Biomedical Engineering and Bioengineering Commons^™

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 …

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 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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 …

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

McKelvey School of Engineering 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. …

Assessment And Diagnosis Of Human Colorectal And Ovarian Cancer Using Optical Imaging And Computer-Aided Diagnosis, Yifeng Zeng

McKelvey School of Engineering Theses & Dissertations

Tissue optical scattering has recently emerged as an important diagnosis parameter associated with early tumor development and progression. To characterize the differences between benign and malignant colorectal tissues, we have created an automated optical scattering coefficient mapping algorithm using an optical coherence tomography (OCT) system. A novel feature called the angular spectrum index quantifies the scattering coefficient distribution. In addition to scattering, subsurface morphological changes are also associated with the development of colorectal cancer. We have observed a specific mucosa structure indicating normal human colorectal tissue, and have developed a real-time pattern recognition neural network to localize this specific structure …

Deep Learning For Task-Based Image Quality Assessment In Medical Imaging, Weimin Zhou

McKelvey School of Engineering Theses & Dissertations

It has been advocated to use objective measures of image quality (IQ) for assessing and optimizing medical imaging systems. Objective measures of IQ quantify the performance of an observer at a specific diagnostic task. Binary signal detection tasks and joint signal detection and localization (detection-localization) tasks are commonly considered in medical imaging. When optimizing imaging systems for binary signal detection tasks, the performance of the Bayesian Ideal Observer (IO) has been advocated for use as a figure-of-merit (FOM). The IO maximizes the observer performance that is summarized by the receiver operating characteristic (ROC) curve. When signal detection-localization tasks are considered, …

Exploring Attacks And Defenses In Additive Manufacturing Processes: Implications In Cyber-Physical Security, Nicholas Deily

McKelvey School of Engineering Theses & Dissertations

Many industries are rapidly adopting additive manufacturing (AM) because of the added versatility this technology offers over traditional manufacturing techniques. But with AM, there comes a unique set of security challenges that must be addressed. In particular, the issue of part verification is critically important given the growing reliance of safety-critical systems on 3D printed parts. In this thesis, the current state of part verification technologies will be examined in the con- text of AM-specific geometric-modification attacks, and an automated tool for 3D printed part verification will be presented. This work will cover: 1) the impacts of malicious attacks on …

Development Of High-Speed Photoacoustic Imaging Technology And Its Applications In Biomedical Research, Yun He

McKelvey School of Engineering Theses & Dissertations

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

McKelvey School of Engineering Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on …

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

McKelvey School of Engineering Theses & Dissertations

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

In …

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

McKelvey School of Engineering Theses & Dissertations

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

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

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

McKelvey School of Engineering Theses & Dissertations

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

However, due to physiological motion, scattering of light …

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

McKelvey School of Engineering Theses & Dissertations

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

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 …

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 …

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 …