Bioimaging and Biomedical Optics Commons^™

A Functional Ultrasound Imaging (Fusi) Pipeline For Investigating Brain-Wide Hemodynamics During Torpor-Like Hypothermia, Owen J. Culver

McKelvey School of Engineering Graduate Student Theses & Dissertations

Torpor is a regulated state of reduced metabolic demand that enables animals to conserve energy under unfavorable environmental conditions. The controlled induction of a similar state, termed synthetic torpor, has potential applications in ischemic protection, organ preservation, cancer treatment, radiation protection, and long-term spaceflight. Although neuronal populations within the preoptic hypothalamus have been shown to initiate hypothermic and hypometabolic states, the distributed cerebral hemodynamic dynamics accompanying their induction and maintenance remain poorly understood. In this thesis, we developed an accessible functional ultrasound imaging (fUSI) acquisition and analysis pipeline and applied it to investigate cerebral hemodynamics during chemogenetic activation of the …

Development Of A Light-Based Platform To Assess Cervical Mucus Barrier Function And Physical Mucus Properties, Elizabeth J. Buzbee

McKelvey School of Engineering Graduate Student Theses & Dissertations

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide, yet current clinical tools for predicting its risk lack specificity and reliability. Cervical mucus plays a crucial role in maintaining pregnancy by forming a barrier that protects the uterus against infection. This study investigates the use of laser speckle rheology as a noninvasive technique to assess cervical mucus biomechanics. Synthetic cervical mucus was fabricated at varying hydration levels and tested using a conventional rheometer that confirmed that the mechanical properties of the synthetic mucus samples were representative of physiological cervical mucus. These results were compared to the complex …

Automated Beam Stitching And Segmentation Procedure For Space Division Multiplexing Optical Coherence Tomography Angiography, Andrew J. Song

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical Coherence Tomography Angiography (OCTA) has revolutionized ophthalmic imaging and its capability to produce high-resolution 3D maps of the retinal microvasculature is instrumental in diagnosing retinovascular diseases such as diabetic retinopathy and age-related macular degeneration; However, the existing OCTA devices often suffer from slow acquisition speed limiting the field-of-view (FOV) in the clinic. Space Division Multiplexing OCTA (SDM-OCTA) address these limitations by acquiring multiple beams simultaneously, achieving manyfold faster acquisition speeds than single beam OCTA systems. But as each beam contains only part of the image, SDM-OCTA requires additional processing steps to produce coherent wide-field images. Though manual stitching and …

Data-Driven Insights Into Spatial Patterns And Disease Etiologies Of White Matter Hyperintensities, Sugandha Roy

McKelvey School of Engineering Graduate Student Theses & Dissertations

In this thesis, we have applied Orthogonal Projective Non-Negative Matrix Factorization (opNMF) to identify spatial patterns of white matter hyperintensities (WMH) within UK Biobank's imaging data. Our selection criteria excluded subjects with a history of neurological, mental, and specific cerebrovascular conditions, allowing us to focus on WMH patterns in a healthy aging population. We have interrogated the association of location-specific WMHs with a variety of demographic, clinical, and genetic factors. Our multivariable regression analysis evaluates the strength and nature of the associations between these factors and WMH distribution. The analysis integrates variables such as age, sex, smoking habits, medication usage …

An Attention Lstm U-Net Model For Drosophila Melanogaster Heart Tube Segmentation, Xiangping Ouyang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Machine learning is commonly used in biomedical image analysis, as it allows automated image segmentation and identification that minimizes the need for tedious human involvement. Drosophila melanogaster is often used as a cardiac disease model, where optical coherence microscopy (OCM) is used to image and analyze its beating dynamics. As OCM often generates a large volume of images, automated image segmentation is necessary to quantify the heart beating efficiently. Our most recent heart segmentation model, FlyNet 2.0+, is a fully convolutional LSTM U-Net model. However, the performance of the model diminishes in the presence of artifacts, such as image reflection …

Calcium Analysis Of Intercellular Communications Between Alpha Cells And Delta Cells Across The Pancreatic Islet, Shichao Gao

McKelvey School of Engineering Graduate Student Theses & Dissertations

The intricate communication between different cell types within pancreatic islets plays a crucial role in regulating glucose homeostasis. Among these cellular interactions, the interplay between α cells (responsible for glucagon secretion) and δ cells (secreting somatostatin) is particularly intriguing due to the inhibitory effects of somatostatin on glucagon release. Understanding the intercellular interactions between α and δ cells may provide insights into the mechanisms underlying the coordinated regulation of blood glucose levels. In this study, we employed a multi-modal approach combining confocal imaging, image analysis, and correlation network analysis to investigate the spatial relationships and potential functional connections between α …

Structured Light Radial-View Endoscope Imaging Development For Evaluation Of Human Tissue, Xiyan Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

In this thesis, we improved an existing structured light methodology to more accurately estimate tissue optical properties imaged in a single snapshot. The developed approach is a major enhancement of the traditional three-phase spatial frequency domain imaging system: It greatly simplifies the operational procedure while also maintaining high accuracy in optical property measurements .

Leveraging this improved approach, we have developed a low-cost, compact, and radial-view endoscope prototype. This prototype combines affordability with high functionality and a user-friendly design. To assess the performance and reliability of our endoscope, we conducted comprehensive evaluations involving tissue-mimicking phantoms, as well as ex vivo …

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 Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

Development Of A Multispectral Vis-Swir Imaging Modality For Cutaneous Water Assessment, Quinlan Mcgrath

McKelvey School of Engineering Graduate Student Theses & Dissertations

Inflammatory skin diseases are estimated to impact 20% of the global population and are the fourth leading cause of nonfatal disability worldwide. Diagnosis and management are predominantly based on clinician visual assessment of disease related changes in skin morphology. The qualitative nature of this method can result in misdiagnosis and underdiagnoses of treatable diseases. There persists systematic undertreatment of skin of color patients given the more subtle presentation of erythema against pigmented skin. There exists a clinical need for a quantitative and objective inflammation assessment tool that meets the needs of a diverse patient population. The accumulation of interstitial fluid …

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

McKelvey School of Engineering Graduate Student 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 …

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 …

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 …

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 …

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 …

Injectable Ct/Mri Contrast Agent For Gastrointestinal Tumor Tracking, Luna Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Gastrointestinal cancers remain to be of the most common and deadly cancers worldwide. Early detection and treatments are crucial for reducing mortality and improving patient outcome. Radiation therapy is a non-invasive localized tumor treatment method, and utilizes radiation to kill the cancerous cells and shrink tumors at specific sites. Precise localization at the target tumor site is therefore important before radiation therapy, especially for gastrointestinal tumor sites located in the moving bowel. Currently, invasive endoscopies along with ink tattoos are used for identifying tumor location, which often require sedation and bring much discomfort. Imaging tests, including CT and MRI, play …

Focused Ultrasound-Mediated Drug Delivery To The Brainstem, Dezhuang Ye

McKelvey School of Engineering Graduate Student Theses & Dissertations

Brainstem gliomas are tumors that occur in the brainstem, the brain region that connects the brain to the spinal cord and controls vital body functions. The critical anatomic location of the brainstem precludes surgical intervention and limits the use of invasive therapeutic techniques. Moreover, the frequently intact blood-brain barrier (BBB) of most brainstem gliomas prevents therapeutic agents from reaching the diseased site. The currently available techniques for brain drug delivery are either invasive (e.g., convection-enhanced delivery) or lack targeting to the diseased site (e.g., intranasal brain drug delivery). Novel techniques that can noninvasively overcome the BBB are critically needed for …

Computational Imaging Methods For Analysis Of Datscan Spect Images, Hae Sol Moon

McKelvey School of Engineering Graduate Student Theses & Dissertations

There is an important need to develop biomarkers to improve the diagnosis and assess the severity of Parkinson’s disease (PD). The potential to derive such biomarkers from quantitative dopamine transporter scan (DaT-Scan) single-photon emission computed tomography (SPECT) imaging, in particular the uptake of DaT in the caudate, putamen, and globus pallidus regions, is highly appealing as imaging is non-invasive and DaTScan is already used in the management of patients with PD. However, reliable quantification requires reliable segmentation of these regions in these images. Reliable segmentation is challenging due to the limited spatial resolution and high image noise in SPECT images …

Multi-Dimensional Extension Of The Alternating Minimization Algorithm In X-Ray Computed Tomography, Jingwei Lu

McKelvey School of Engineering Graduate Student Theses & Dissertations

X-ray computed tomography (CT) is an important and effective tool in medical and industrial

imaging applications. The state-of-the-art methods to reconstruct CT images have had

great development but also face challenges. This dissertation derives novel algorithms to

reduce bias and metal artifacts in a wide variety of imaging modalities and increase performance

in low-dose scenarios.

The most widely available CT systems still use the single-energy CT (SECT), which is

good at showing the anatomic structure of the patient body. However, in SECT image

reconstruction, energy-related information is lost. In applications like radiation treatment

planning and dose prediction, accurate energy-related information …

Multi-Dimensional Extension Of The Alternating Minimization Algorithm In X-Ray Computed Tomography, Jingwei Lu

McKelvey School of Engineering Graduate Student Theses & Dissertations

X-ray computed tomography (CT) is an important and effective tool in medical and industrial imaging applications. The state-of-the-art methods to reconstruct CT images have had great development but also face challenges. This dissertation derives novel algorithms to reduce bias and metal artifacts in a wide variety of imaging modalities and increase performance in low-dose scenarios. The most widely available CT systems still use the single-energy CT (SECT), which is good at showing the anatomic structure of the patient body. However, in SECT image reconstruction, energy-related information is lost. In applications like radiation treatment planning and dose prediction, accurate energy-related information …

Preclinical Imaging Of Multiple Myeloma Therapy Response, Deep Hathi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Multiple myeloma (MM) is a debilitating hematologic malignancy of terminally differentiated plasma cells in the bone marrow (BM). Advances in therapeutic regimens and the use of autologous stem cell transplantation have significantly improved survival rates and quality of life in patients. However, the disease remains incurable, with shorter, successive remission cycles following relapse. To reduce systemic, off-target toxicity and improve quality of life, there is a need for improved stratification of responding patients. Identification of specific, noninvasive, imaging biomarkers that correlate to therapeutic efficacy is an attractive strategy for stratifying responding patients, since the use of positron emission tomography (PET), …

Regularized Fourier Ptychographic Microscopy, Shiqi Xu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Quantitative phase image (QPI) is a popular microscopy technique for studying cell morphology. Recently, Fourier ptychographic microscopy (FPM) has emerged as a low-cost computational microscopy technique for forming high-resolution wide-field QPI images by taking multiple images from different illumination angles. However, the applicability of FPM to dynamic imaging is limited by its high data requirement. In this thesis, we propose new methods for highly compressive FPM imaging using a data-adaptive sparse coding and an online plug-and-play (PnP) method with non-local priors based on the fast iterative shrinkage/threshold algorithm (FISTA). We validate the proposed method on both simulated and experimental data …

Basis Vector Model Method For Proton Stopping Power Estimation Using Dual-Energy Computed Tomography, Shuangyue Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate estimation of the proton stopping power ratio (SPR) is important for treatment planning and dose prediction for proton beam therapy. The state-of-the-art clinical practice for estimating patient-specific SPR distributions is the stoichiometric calibration method using single-energy computed tomography (SECT) images, which in principle may introduce large intrinsic uncertainties into estimation results. One major factor that limits the performance of SECT-based methods is the Hounsfield unit (HU) degeneracy in the presence of tissue composition variations. Dual-energy computed tomography (DECT) has shown the potential of reducing uncertainties in proton SPR prediction via scanning the patient with two different source energy spectra. …

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

McKelvey School of Engineering Graduate Student 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 Wavefront Shaping Techniques For Focusing Through Highly Dynamic Scattering Media, Ashton Hemphill

McKelvey School of Engineering Graduate Student 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 Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student Theses & Dissertations

In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing in vivo estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims …