Bioimaging and Biomedical Optics Commons^™

Utilizing Spatial Transcriptomics To Compare Gene Expression In Volumetric Muscle Loss Injury Recovery, Colton Gattis

Biomedical Engineering Undergraduate Honors Theses

Volumetric Muscle Loss (VML) injuries are known to disrupt the normal regenerative process via fibrosis leading to an extensive permanent loss of muscle function. The specific causation of this disruption remains to be defined; however, with new developments in transcriptomics, genetic trends can be identified across regions of tissue over time. This study follows VML injuries within the tibialis anterior of a mouse model for fifteen days after initial injury to attempt to identify expected transitions in healing. Genetic presence began to become more diversified as recovery progressed from four to fifteen days post injury with spatial clusters becoming globalized …

Autofluorescence Imaging Of Endogenous Metabolic Cofactors In Response To Cytokine Stimulation Of Classically Activated Macrophages, Shelby N. Bess, Matthew J. Igoe, Abby C. Denison, Timothy J. Muldoon

Biomedical Engineering Faculty Publications and Presentations

Background

Macrophages are one of the most prevalent subsets of immune cells within the tumor microenvironment and perform a range of functions depending on the cytokines and chemokines released by surrounding cells and tissues. Recent research has revealed that macrophages can exhibit a spectrum of phenotypes, making them highly plastic due to their ability to alter their physiology in response to environmental cues. Recent advances in examining heterogeneous macrophage populations include optical metabolic imaging, such as fluorescence lifetime imaging (FLIM), and multiphoton microscopy. However, the method of detection for these systems is reliant upon the coenzymes NAD(P)H and FAD, which …

Correlation Of Intracellular Metabolites With Optical Metabolic Imaging In Polarized Macrophages As Indicators Of Metabolic Reprogramming, Abby Claire Denison, Shelby Bess

Biomedical Engineering Undergraduate Honors Theses

Macrophages are a type of immune cell that are characterized by their ability to differentiate into various active phenotypes based on environmental stimuli. They can generally be classified as one of two extremes: inflammatory/M1 or wound-healing/M2. Macrophage populations in vivo, however, are rarely homogenous, and since macrophages play vital roles in the immune response, particularly in the context of the tumor microenvironment (TME), it’s important to be able to investigate and understand heterogenous macrophage populations to develop more effective treatments. Recently, autofluorescence imaging such as multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactors NADH and FAD have …

A Comparison Of Optical Measurement Methods For The Growth Of S. Cerevisiae, Jackson Black

Chemical Engineering Undergraduate Honors Theses

Genetic engineering of living organisms provides the opportunity to express and harvest different proteins from cell surfaces. Yeast (S. cerevisiae) is one such organism and is capable of being grown on an industrial scale. Cellular concentration is an important parameter to monitor while fermentation processes are underway, in order to control the environment inside the growth medium and maximize yields. Spectrophotometry is a conventional method for measuring concentration, but is limited by a narrow absorbance range, and the need for on-site periodic sampling. A continuous method of measurement, as provided by Bug Labs BE2100 non-invasive biomass monitor, would …

Automated Segmentation Of Autofluorescence Lifetime Images Using A Convolutional Neural Network, Nicole Hooten

Biomedical Engineering Undergraduate Honors Theses

Chronic wounds affect nearly 1 out of every 50 people in the United States, decreasing quality of life and putting people with potential comorbidities at high risk for obtaining an infection. Wound healing progress in clinical settings is measured by tracking wound size and there are currently no non-invasive, quantitative measurement techniques. Previous studies have proposed nicotinamide adenine dinucleotide (NADH) autofluorescence lifetime (FLIM) imaging of the wound edge as a method to quantify the wound healing process by connecting the role of NADH in cellular metabolism to wound healing stage. However, evaluation of FLIM images is heavily subjective, as a …

Surface Laser Texturing Of Cocrmo Alloys, Gabriel Dharwadker

Biomedical Engineering Undergraduate Honors Theses

Artificial orthopedic implants such as hip joints suffer from excessive wear due to excess friction between the polyethylene and cobalt-chromium-molybdenum surfaces of the device. This increase in friction causes a fraction of them to give out within ten years. Therefore, to minimize the probability of this happening, recent research has been conducted regarding laser surface texturing of the cobalt-chromium-molybdenum alloy components of artificial joints. These surface textures serve to mimic the native lubrication mechanisms of cartilage in natural joints, which, in a natural joint, lowers the friction. However, the production of these laser surface textures is still a field of …

Assessing The Potential Effectiveness Of Diffuse Reflectance Spectroscopy For Quantifying Neonatal Skin Properties Using Tissue Phantoms, Jack Murphy

Biomedical Engineering Undergraduate Honors Theses

Diffuse reflectance spectroscopy (DRS) has previously been shown to be effective at analyzing the optical characteristics of a wide variety of biological tissues, including the skin. In addition to being sensitive to the amount of blood and its oxygenation, DRS can be used to extract bilirubin levels and assess jaundice, a common complication in newborn infants. To assess its potential for being utilized in applications involving neonatal skin, we evaluated the utility of DRS for extracting hemoglobin and bilirubin concentrations from tissue phantoms. Phantom sets were created by including a known amount of scattering and by varying known concentrations of …

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

The Effects Of Microgravity On Human Endothelial Cells In Relation To Deep Vein Thrombosis, Allie Burgess

Biomedical Engineering Undergraduate Honors Theses

Deep vein thrombosis (DVT) is a condition where blood clots form in one or more of the deep veins of the body, causing leg pain and/or swelling, potentially leading to pulmonary embolism and/or stroke. The incidence of DVT among astronauts serving on the International Space Station has been shown to be greater than that of the general population, calling into question the effects of microgravity on human thrombolytic processes. Additionally, microgravity conditions have been shown to cause muscular atrophy and a decrease in muscle strength and mobility. Because collagen composes a large portion of muscle tissue, this study also assessed …

Determination Of Tissue-Level Changes In Tumors That Are Indicative Of Metastasis Using Optical Spectroscopy, Sanidhya D. Tripathi

Biomedical Engineering Undergraduate Honors Theses

Breast cancer, accounting for 12% of all new cancer cases, is one of the leading causes of death in women worldwide. Although patient survival has improved over the years, metastatic spread to other organ sites and not due to the primary tumor is the most common form of tumor recurrence, accounting for 90% deaths. Hypoxia is a common hallmark of solid tumors and is linked with metastasis, therapeutic resistance, and poor patient survival. Defined as a state of decreased oxygen availability, cells under hypoxia have an increased rate of genetic mutation, local invasion, and resistance to treatment such as radiation …

3d Volumetric Mapping Of Tissue Properties Via A Catheter-Scale Microendoscope Imaging System, Andrew Stark

Biomedical Engineering Undergraduate Honors Theses

The study of tumor microvasculature is an important area of interest for research and clinical communities; however, there are significant limitations in the clinical characterization of the tumor microenvironment. Optical methods offer quantitative real-time measurement of tissue structure and perfusion and can be miniaturized for deployment endoscopically into previously inaccessible locations. However, conventional optical methods (i.e., optical coherence tomography, white light endoscopy, etc.) gives limited information about tissue perfusion while the diameter of various optical probes along with the complexity of scanning mechanisms make it difficult to access certain areas. In this study, a new technique for characterizing the tumor …

Investigating The Impact Of Hypoxia On Reactive Oxygen Species Generation Within Murine Breast Cancer Cells, Jared Mcpeake

Biomedical Engineering Undergraduate Honors Theses

When cancer metastasizes from a primary tumor site to secondary site through the bloodstream or lymph, the cancer becomes more difficult to treat. For this reason, it is vital to study what indicates the metastatic potential of a tumor. Current research has shown that cell lines with high metastatic potential display increased levels of metabolic adaptability over their nonmetastatic counterparts after undergoing hypoxic conditions. One method of assessing this adaptability is to measure the concentration of reactive oxygen species (ROS) produced by the cells while undergoing oxidative stress. In highly adaptable metastatic cells, an increase of ROS buildup within the …

Erythrocyte Deformability In Response To Glucose Using Liquid Crystals, Jayden Goff

Biomedical Engineering Undergraduate Honors Theses

The worldwide prevalence of diabetes mellitus is rapidly increasing with about 9.3% of the adult population living with the disease. People with diabetes have trouble regulating their blood glucose levels which typically leads to hyperglycemia. Under normal physiological conditions, erythrocytes can undergo deformations in response to shear stress when passing through capillaries with a smaller diameter. Poorly managed hyperglycemia can lead to the glycosylation of erythrocyte membrane proteins and hemoglobin. This glycosylation leads to increased rigidity of the cells along with decreased deformability in response to mechanical stress; therefore, these cells have a higher susceptibility of getting stuck in the …

Clot Analogs For The Development Of Improved Treatment Methods In Ischemic Stroke, Charles A. Rieth

Biomedical Engineering Undergraduate Honors Theses

According to the CDC, nearly 800,000 individuals experience stroke each year in the United States [1]. Greater than 70% of strokes are of ischemic etiology and involve the occlusion of key arteries in the cardiovascular system [2]. Tissue plasminogen activator (IV-tPA) is the current gold standard for thrombolytic approaches [3]; however, this therapeutic is only effective between 3 and 4.5 hours from the patient’s last know well [4]. As a result, less than 5% of acute ischemic stroke patients receive IV-tPA. In order to increase the viability of AIS treatment as a whole, it is essential that thrombolytic techniques are …

The Influence Of Mmp14 On Angiogenesis In Chemotherapy-Treated Tumors, Abdussaboor Muhammad

Biomedical Engineering Undergraduate Honors Theses

Colorectal cancer is the third most common cancer in the world, and it is the fourth most common cause of cancer related death (1). There have been many significant advancements regarding the treatment of cancer which aim to shrink the size of tumors in patients. However, there is still more that needs to be understood about the many different factors that play a role in colorectal cancer development.

Angiogenesis is the process of forming new blood vessels from existing ones and it requires breaking down and remodeling of the extracellular matrix (ECM) in order to allow endothelial cells to migrate …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

In Vitro Mitral Valve Model With Unrestricted Ventricular Access: Using Vacuum To Close The Valve And Enable Static Trans-Mitral Pressure, Sam E. Stephens, Alexander J. Kammien, Jacob C. Paris, Alexis P. Applequist, Neil B. Ingels, Hanna K. Jensen, Drew E. Rodgers, Charles R. Cole, Jonathan F. Wenk, Morten O. Jensen

Biomedical Engineering Faculty Publications and Presentations

Current in vitro models of the left heart establish the pressure difference required to close the mitral valve by sealing and pressurizing the ventricular side of the valve, limiting important access to the subvalvular apparatus. This paper describes and evaluates a system that establishes physiological pressure differences across the valve using vacuum on the atrial side. The subvalvular apparatus is open to atmospheric pressure and accessible by tools and sensors, establishing a novel technique for experimentation on atrioventricular valves. Porcine mitral valves were excised and closed by vacuum within the atrial chamber. Images were used to document and analyze closure …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

Metabolic Profiling Of Radiation Resistance In Head And Neck Squamous Cell Carcinoma, Natalie Curry

Biomedical Engineering Undergraduate Honors Theses

Abstract

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide. Radiation therapy is one of the most common treatments for HNSCC, however, many patients do not respond to radiation therapy. Currently, it takes about a month for clinicians to definitively determine whether a tumor is responsive to radiation therapy. Current studies have identified that the prevention of mitochondrial oxidative stress caused by reactive oxygen species can prevent DNA damage and lead to a decrease in apoptosis in radiation resistant cells Measuring the oxygen consumption rate through Seahorse metabolic assays allows us to quantify basal respiration, maximal …

Using Deep Learning To Analyze Materials In Medical Images, Carson Molder

Computer Science and Computer Engineering Undergraduate Honors Theses

Modern deep learning architectures have become increasingly popular in medicine, especially for analyzing medical images. In some medical applications, deep learning image analysis models have been more accurate at predicting medical conditions than experts. Deep learning has also been effective for material analysis on photographs. We aim to leverage deep learning to perform material analysis on medical images. Because material datasets for medicine are scarce, we first introduce a texture dataset generation algorithm that automatically samples desired textures from annotated or unannotated medical images. Second, we use a novel Siamese neural network called D-CNN to predict patch similarity and build …

Quantifying Blood Flow Patterns In The Pediatric Heart Using Blood Speckle Imaging, Harrison Dean

Biomedical Engineering Undergraduate Honors Theses

Congenital Heart Disease (CHD) is the most common type of congenital disease worldwide. Echocardiography using Doppler ultrasound is typically used to diagnose and monitor CHD; however, it is angle-dependent in nature and as a result is limited in its ability to accurately evaluate ventricular function. Blood Speckle Imaging (BSI) is a novel, angle-independent imaging modality that provides detailed blood flow information and visualization within a given area using speckle-tracking. In this study, velocity-field information obtained from BSI was used to calculate flow parameters such as kinetic energy (KE) and circulation using a custom created MATLAB program. BSI was performed on …

Quantifying Mucosal Hemodynamics In A Murine Model Of Ulcerative Colitis With Diffuse Reflectance Spectroscopy, Elizabeth A. Bullard, Ariel I. Mundo, Shelby N. Bess, Kathryn P. Miller

Biomedical Engineering Undergraduate Honors Theses

Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence 10 out of every 100,000 people in North America and Western Europe. Though the exact etiology is uncertain, a number of studies have shown that inflammatory cells along with environmental factors, genetics, and lifestyle habits can contribute to the sustained inflammatory response. In order to determine the cellular mechanism behind relapse and remission of UC, researchers have frequently employed immunohistochemistry, western blotting and gene sequencing, but these destructive analysis methods require the removal of a sample, necessarily limiting these methods to …

Quantification Of Superoxide Production In Cells Treated With L-Buthionine Sulfoximine, Rebekah Townsley

Biomedical Engineering Undergraduate Honors Theses

Hydroxyl radicals, superoxides, and hydrogen peroxides are common reactive oxygen species (ROS) that are produced by the mitochondria during cellular respiration [1]. Signal transduction pathways in the mitochondria are used to maintain the balance of ROS. However, when these mechanisms fail to regulate ROS properly, it causes oxidative damage and can lead to the development of various diseases such as cancer, respiratory, neurodegenerative, and cardiovascular diseases. L-buthionine sulfoximine (BSO) has been used previously to induce oxidative stress by inhibiting the γ-GCS enzyme used to synthesize glutathione, an antioxidant used to convert ROS to water [3]. BSO reduces glutathione production, thus …

Monitoring Fgf1-Treated Skin Wounds With Label-Free Multiphoton Microscopy, Gianna Busch

Biomedical Engineering Undergraduate Honors Theses

Chronic skin wounds pose a significant threat to public health, affecting as many as 5.5 million people in the United States every year and costing the healthcare system $10 billion annually^1,2. These wounds are associated with prolonged inflammation, poor vascularization, increased infection risk, and high mortality rates^3,4. There is significant interest in developing and testing a variety of biologics to promote wound healing. However, quantitative evaluations of healing are typically limited to measurements of wound size, and there is a critical need to develop quantitative biomarkers sensitive to different aspects of the healing process. Label-free multiphoton …

Developing Aligned Nerve Scaffolds In A 3d Type-I Collagen Gel, Gabriel David

Biomedical Engineering Undergraduate Honors Theses

Despite significant progress in the field of peripheral nerve repair, clinical success is still limited, leaving millions to suffer from peripheral neuropathy with billions spent every year for treatment. Nerve repair methods that are capable of maximizing the regenerative properties of peripheral nerves are greatly desired in the field of medical science. This research aims to fill the gap between modern methods and the future of nerve repair by creating type-I collagen scaffolds with aligned degradation pores that will assist and nurture nerves growing through them. This is achieved by incorporating adipose stem cells into type-I collagen hydrogels and aligning …

Statistical Machine Learning For Breast Cancer Detection With Terahertz Imaging, Tanny Andrea Chavez Esparza

Graduate Theses and Dissertations

Breast conserving surgery (BCS) is a common breast cancer treatment option, in which the cancerous tissue is excised while leaving most of the healthy breast tissue intact. The lack of in-situ margin evaluation unfortunately results in a re-excision rate of 20-30% for this type of procedure. This study aims to design statistical and machine learning segmentation algorithms for the detection of breast cancer in BCS by using terahertz (THz) imaging. Given the material characterization properties of the non-ionizing radiation in the THz range, we intend to employ the responses from the THz system to identify healthy and cancerous breast tissue …

Understanding Radiation Resistance In Head And Neck Tumor Xenografts Using Diffuse Reflectance And Raman Spectroscopy, Sina Dadgar

Graduate Theses and Dissertations

Each year, 800,000 new patients are diagnosed with head and neck squamous cell carcinoma (HNSCC), a majority of whom are treated with a combination of daily fractions of radiation and weekly chemotherapy sessions for up to seven weeks. Current methods to evaluate treatment response of individual patients are limited to anatomical measurements of tumor burden using CT scan or MRI 4-8 weeks after completion of treatment. However, earlier knowledge of radiation-response prior to or at early days after commencement of therapy can aid oncologist with escalating and de-escalating treatment plans for exceptionally non-responding and responding patients. Such a knowledge can …

Multiphoton Microscopy And Deep Learning Neural Networks For The Automated Quantification Of In Vivo, Label-Free Optical Biomarkers Of Skin Wound Healing, Jake D. Jones

Graduate Theses and Dissertations

Non-healing ulcerative wounds that occur frequently in diseases such as diabetes are challenging to diagnose and treat due to numerous possible etiologies and the variable efficacy of wound care products. With advanced age, skin wound healing is often delayed, leaving elderly patients at high risk for developing these chronic injuries. As it is challenging to discriminate age-related delays from disease-related chronicity, there is a critical need to develop new quantitative biomarkers that are sensitive to wound status. Multiphoton microscopy (MPM) techniques are well-suited for 3D imaging of epithelia and are capable of non-invasively detecting metabolic cofactors (NADH and FAD) without …

Autofluorescence Spectral Unmixing For Quantitative Metabolic Imaging Within Tissues, Lucy Woodbury

Biomedical Engineering Undergraduate Honors Theses

Label-free metabolic imaging through quantification of NADH and FAD autofluorescence has become a powerful and efficient tool for non-invasive measurements of cell metabolism. It has applications in a variety of fields including diagnostic and therapeutic monitoring. However, NADH and FAD imaging typically selects specific single excitation and emission bands where it is assumed that these fluorophores are individually isolated. In some cases of isolated cell imaging, this assumption holds true, but for samples with other intrinsic fluorophores present (i.e. collagen and elastin), it can interfere with quantitative results. Elastin and collagen autofluorescence prevent the broader application of these optical metabolic …

The Utilization Of Autofluorescence To Study The Effects Of L-Buthionine-Sulfoximine On Cellular Metabolism In Vitro, Madison Belew

Biomedical Engineering Undergraduate Honors Theses

Oxidative damage and stress impacts metabolic activity and has been implicated in a number of diseases . These medical conditions have been found to be associated with a lack of glutathione (GSH). There is a need to study the effects that the absence of glutathione has in order to expand knowledge of indicators that cause conditions like cataracts, cancer, or impaired wound healing. L-buthionine-sulfoximine (BSO) has been used in past studies to hinder GSH production and induce oxidative stress within a cell. This study explores the effects of BSO and induced oxidative stress on the metabolic activity and processes within …