programs of RT-PCR, it usually takes more than 24 hours to get the results while specialized devices are also required. False-negative results can happen as well using RT-PCR which increase the risk of spreading coronavirus. To promote quicker detection of COVID-19, …

Toward Lignin Valorization: Development Of Rhodococcus Opacus Pd630 As A Chassis For Triacylglycerol (Tag) Production From Recalcitrant Aromatic Feedstocks, Rhiannon R. Carr

McKelvey School of Engineering Graduate Student Theses & Dissertations

The advent of the industrial era was precipitated by the discovery of fossil fuels, and ushered in unprecedented changes for humanity included but not limited to the development of rapid transit and communications, improvements to food distribution and preservation, the mass production of goods, and a radical rearrangement of communities from relatively small enclaves to metropolises. With all the benefits, however, come considerable costs, especially to the global environment. Greenhouse gas emissions, built up over centuries of unregulated combustion, have precipitated a rate of global temperature change unparalleled in the 4.5 billion-year history of this planet. In order to preserve …

Single-Molecule Localization Microscopy Of 3d Orientation And Anisotropic Wobble Using A Polarized Vortex Point Spread Function, Tianben Ding, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Within condensed matter, single fluorophores are sensitive probes of their chemical environments, but it is difficult to use their limited photon budget to image precisely their positions, 3D orientations, and rotational diffusion simultaneously. We demonstrate the polarized vortex point spread function (PSF) for measuring these parameters, including characterizing the anisotropy of a molecule’s wobble, simultaneously from a single image. Even when imaging dim emitters (∼500 photons detected), the polarized vortex PSF can obtain 12 nm localization precision, 4°–8° orientation precision, and 26° wobble precision. We use the vortex PSF to measure the emission anisotropy of fluorescent beads, the wobble dynamics …

Using Computer Vision To Track Anatomical Structures During Cochlear Implant Surgery, Nicholas Bach

McKelvey School of Engineering Graduate Student Theses & Dissertations

There is a steep learning curve for surgeons performing cochlear implant surgeries. We aimed to use computer vision to track anatomical features with the goal of helping surgeons perform cochlear implant surgery without damaging the cochlea. We compared nine algorithms in total, seven object tracking algorithms and two optical flow algorithms utilizing the LucasKanade method, on manually created cochlear implant surgery videos to determine the accuracy associated with each. Compared with eight other algorithms, we observed that an iterative pyramidal implementation of the Lucas-Kanade (IPLK) method, implemented through OpenCV, performed the best. The IPLK method had the lowest error rate …

Photoacoustic Imaging, Feature Extraction, And Machine Learning Implementation For Ovarian And Colorectal Cancer Diagnosis, Eghbal Amidi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Among all cancers related to women’s reproductive systems, ovarian cancer has the highest mortality rate. Pelvic examination, transvaginal ultrasound (TVUS), and blood testing for cancer antigen 125 (CA-125), are the conventional screening tools for ovarian cancer, but they offer very low specificity. Other tools, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), also have limitations in detecting small lesions. In the USA, considering men and women separately, colorectal cancer is the third most common cause of death related to cancer; for men and women combined, it is the second leading cause of cancer deaths. …

Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris

McKelvey School of Engineering Graduate Student Theses & Dissertations

The cellular mechanisms for loading-induced bone formation, from osteocyte mechano-sensation to osteoblast-directed bone formation, are not well understood. Elucidating these mechanisms and identifying any processes that are disrupted in aged mice can aide in the development of new anabolic drugs for treating diseases like osteoporosis. This thesis begins by investigating the genes expressed by osteocytes following loading at an early mechanosensitive (4-hr) timepoint, and later at a bone-forming (day 5) timepoint. We demonstrated increases in Ngf and Wnt1 in osteocyte-enriched intracortical bone by laser capture microdissection and microarray analysis. These results were important in demonstrating the presence of Ngf in …

Attachment Of Fibrous Materials In Nature And Surgical Repair, Ethan Daniel Hoppe

McKelvey School of Engineering Graduate Student Theses & Dissertations

Mother nature is the ultimate problem solver. Often by brute force and necessity for survival, the organism that has the best solution to a problem is the one to proliferate. One of these problems for which nature provides an elegant solution is the attachment of dissimilar materials. This dissertation explores the strengthening and relaxation of interactions between soft and hard materials, typically with one of the two being fibrous in character, with the goal of identifying strategies for improving the surgical reattachment of tendon to bone. The work begins with a study of the plant Harpagonella palmeri, which the dissertation …

Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cartilage is essential to joint development and function. However, there is a variety of cartilage diseases, ranging from developmental (e.g., skeletal dysplasias) to degenerative (e.g., arthritis), in which treatments and therapeutics are lacking. For example, specific point mutations in the ion channel transient receptor potential vanilloid 4 (TRPV4) prevent proper joint development, leading to mild brachyolmia and severe, neonatally lethal metatropic dysplasia. Tissue-engineered cartilage offers an opportunity to elucidate the underlying mechanisms of these cartilage diseases for the development of treatments. Human induced pluripotent stem cells (hiPSCs) are an improved cell source option for cartilage tissue engineering given their minimal …