Bioimaging and Biomedical Optics Commons^™

Compact 1 Ghz Electron Paramagnetic Resonance Spectrometers For Preclinical Imaging Studies, Tanden A. Hovey

Electronic Theses and Dissertations

Magnetic resonance is one of the most generally useful scientific techniques. New horizons of understanding are revealed as technological advances make possible explorations of nuclear spins and electron spins at higher and lower magnetic fields and electromagnetic frequencies. While the greatest current effort is on ever higher magnetic fields and microwave frequencies, both in nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR), the Eaton lab focusses on developing high signal-to-noise performance EPR at low microwave frequencies. EPR provides information about O2, pH, viscosity, glutathione concentrations, and reactive oxygen species in living organisms that MRI cannot. To yield clinically or …

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 …

Fluorescence Cryotomography For Preclinical Validation: Applications In Gene Therapy And Fluorescence-Guided Surgery, Caleb Y. J. Kwon

Dartmouth College Ph.D Dissertations

Fluorescence imaging has become a powerful tool in biomedical research and clinical practice, offering molecular specificity and high sensitivity for visualizing biological processes in real time, However, the successful translation of novel fluorescent probes or medicines from preclinical development to clinical applications requires rigorous validation of their biodistribution and target specificity. Traditional methods for assessing performance, such as bulk excised organ analysis or two-dimensional histology, provide limited information as they cannot capture the complete, organism-wide distribution of these probes or medicines. This thesis aims to improve this analysis pipeline through the application and optimization of fluorescence cryotomography for quantitative, high-resolution …

The Effects Of Adipose Tissue Trauma On Vascular Function After Collateral Arteriogenesis, Nathan Tran

Biomedical Engineering

Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is characterized by arterial narrowing that reduces perfusion to the limbs. Collateral arterioles can naturally restore blood flow through a remodeling process called arteriogenesis, making it a promising therapeutic target. However, the femoral artery ligation (FAL) model used to study arteriogenesis requires surgical access deep to the inguinal fat pad, and approaches for handling the fat pad vary widely across surgeons and protocols. Since adipose tissue harbors a large population of macrophages, the immune cells that govern arteriogenesis, fat pad manipulation may introduce confounding inflammatory stimuli that disrupt …

Evaluation Of Medical Instrument Reliability For The Heath And Maddox Components Of The Accommodative-Vergence System, Jacob Chabuel

Theses

Binocular vision relies on the coordination of near response triad composed in part by the vergence and accommodative systems. Binocular dysfunctions linked to these systems impact the quality of life of those affected by complicating day-to-day tasks and leading to further health concerns. Clinical evaluations that diagnose dysfunctions and tailor therapies rely on subjective methods, creating a need for a reliable, quantitative, measurement tool. This is achieved using a haploscope, a tool that quantitatively measures and observes binocular vision to identify deficiencies within the eye. Modernization of a haploscope system, measurement of the Heath and Maddox components of the visual …

Robustness Of Ai-Driven Histopathology Under Real-World Adversarial Examples, Ruchik N. Yajnik

Theses

This robustness of histopathology classification models under adversarial and real-world perturbations resembling clinical artifacts is being investigated.

Using whole-slide images from the CAMELYON17 cohort, four representative architectures—ResNet-18, ResNet-50, HIPT-2MLP, and ViT-B/16 —are benchmarked across controlled pixel-level distortions and artifact-like transformations. Adversarial methods include iterative Fast Gradient Sign, Projected Gradient Descent, Salt-and-Pepper noise, and the Adversarial Watermark—Stain Shift (AWSS). Three defense strategies—Randomized Smoothing, Adversarial Training, and an Artifact Detector—are evaluated for their ability to preserve diagnostic accuracy and model reliability. Structured perturbations consistently degrade performance, with transformer-based models showing the greatest sensitivity. The benchmark developed here offers a reproducible framework for …

Vergence Task-Based Neural Pathways With Binocularly Normal Vision And Comorbid Persistent Post-Concussive Symptoms -Convergence Insufficiency, Ayushi Sangoi

Dissertations

Binocular dysfunctions are more prevalent in the persistent post-concussive symptoms (PPCS) population than in the general population. The most prevalent binocular disorder is convergence insufficiency (CI), affecting 3-17% of the general population and up to 10 times as many people with PPCS. CI makes it difficult to fuse or maintain fusion on targets at near, and its symptoms include double or blurry vision and headaches when performing close-range tasks such as reading, which can exacerbate PPCS symptoms. Given controversy over the subjectivity and effectiveness of diagnostic tools and symptom surveys for both PPCS and CI, understanding why CI has high …

Spectral Characterization Of Colorectal Cancer Using Excitation-Scanning Hyperspectral Imaging, Natalie Hadad

Honors Theses

Colorectal cancer is one of the most common and deadly cancers worldwide, with a lifetime risk of approximately one in twenty-three for men and one in twenty-five for women. Although early detection significantly improves survival, current diagnostic approaches such as tissue biopsy are invasive, reliant on subjective interpretation, have extended turnaround times, and risk missing flat or depressed lesions that are more difficult to detect than raised polyps. These limitations highlight the need for objective, minimally invasive technologies capable of detecting early tissue changes. This study investigates excitation-scanning hyperspectral imaging (Ex-HSI) as a label-free optical approach for identifying colorectal cancer–associated …

Quantitative Fluorescence Imaging Using A Paired Agent Approach For Improving Surgical Decision Making, Sanjana Pannem

Dartmouth College Ph.D Dissertations

Surgical resection remains to be the cornerstone of treatment for most solid tumors, where the primary objective is to remove all visible and microscopic disease. However, the extent of tumor resection is inherently limited by the surgeon’s ability to distinguish tumor from normal tissue, intraoperatively. As a result, positive surgical margins (PSM), where residual tumor remains after surgery, are a common occurrence and are associated with increased recurrence, need for adjuvant therapies, dismal patient outcomes, and high healthcare costs.

Fluorescence guided surgery (FGS) has emerged as a promising technique to enhance intraoperative visualization of tumors and may help reduce the …

Advancing Computational Analysis Of Fluorescence Imaging For Head And Neck Cancer Surgical Guidance, Yao Chen

Dartmouth College Ph.D Dissertations

The main goal of surgery for head and neck squamous cell carcinoma (HNSCC) is to remove the tumor completely while preserving as much healthy tissue as possible to enhance patient survival and reduce complications. However, achieving clear surgical margins is difficult due to the complex anatomy of the head and neck and the reliance on a surgeon’s visual and tactile assessments. Recently, near-infrared (NIR) fluorescence molecular imaging has shown potential for better tumor visualization during surgery, using targeted imaging agents like epidermal growth factor receptor (EGFR) probes. This has led to the development of fluorescence-guided surgery (FGS), which helps surgeons …

Mechanical Characterization And Modeling Of Rat Myocardia Under The Influence Of Epirubicin, Abdallah Mahmoud Alkhaiyat

Theses and Dissertations

Cancer remains a predominant health challenge that is responsible for a significant portion of global morbidity and mortality. Epirubicin (EPI), a chemotherapeutic anti-cancer drug, has shown remarkable efficacy in combating various malignancies. However, it is known to have undesirable side effects on the heart, collectively referred to as cardiotoxicity. This research investigates the adverse effects of chemotherapy on cardiac contractility through an in vitro examination of the mechanics of healthy and infarcted animal heart tissues. Electrically stimulated slices of rat ventricular tissue were tested using an isometric force measurement tissue bath. The tissue slices were subjected to uniaxial stretching, allowing …

Methods For Radiation-Sparing Navigation In Endovascular And Spine Surgery, William Ross Warner

Dartmouth College Ph.D Dissertations

Modern surgical navigation systems improve procedural accuracy, limit complications, and can reduce reliance on intraoperative ionizing radiation, yet their adoption remains uneven across surgical domains. Informed by clinical immersion, this thesis identifies and addresses two unmet needs revealed through contrasting image-guidance practices in endovascular and spine surgery, where existing guidance techniques are costly, intermittent, or fundamentally limited. Specifically, these needs include (1) the absence of radiation-sparing navigation techniques for endovascular procedures, which rely heavily on 2D x-ray angiography, and (2) the need for dynamic registration methods in open spine surgery, where navigation accuracy can degrade after initial registration and intraoperative …

Early Detection And Objective Assessment Of Neonatal Hypoxic-Ischemic Encephalopathy Severity, Soheila Norasteh

Bioengineering Dissertations

Hypoxic–ischemic encephalopathy (HIE) is a neonatal brain injury caused by reduced oxygen and blood flow to the brain around the time of birth. It remains a major cause of neonatal mortality and long-term neurodevelopmental impairment worldwide. Therapeutic hypothermia is the standard treatment for moderate-to severe HIE and improves outcomes when initiated within the first six hours of life. Therefore, accurate assessment of injury severity during this period is essential. Cur rently, HIE severity is determined primarily through neurological examination and classified as mild, moderate, or severe. However, these examinations are subjective, cannot provide continuous monitoring of brain function, and may …

Adversarial Robustness In Biomedical Time-Series Models, Rohan Tiwari

Bioengineering Theses

This study investigates adversarial vulnerabilities in deep learning models for biomedical time-series classification across two clinically important modalities: electrocardiography (ECG) and electroencephalography (EEG). Using the MIT-BIH Arrhythmia and CHB-MIT seizure datasets, I evaluate time-domain attacks (FGSM, PGD), Fourier-domain constrained attacks, and learned spectral perturbations designed to reveal modality-specific sensitivity patterns. Across both tasks, a consistent trend emerges low-frequency components (0–5 Hz) constitute a dominant axis of adversarial vulnerability, with perturbations in this range producing the steepest degradation in classification performance. In ECG models, protecting the physiologically relevant QRS band (5–20 Hz) significantly improves robustness, whereas EEG models remain highly sensitive …

Volumetric Fluorescence Microscopy For High-Throughput And High-Sensitivity Imaging: From Single Molecules To Tissues, Le-Mei Wang

Graduate Studies Theses and Dissertations 2026

Fluorescence microscopy is an indispensable tool in the biological sciences, enabling researchers to investigate intricate subcellular structures, particularly for volumetric studies. However, conventional optical microscopy for volumetric imaging remains fundamentally constrained by imaging speed and throughput. To bypass traditional serial z-scanning, we introduce an axially scan-free method using a phase layer cake to modulate the system's point spread function. This approach projects volumetric information onto a 2D plane in a single shot, offering high flexibility in tuning axial depth alongside simultaneous multicolor imaging with high spatial resolution and sensitivity. This dissertation divides these technical advancements into cellular and tissue imaging …

On The Scalability Of Anisotropic Mesh Adaptation On Distributed And Shared Memory Architectures For Numerical Approximations, Kevin Mark Garner Jr.

Computer Science Theses & Dissertations

Mesh generation is a critical component in numerical approximations of Partial Differential Equations (PDEs). One such example includes Computational Fluid Dynamics (CFD), as CFD simulations in turn are crucial for applications in many industries, such as personalized healthcare and the design of aerospace vehicles. Generating high quality meshes for large-scale CFD problems presents a significant bottleneck in the CFD workflow. This dissertation proposes “fast,” parallel 3D mesh generation methodologies that are designed to leverage the concurrency offered by emerging High-Performance Computing (HPC) architectures. First, a distributed memory method is presented that integrates a sequential state-of-the-art isotropic, advancing front local reconnection-based …

Reproducibility In Modeling Of Knee Joint Mechanics, Maryam Nazem

Electronic Theses and Dissertations

Computational modeling of knee joint biomechanics can provide valuable insights into joint function, injury mechanisms, and patient outcomes, and can support surgical planning and informed clinical decision-making. However, achieving consistent and repeatable results, or reproducibility, is a significant challenge that affects the credibility of these models. This thesis addresses reproducibility through two studies related to the KneeHub Project, which is a multi-institutional collaboration designed to investigate reproducibility in finite-element modeling of the knee.

The first study involved model benchmarking, where predicted results of the calibrated models were compared with the experimental data to evaluate model reproducibility. While all models replicated …

A Convolutional Neural Network Approach To Breast Cancer Tumor Boundary Detection, James Leah Matlosz

Master's Theses

Breast cancer is the second most common form of cancer and often goes undetected in its initial stages due to its subtle symptoms. As the tumors grow, they become more difficult to surgically remove with clean borders. To minimize the chance of recurrence, a 2D convolutional neural network is developed in this work for delineating tumor boundaries. Specifically, the U-shaped network model is trained, validated, and tested with longitudinal MRI scans of patients diagnosed with breast cancer and undergoing neoadjuvant therapy. For training, image masks were generated as ground truths using signal enhancement ratio segmentation, thresholding, and contour detection. The …

Low-Cost Cutaneous Protoporphyrin Ix (Ppix) Detection (Cpd) Device For Follow-Up Monitoring Of Patients After Photodynamic Therapy, Md Asaduzzaman Rasel

Graduate Masters Theses

Background: Photodynamic Therapy (PDT) utilizes specific wavelengths of light to activate photosensitizing chemical compounds, known as photosensitizers, which induce the generation of cytotoxic reactive oxygen species (ROS) for the targeted destruction of cancer cells. Among various photosensitizers for PDT, Protoporphyrin IX (PpIX) is widely employed in oncology and dermatology due to its natural in situ generation via the metabolic conversion of 5- aminolevulinic acid (ALA), a non-phototoxic prodrug. Systemic administration of ALA after 3-6 hr drug delay leads to peak PpIX accumulation in tissues, facilitating therapeutic and diagnostic applications. However, PpIX can persist in the skin for 24–48 hours post-treatment, …

Design And Development Of A Standalone Digital Holographic Microscope Employing Phase-Driven Reconstruction And Classification For Biomedical Imaging And Optical Diagnostics, Charlotte Kyeremah

Graduate Doctoral Dissertations

Access to advanced biomedical imaging technologies remains a significant challenge in resource-limited settings, especially for early disease detection and monitoring of diseases such as malaria, HIV, and other blood-borne diseases. Although point-of-care (POC) devices have gained popularity in global health, many rely on antibody-based tests, lateral flow strips, or optical readouts that often lack quantitative capabilities, sensitivity to early infections, or versatility in different diagnostic targets. In addition, these systems are typically dependent on disposable reagents or manual interpretation, which limits their effectiveness in remote areas. Digital Holographic Microscopy (DHM) presents a promising alternative as a label-free imaging method capable …

Volumetric Imaging Of Cellular Dynamics Using Light-Sheet Microscopy: From Subcellular Structures To Whole Organisms, Md Nasful Huda Prince

Optical Science and Engineering ETDs

Advancing biomedical imaging requires platforms that combine high-resolution, speed, and stability across biological scales. This dissertation presents three innovations designed to address limitations of conventional light-sheet and oblique plane imaging. First, we introduce Reflected Inline Detection in Epi-Oblique Plane Microscopy (RIDE-OPM), a compact and drift-resistant system that eliminates a tertiary detection path while maintaining alignment flexibility, enabling robust long-term live imaging. Second, we present a high-speed Axially Swept Light-Sheet Microscopy (ASLM) platform for cleared tissues, using dual foci and synchronized sweeping to achieve isotropic sub-micron resolution at up to 40 frames-per-second, a fourfold improvement over standard ASLM. Integrated with a …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Computational Fluid Dynamics And Fluid Structure Interaction Modeling In Healthy Vertebral Arteries: A Comparative Study, Bryce Clinkenbeard

Electronic Theses and Dissertations

Cerebral perfusion is critical for maintaining proper brain function, with each cerebrovascular artery playing an integral role in the overall cerebrovascular system. When these arteries become damaged or develop plaque, cardiovascular disease (CVDs) such as atherosclerosis can arise, leading to conditions like arterial stenosis. While CVDs are most prevalent in older individuals, they are also observed in young adults, particularly those engaged in high-endurance occupations such as military service. Diagnosis and prediction of CVDs often rely on imaging modalities supported by computational fluid dynamics (CFD) which account for low resolution in fluid flow. CFD models assume rigid arterial walls, which …

Acoustic And Hemodynamic Analysis Of Phantoms: Roughness And Flow Dynamics, Ethan Erik Olof Sundberg

Master's Theses

The purpose of this study was to determine whether different vascular phantoms, with and without a surrogate arm, could serve as effective analogs to the human brachial artery for assessing endothelial dysfunction, an early indicator of cardiovascular disease, particularly atherosclerosis. Atherosclerosis is characterized by plaque buildup and endothelial damage, which precede more severe clinical events and are often detectable through changes in vascular function. A 40” water tower was used to simulate diastolic pressure, enabling water flow through each phantom. Strain gauge pressure transducers were placed at both ends of the phantoms to measure pressure drop, while a microphone captured …

Intraoperative Dynamic Contrast-Enhanced Fluorescence Imaging For Navigating Open Orthopedic Surgeries, Yue Tang

Dartmouth College Ph.D Dissertations

Infection following trauma is one of the most prevalent and challenging complications faced by orthopedic surgeons. Inadequate tissue perfusion plays a critical role in this complication, as poorly perfused bone can be a nidus for bacterial biofilm formation and promote resistance to antibiotic treatments. Consequently, the management of open fractures and fracture-related infections relies on aggressive and thorough debridement to remove all poorly perfused bone. This thesis focuses on developing an indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) to objectively measure bone perfusion during open orthopedic surgeries and guide surgical debridement of devitalized bone.

Novel methodologies were developed to …

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 …

Multi-Modal Mri For The Pre-Clinical Evaluation Of Hiv-Linked Changes In The Central Nervous System, Gabriel Gauthier

Theses & Dissertations

Though the inception of anti-retroviral therapy (ART) has fundamentally changed the life expectancy of human immunodeficiency virus (HIV) patients, accessibility and outcomes vary enormously along demographic lines. Even for people living with HIV (PLWH) with perfect access and adherence to anti-retroviral drugs (ARVs), modern treatment plans are fundamentally unable to secure complete viral remission for patients. The cause of this perpetual infection is the persistence of viral reservoirs in the central nervous system (CNS), hidden beyond the reach of modern ARVs, leaving patients to deal with lifelong medication side-effects and risks of developing HIV-associated neurodegenerative disorders (HAND). Despite improving outcomes …

Alterations And Improvements Of The Photoacoustic Flow Cytometry Method, Nicholas J. Taylor

Electronic Theses and Dissertations

The emergence and proliferation of antibiotic-resistant bacteria present a significant and growing challenge to global public health, with the potential to render many existing antibiotics ineffective. Infections caused by these resistant pathogens are difficult to treat, resulting in higher morbidity, mortality, and healthcare costs. A major obstacle in combating these infections is the slow pace of traditional diagnostic methods, such as blood cultures, which typically take 2-3 days to identify the causative bacteria and determine their antibiotic resistance profiles. This delay in diagnosis hinders timely interventions and appropriate treatment, further contributing to the spread of resistant infections. As such, there …

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 …

Development Of Translational Microscale Systems To Interrogate How Biophysical And Biochemical Cues Alter The Phenotype Of Hormone Positive Breast Cancer, Braulio Ortega Quesada

All Dissertations

Cancer is a complicated disease and one in every three diagnoses are women with breast cancer. Recent research shows that the progression of cancer depends strongly on interactions with other non-cancerous cells and non-cellular components. Metastasis, the spread of cancer to other parts of the body, is a key step in cancer progression and makes treatment harder, leading to poor response to treatments culminating in death in ~90% of patients. This dissertation focused on creating a series of microdevices as novel pre-clinical models of breast cancer. Two different devices were fabricated to (1) study how exposing cancer cells to the …