Biomedical Engineering and Bioengineering Commons^™

Evaluating Neuroimaging Modalities In The A/T/N Framework: Single And Combined Fdg-Pet And T1-Weighted Mri For Alzheimer’S Diagnosis, Peiwang Liu

McKelvey School of Engineering Theses & Dissertations

With the escalating prevalence of dementia, particularly Alzheimer's Disease (AD), the need for early and precise diagnostic techniques is rising. This study delves into the comparative efficacy of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and T1-weighted Magnetic Resonance Imaging (MRI) in diagnosing AD, where the integration of multimodal models is becoming a trend. Leveraging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we employed linear Support Vector Machines (SVM) to assess the diagnostic potential of these modalities, both individually and in combination, within the AD continuum. Our analysis, under the A/T/N framework's 'N' category, reveals that FDG-PET consistently outperforms T1w-MRI across …

Integrating Implantable Bci Devices Within Bci2000 Using A Unified Framework And Toolchain For In-Vivo Research, Dhruva Mehta

McKelvey School of Engineering Theses & Dissertations

The field of neurotechnology research has a bright and promising future as more devices are created. However, there are still many gaps in the field as the potential for neuromodulation grows. Devices such as the Micro-Leads StimZ system and the Ripple Grapevine/Summit system help bridge that gap by allowing for a broader variety of closed-loop neuromodulation experiments to be implemented thanks to their portability and versatility. Despite these devices being on the market, however, there needs to be a method to collaborate and interact with them across multiple research institutions. BCI2000 helps to address that by creating a standardized working …

Investigating Murine Uterine Tissue Dynamics: Biomechanical And Histological Perspectives On Postpartum Involution And Scar-Induced Remodeling, Savannah Elizabeth Chatman

McKelvey School of Engineering Theses & Dissertations

During pregnancy, the uterus undergoes structural and mechanical transformations to withstand the demands of a successful delivery. In cases where vaginal birth is not feasible, a Cesarean section (c-section), which involves a transverse abdominal incision, is used to facilitate delivery of the fetus and placenta¹. Following the procedure, the uterus and abdominal tissue are carefully sutured to support postpartum recovery, leading to uterine scarring at the incision site^1,2. Understanding the relationship between uterine scar integrity, postpartum involution, and the biomechanics of uterine tissue is a crucial step toward predicting the risk of uterine rupture during future …

The Role Of Voluntary Descending Control In Enhancing Motor Function Via Transcutaneous Spinal Cord Stimulation, Yoon Kim

McKelvey School of Engineering Theses & Dissertations

Spinal cord injury (SCI) is a life-changing event that causes lasting motor impairments. Transcutaneous spinal cord stimulation (tSCS), a non-invasive form of neuromodulation in which electrodes are placed on the skin and used to stimulate the spinal circuits via an electrical current, has demonstrated positive effects on motor function recovery in individuals who have had SCIs. However, the precise mechanism of how tSCS interacts with voluntary descending drive remains poorly understood. This study aims to investigate the role of voluntary descending control in influencing reflex responses triggered by tSCS.

Electromyography (EMG) recordings were performed in ten unimpaired individuals while they …

Development Of A Wearable Short-Wave Infrared Photoplethysmography Device For Detection And Monitoring Of Hemodilution During Postpartum Hemorrhage, Hannah Gruensfelder

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS

A Thesis on the Development of a Wearable Short-Wave Infrared Photoplethysmography Device for Detection and Monitoring of Hemodilution During Postpartum Hemorrhage

by

Hannah Gruensfelder

Master of Science in Biomedical Engineering

Washington University in St. Louis, 2024

Professor Christine O’Brien, Chair

Postpartum hemorrhage (PPH), the leading cause of maternal death and morbidity, affects nearly 14 million people worldwide each year, disproportionally impacting racial minorities and people in low resource settings. A timely diagnosis of PPH is key in providing optimal patient care, as an estimated 90% of deaths due to PPH are preventable with early diagnosis and …

Environment And Response Of 3d-Encapsulated Mesenchymal Stem Cells To Mechanical Loading, Augustus Greenwood

McKelvey School of Engineering Theses & Dissertations

This thesis explores the micromechanical environment induced when cyclically compressing hydrogels via finite element modeling and experimentally on the impact of loading on mesenchymal stem cells (MSCs) when encapsulated withing 3D hydrogel matrices. Degenerative joint diseases, characterized by cartilage degradation, present significant challenges due to cartilage's limited self-repair capacity. Innovative approaches, including stem cell-based therapies and engineered biomaterials, have emerged as promising strategies for cartilage repair and regeneration. This work specifically investigates the calibration of a bioreactor, the uniformity of load response across the hydrogel constructs via finite element modeling (FEM), and the stress response of MSCs subjected to various …

Modeling Of Nk Cells In Pediatric Patients With Unusually Severe Or Recurrent Hsv Using High-Dimensional Flow Cytometry, Yunran Feng

McKelvey School of Engineering Theses & Dissertations

HSV infection is broadly spread all over the world with some patients having severe and/or recurrent HSV infections. Our lab studies human Natural Killer (NK) cells, which are important in innate immune responses to viral infections and tumors. A publication in 2013 by Ornstein et al from our lab studied HSV+ pediatric patients and found some associations between severe infection and defects in NK cytolytic function. PLCG2 haploinsufficient variants found in 2 HSV patients causing PLCγ2 hypophosphorylation, and loss of cytolytic function in NK cells is a novel finding recently published by Alinger et al from our lab in 2023. …

Low Impedance, Durable, Self-Adhesive Hydrogel Epidermal Electrodes For Electrophysiology Recording, Naiyan Wu

McKelvey School of Engineering Theses & Dissertations

Traditional electrodes used for electrophysiology recording, characterized by their hard, dry, and inanimate nature, are fundamentally mismatched with the soft, moist, and bioactive characteristics of biological tissues, leading to suboptimal skin-electrode interfaces. Hydrogel materials, mirroring the high water content and biocompatibility of biological tissues, emerge as promising candidates for epidermal electronic materials due to their adjustable physicochemical properties. However, challenges such as inadequate electrical conductivity, elevated skin impedance, unreliable adhesion in moist conditions, and performance decline from dehydration have significantly restricted the efficacy and applicability of hydrogel-based electrodes. In this thesis, we report a high-performance hydrogel epidermal electrode patch for …

6d Single-Fluorogen Orientation-Localization Microscopy For Elucidating The Architecture Of Beta-Sheet Assemblies And Biomolecular Condensates, Tingting Wu, Weiyan Zhou, Jai S. Rudra, Rohit V. Pappu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We develop six-dimensional single-molecule orientation-localization microscopy (SMOLM) to measure the 3D positions and 3D orientations simultaneously of single fluorophores. We show how careful optimization of phase and polarization modulation components can encode phase, polarization, and angular spectrum information from each fluorescence photon into a microscope’s dipole-spread function. We used the transient binding and blinking of Nile red (NR) to characterize the helical structure of fibrils formed by designed amphipathic peptides, KFE8^L and KFE8^D, and the pathological amyloid-beta peptide Aβ42. We also deployed merocyanine 540 to uncover the interfacial architectures of biomolecular condensates.

Design Of Human Serum Albumin And Adenovirus Conjugation Via Catcher/Tag Molecular Glue, Peijie Zhao

McKelvey School of Engineering Theses & Dissertations

Adenovirus (Ad) has been the ideal cargo delivery mechanism, and its moderate immunological response makes it ideal for in vivo gene therapies since its discovery in 1953. However, the robust immunogenicity of the Ad capsid and low vaccine absorption via mucous membranes and epithelium put a limit on the process of developing intranasal vaccines. Efforts are being made to enhance the effectiveness of Ad vectors and numerous studies have demonstrated the remarkable capacity of human serum albumin (HSA) to extend plasma half-life and facilitate targeted intranasal delivery. In this study, we devised an innovative method for employing the Catcher/Tag molecular …

Improving And Integrating Quantitative Single Cell Spatial Biology For Theranostic Medicine, Peng Lu

McKelvey School of Engineering Theses & Dissertations

Disease states are the result of a complex interplay of many different cell types interacting in close proximity in the context of often heterogeneous tissues. Alpha particles are drawing intense research and clinical interest because of their potent cytotoxic effects and their short path lengths. Analyzing the dose distribution and tissue micro-environment for alpha therapy plays a key role in predicting the efficacy of this targeted radiotherapy. However, to date there have been no direct on-tissue analytical methods for alpha dose distributions and the corresponding tissue microenvironments.

Therefore, we have developed a pipeline to overcome this limitation by utilizing quantitative …

Automatic Cardiac Mri Image Segmentation And Mesh Generation, Ziyuan Li

McKelvey School of Engineering Theses & Dissertations

Segmenting and reconstructing cardiac anatomical structures from magnetic resonance (MR) images is essential for the quantitative measurement and automatic diagnosis of cardiovascular diseases [1]. However, manual evaluation of the time-series cardiac MRI (CMRI) obtained during routine clinical care are laborious, inefficient, and tends to produce biased and non-reproducible results [2]. This thesis proposes an end-to-end pipeline for automatically segmenting short-axis (SAX) CMRI images and generating high-quality 2D and 3D meshes suitable for finite element analysis. The main advantage of our approach is that it can not only work as a stand-alone pipeline for the automatic CMR image segmentation and mesh …

Calculating The Difference In Stiffness Of Living T Cells Through Micropipette Aspiration, Minju Lee

McKelvey School of Engineering Theses & Dissertations

Cardiovascular disease (CVD) accounted for 17.9 million deaths in 2019, with fibrosis contributing to nearly a quarter of these fatalities [1,2]. Fibrosis, characterized by excessive connective tissue formation, has been strongly linked to T cells, essential components of the immune system. This study explores the mechanisms of T cell activation and the subsequent changes in biophysical properties like diameter, stiffness, and elasticity, aiming to develop therapeutic strategies for fibrosis-related diseases, including CVD. Utilizing the micropipette aspiration technique, we accurately assessed T cell stiffness and observed a change in bulk cell stiffness upon activation. The results demonstrated increased fluid-like behavior in …

The Effect Of Spinal Cord Stimulation And Video Games Training On Body-Machine Interface Control, Jie Fei

McKelvey School of Engineering Theses & Dissertations

Damage to the spinal cord causes long-lasting loss of motor and sensory function, and currently, there is no ‘cure’ for paralysis. However, even people with severe spinal cord injuries (SCI) have some residual mobility. Studies have shown that transcutaneous electrical spinal cord stimulation (tSCS) combined with functional training targeting residual mobility can further improve the motor function of individuals with SCI. In this study, we present a technical framework that aims to enhance rehabilitation outcomes by targeting residual mobility through a motor training-based approach. Our technical framework centers around a non-invasive body-machine interface (BoMI) that relies on the use of …

Novel Microfluidic Devices To Model The Interactions Between Lymphatics And Breast Cancer, Jade Weber

McKelvey School of Engineering Theses & Dissertations

The lymphatic system is responsible for immune circulation and fluid balance in the body. It accomplishes this by draining interstitial fluid from local tissue and transferring it to lymph nodes and back into blood circulation. However, this process is implicated in many pathologies, one of the most dangerous being breast cancer metastasis to the lymph nodes. The largest factor in breast cancer patient mortality is metastasis. Lymphangiogenesis, the growth of new lymphatic vessels, has been thought to play a dynamic role in aiding breast cancer metastasis. Breast cancer tumor cells have been shown to remodel the functionality of local lymph …

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …

A General-Purpose Software Platform For Closed-Loop Neuromodulation, William Engelhardt

McKelvey School of Engineering Theses & Dissertations

Implementing closed-loop neuromodulation therapies is a challenging and expensive endeavor. It requires developing software capable of acquiring signals from a bio-signal amplifier, analysis of these signals, and initiation of precisely timed stimulation, all of which need to be accomplished in real-time with very low latency. Developing this software is difficult, as it requires a wide range of expertise ranging from interfacing with hardware to real-time signal processing. Even when successfully implementing such a system for one set of hardware, it often then only works within the laboratory that conceived it. This is because of the inherent heterogeneity in the devices …

Dual Color Optogenetic Control For Analyzing Cardiac Function In Drosophila, Jiantao Zhu

McKelvey School of Engineering Theses & Dissertations

Prolonged consumption of carbohydrate-rich diets and immobile lifestyles frequently cause metabolic disorders and obesity and, as a result, may lead to progressive heart dysfunction among broad social groups of the population. Drosophila melanogaster serves as an essential model organism in cardiovascular disease research due to conserved physiological and genomic traits shared with humans, its genetic and molecular toolbox versatility, and cost-effective maintenance. Here, we combine optogenetics and optical coherence tomography to study cardiovascular function in D. melanogaster. A new optogenetic pacing system has been developed, employing a transgenic line carrying two opsins: ChR2 and NpHR2.0. A custom-built hardware setup …

A Novel Mrna Delivery Strategy Employing Adenovirus Piggyback Mrna Binders Via Catcher/Tag Molecular Glue, Kexin Geng

McKelvey School of Engineering Theses & Dissertations

mRNA-based therapeutics open a new era for the prevention and treatment of a wide range of diseases. However, existing mRNA delivery vehicles have limited repertoires for dendritic cell targeting and intranasal administration which are two paramount delivery pathways of significant advantages for treating cancer and infectious respiratory diseases. Adenovirus (Ad) with well-deciphered viral genomes and intensive-studied structure biology has been developed for DCs-targeted cancer vaccines and intranasal COVID vaccines. In light of these virtues, Ad presents as the “off-the-shelf” tool possessing well-defined manufacturable capabilities and translatable feasibility that perfectly complements the current limitations of mRNA delivery. In this study, we …

3-Dimensional Visualization Of Cardiac Plaque Mapping Data, Phan Ly Vy Nguyen

McKelvey School of Engineering Theses & Dissertations

Atrial Fibrillation (AF) of one of the most prevalent cardiac arrythmia in humans, and also the most studied arrythmias due to its high association with cardiovascular morbidity and mortality. Diagnosis of AF, which is highly dependent on the observation of the irregular signal in the atria, is often challenging since AF is often asymptomatic at the onset. There has been a lot of effort in exploring different cardiac mapping techniques to understand the dynamics of AF for better intervention. This study aims at developing a MATLAB interface that assists the development of a cardiac plaque mapping data acquisition system in …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Single-Molecule Super-Resolution Imaging Of Geobacter Sulfurreducens Under Anaerobic Conditions, Ziyi Hu

McKelvey School of Engineering Theses & Dissertations

Geobacter sulfurreducens are anaerobic bacteria capable of making electrical contacts with other organisms and extracellular electron acceptors. The challenge of imaging live Geobacter bacteria is maintaining anaerobic conditions during the imaging process. In this thesis, we augment a single-molecule localization microscope (SMLM) with a home-built anaerobic imaging chamber and use constant argon bubbling to maintain oxygen-free imaging conditions. To validate the imaging protocol, we use the transient binding of Nile red to resolve the spherical morphology of lipid-coated glass spheres with nanoscale resolution. However, when imaging Geobacter, the distribution of Nile red localizations is non-uniform, both between different cells …

Development Of Methods To Enhance Stem Cell Derived Islet Survival, Aining Fan

McKelvey School of Engineering Theses & Dissertations

No abstract provided.

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park

McKelvey School of Engineering Theses & Dissertations

Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …

Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi

Arts & Sciences Electronic Theses and Dissertations

Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …

Six-Dimensional Single-Molecule Imaging With Isotropic Resolution Using A Multi-View Reflector Microscope, Oumeng Zhang, Zijian Guo, Yuanyuan He, Tingting Wu, Michael D. Vahey, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Imaging of both the positions and orientations of single fluorophores, termed single-molecule orientation-localization microscopy, is a powerful tool for the study of biochemical processes. However, the limited photon budget associated with single-molecule fluorescence makes high-dimensional imaging with isotropic, nanoscale spatial resolution a formidable challenge. Here we realize a radially and azimuthally polarized multi-view reflector (raMVR) microscope for the imaging of the three-dimensional (3D) positions and 3D orientations of single molecules, with precisions of 10.9 nm and 2.0° over a 1.5-μm depth range. The raMVR microscope achieves 6D super-resolution imaging of Nile red molecules transiently bound to lipid-coated spheres, accurately resolving …

Dei Without Equity: Lab Coat Culture And Persistent Racism In Bioengineering Laboratories, Janet Canady

Arts & Sciences Electronic Theses and Dissertations

From biased algorithms to discriminatory devices to medical racism, it is clear that biomedical products are created in ways that reproduce racial disparities in access and use. Yet the most common solutions recommended by biomedical research institutions emphasize diversity, equity, and inclusion practices that research has already proven ineffective and sometimes harmful. In fact, labs rarely scrutinize whether and how their research products reflect racial bias, assumptions, or ideals. In this paper, I shift the focus to consider how bioengineering laboratories function as a site in which racial processes contribute to product outcomes. I ask, what are the racial dynamics …

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

McKelvey School of Engineering 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 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 …