Bioimaging and Biomedical Optics Commons^™

Investigation Of The Effect Of Age On Regenerative Outcomes Following Treatment Of Volumetric Muscle Loss Injuries, John Taehwan Kim

Graduate Theses and Dissertations

Volumetric muscle loss (VML) is a traumatic injury in skeletal muscle resulting in the bulk loss of more than 20% of the muscle’s volume. Included in the bulk loss of muscle is the skeletal muscle niche comprised of nerve bundles, vasculature, local progenitor cells, basal lamina, and muscle fibers, overwhelming innate repair mechanisms. The hallmark of VML injury is the excessive accumulation of non-contractile, fibrotic tissue and permanent functional deficits. Though predominant in the younger demographic, the elderly population is also captured within VML injuries. There are many factors that change with aging in skeletal muscle that may further hinder …

Visualizing Ischemic Skin Flap Necrosis Through Phasor Analysis Of Autofluorescence Lifetime Images, Hallie Ramser Toomer

Graduate Theses and Dissertations

Necrotic skin flaps are difficult to predict and treat due to the lack of quantitative biomarkers. Label-free multiphoton microscopy is well suited for non-invasively monitoring skin metabolism through NAD(P)H and other intrinsic fluorophores, and offers immediate future directions for assessing necrosis in the clinic. The objective of this study was to assess whether phasor FLIM could be used to evaluate skin flap status and treatment efficacy in ex vivo skin sections. Phasor maps revealed differences in growth factor treatment and region, but changes in skin flap autofluorescence at 755nm excitation and 460nm emission were not just related to NAD(P)H. A …

Resolving Intravoxel White Matter Structures In The Human Brain Using Regularized Regression And Clustering, Andrea Hart, Brianna Smith, Sean Smith, Elijah Sales, Jacqueline Hernandez-Camargo, Yarlin Mayor Garcia, Felix Zhan, Lori Griswold, Brian Dunkelberger, Michael R. Schwob, Sharang Chaudhry, Justin Zhan, Laxmi Gewali, Paul Oh

Computer Science Faculty Research

The human brain is a complex system of neural tissue that varies significantly between individuals. Although the technology that delineates these neural pathways does not currently exist, medical imaging modalities, such as diffusion magnetic resonance imaging (dMRI), can be leveraged for mathematical identification. The purpose of this work is to develop a novel method employing machine learning techniques to determine intravoxel nerve number and direction from dMRI data. The method was tested on multiple synthetic datasets and showed promising estimation accuracy and robustness for multi-nerve systems under a variety of conditions, including highly noisy data and imprecision in parameter assumptions.

Using Feature Extraction From Deep Convolutional Neural Networks For Pathological Image Analysis And Its Visual Interpretability, Wei-Wen Hsu

Electrical & Computer Engineering Theses & Dissertations

This dissertation presents a computer-aided diagnosis (CAD) system using deep learning approaches for lesion detection and classification on whole-slide images (WSIs) with breast cancer. The deep features being distinguishing in classification from the convolutional neural networks (CNN) are demonstrated in this study to provide comprehensive interpretability for the proposed CAD system using the domain knowledge in pathology. In the experiment, a total of 186 slides of WSIs were collected and classified into three categories: Non-Carcinoma, Ductal Carcinoma in Situ (DCIS), and Invasive Ductal Carcinoma (IDC). Instead of conducting pixel-wise classification (segmentation) into three classes directly, a hierarchical framework with the …

Spatial Frequency Domain Imaging Of Short-Wave Infrared Fluorescence For Biomedical Applications, Joseph P. Leonor

ENGS 88 Honors Thesis (AB Students)

Fluorescence imaging has become a standard in many clinical applications, such as tumor and vasculature imaging. One application that is becoming more prominent in cancer treatment is fluorescence-guided surgery (FGS). Currently, FGS allows surgeons the ability to visually navigate tumors and tissue structures intraoperatively. As a result, they can remove tumor more efficiently while maintaining critical structures within the patient, creating better outcomes and lower recovery times. However, background fluorescence and inability to localize depth create challenges when determining resection boundaries.

Different techniques, such as spatially modulating the illumination and imaging at longer light wavelengths, have been developed to accurately …

Evaluation Of Human Umbilical Vein Endothelial Cells In Blood Vessel Mimics Through Changes In Gene Expression And Caspase Activity, Conor Charles Hedigan

Master's Theses

Blood vessel mimics (BVMs) are simple tissue engineered blood vessel constructs intended for preclinical testing of vascular devices. This thesis developed and implemented methods to characterize two of these components. The first aim of this thesis investigated the effect of cell culture duration and flow conditions on endothelial cell gene expression, especially regarding endothelial-to-mesenchymal transition (EndMT). A trend of decreased endothelial marker gene expression and increased mesenchymal marker gene expression would indicate EndMT. qPCR analysis revealed that increased cell culture duration did not result in EndMT, and in fact increased endothelial marker expression as cell culture duration increased. Disturbed flow …

A Multimodal Approach To Investigate Brain Reorganization After Spinal Cord Injury Using Functional Magnetic Resonance Imaging And Functional Near-Infrared Spectroscopy, Keerthana Deepti Karunakaran

Dissertations

Traumatic Spinal Cord Injury (SCI) results in structural and functional neurological changes at both the brain and the level of the spinal cord. Anatomical studies indicate decreased grey matter volume in sensorimotor and non-sensorimotor regions of the cortex following SCI; whereas, neurophysiological findings mostly report altered functional activity in the sensorimotor nodes of the cortex, subcortex, and cerebellum. Therefore, it is currently unknown whether tissue atrophy observed in non-motor related areas has any concomitant functional consequences. Furthermore, the neural underpinnings of adaptive neuroplasticity after SCI is not well-defined in the current literature. Hence, this dissertation is a pioneer study investigating …

Dual Modality Optical Coherence Tomography : Technology Development And Biomedical Applications, Farzana Rahmat Zaki

Dissertations

Optical coherence tomography (OCT) is a cross-sectional imaging modality that is widely used in clinical ophthalmology and interventional cardiology. It is highly promising for in situ characterization of tumor tissues. OCT has high spatial resolution and high imaging speed to assist clinical decision making in real-time.

OCT can be used in both structural imaging and mechanical characterization. Malignant tumor tissue alters morphology. Additionally, structural OCT imaging has limited tissue differentiation capability because of the complex and noisy nature of the OCT signal. Moreover, the contrast of structural OCT signal derived from tissue’s light scattering properties has little chemical specificity. Hence, …

A Simplified Crossing Fiber Model In Diffusion Weighted Imaging, Sheng Yang, Kaushik Ghosh, Ken Sakaie, Satya S. Sahoo, Sarah J. Ann Carr, Curtis Tatsuoka

Mathematical Sciences Faculty Research

Diffusion MRI (dMRI) is a vital source of imaging data for identifying anatomical connections in the living human brain that form the substrate for information transfer between brain regions. dMRI can thus play a central role toward our understanding of brain function. The quantitative modeling and analysis of dMRI data deduces the features of neural fibers at the voxel level, such as direction and density. The modeling methods that have been developed range from deterministic to probabilistic approaches. Currently, the Ball-and-Stick model serves as a widely implemented probabilistic approach in the tractography toolbox of the popular FSL software package and …

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), …

Vector Flow Imaging In Pediatric Cardiology - Extracting And Validating Data, Mason Belue

Biomedical Engineering Undergraduate Honors Theses

In the field of bedside cardiac diagnostic imaging, Doppler Ultrasound (DU) is the gold standard for diagnosing heart conditions. The largest benefit of DU is its ability to noninvasively image cardiac flow and allow the estimation of blood velocity and quantification of anatomical disease. However, to get correct velocity estimation, the position of the transducer in relation to the flow field needs to be known. This is the problem of angle/direction dependency and limits DUs accuracy when imaging in areas where perfect alignment or exact position of the transducer in relation to flow field is not possible or known, such …

Investigation Of Acute Radiation-Induced Changes In Oxygenation In A Murine Breast Tumor Model, Alaa Abdelgawad

Biomedical Engineering Undergraduate Honors Theses

Around 50-60% of all cancer patients undergo radiation therapy. Although some patients show complete response with no recurrence, a significant proportion of the population still develop radiation resistance. It is important to identify tumor resistance at early stages of therapy in order to adjust treatment protocol and avoid extra exposure to radiation. Current methods to assess treatment response are only limited to anatomical measurements of tumor volume after therapy. Novel approaches that shed the light on any functional information during the course of radiotherapy could significantly improve our ability to identify patients who do not respond to radiation therapy. Diffuse …

Cell Imaging And Data Analysis For Biomaterial-Mammalian Co-Cultures, Jefferson Pontsler

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Microscopic bioimaging is a useful approach to study cell-biomaterial interactions which are vital to the biomedical application of biomaterials. Through microscopic imaging, numerous cellular responses, such as proliferation, uptake, and death, can be recorded, characterized and analyzed.

In this thesis, I first provided basic introductions to the imaging techniques and analysis tools, especially those that are highly relevant to the studies of biomaterials and cell interactions. I also detailed the adaptation of these techniques and tools in the application of two specific research projects in biomaterials, with special focuses on the imaging and analysis.

The first project assessed the subtle …

Seeing Eye To Eye: A Machine Learning Approach To Automated Saccade Analysis, Maigh Attre

Honors Scholar Theses

Abnormal ocular motility is a common manifestation of many underlying pathologies particularly those that are neurological. Dynamics of saccades, when the eye rapidly changes its point of fixation, have been characterized for many neurological disorders including concussions, traumatic brain injuries (TBI), and Parkinson’s disease. However, widespread saccade analysis for diagnostic and research purposes requires the recognition of certain eye movement parameters. Key information such as velocity and duration must be determined from data based on a wide set of patients’ characteristics that may range in eye shapes and iris, hair and skin pigmentation [36]. Previous work on saccade analysis has …

Autofluorescence To Study The Effects Of Acid Concentration On Cellular Metabolism In Vitro, Robin L. Raley

Chemistry & Biochemistry Undergraduate Honors Theses

Ultraviolet (UV) radiation-induced sunburns and their accompanying afflictions are a growing public health concern in the United States. There is a need for techniques that can accurately and non-invasively characterize the physiology of sunburned skin tissue directly after UV-damage and applying a topical skin treatment to relieve pain and promote healing. Two-photon excited fluorescence (TPEF) microscopy and fluorescence lifetime imaging (FLIM) can be used to investigate metabolic processes in live cells through endogenous fluorescence of the cofactors, NADH and FAD. These methods employ the optical redox ratio of FAD/(NADH+FAD), mean NADH lifetime, and the separation of the free and bound …

Modeling And Validation Of Tissue Optical Properties In The Photon Transport Regime, Katelyn Heath

Biomedical Engineering Undergraduate Honors Theses

Early detection of changes in epithelial cells, such as the development of neoplastic formations seen in epithelial dysplasia, can indicate regions of the epithelial tissue that are at a high risk for cancerous formation. Using concepts from diffuse reflectance spectroscopy, a Monte Carlo model was developed to predict the reflectance measured by a detector at a small source-detector separation on a microendoscope. The Monte Carlo results were then used to calculate a mathematical relationship between the reflectance and distance that can be used to determine optical properties in a tissue sample. This model was validated with liquid phantoms of specified …

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Graduate Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and …

Biomedical Engineering Or Biomedical Optics: Will The Real Discipline Please Stand Up?, Brian W. Pogue

Dartmouth Scholarship

This editorial reflects on the shape of biomedical engineering as a discipline, and its relation to biomedical optics.

Quantifying Iron Overload Using Mri, Active Contours, And Convolutional Neural Networks, Andrea Sajewski, Stacey Levine

Undergraduate Research and Scholarship Symposium

Iron overload, a complication of repeated blood transfusions, can cause tissue damage and organ failure. The body has no regulatory mechanism to excrete excess iron, so iron overload must be closely monitored to guide therapy and measure treatment response. The concentration of iron in the liver is a reliable marker for total body iron content and is now measured noninvasively with magnetic resonance imaging (MRI). MRI produces a diagnostic image by measuring the signals emitted from the body in the presence of a constant magnetic field and radiofrequency pulses. At each pixel, the signal decay constant, T2*, can be calculated, …

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 …