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 …

Mri-Based Estimation Of The Hip Joint Center In Infants Using Two Sphere-Fitting Methods, Victoria Melendez

Discovery Day - Daytona Beach

Accurate estimation of the hip joint center (HJC) is critical for biomechanical modeling and clinical assessment. Common methods include predictive methods (e.g., regression equations) and functional methods such as sphere-fitting. In infants, femoral head-based methods are often limited due to incomplete ossification of the anatomy and poor visualization in computed tomography (CT) images. This study evaluates an alternative approach using MRI-based sphere fitting of the ossified acetabular rim, comparing its accuracy to traditional femoral head-based methods. MRI scans of three male infants (ages 10.7- 12.7 months) were used to manually place landmarks on the ossified acetabulum and the cartilaginous boundary …

Single Fluorogens And Orientation-Localization Microscopy For Quantifying Chemical And Biomolecular Dynamics At The Nanoscale, Yiyang Chen, Yuanxin Qiu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Many chemical systems look uniform only because ensemble measurements average over their most interesting molecules. Electron-transfer rates vary across electrode surfaces; lipid membranes contain nanodomains with distinct packing and fluidity; peptide aggregates exhibit local polymorphism; and biomolecular condensates contain transient networks of interactions that are blurred in ensemble images. A central challenge in chemical imaging is not simply to see smaller structures, but to measure chemical variables such as polarity, redox potential, and molecular confinement at the single-molecule level. In this Account, we describe how fluorogens, molecules whose brightness, blinking, spectral shifts, orientation, rotational mobility, and motion are directly shaped …

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 …

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 …

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 …

Characterizing Stiffness Dynamics Of Normal And Malignant Breast Spheroids Using Brillouin Microscopy, Razanne Rafat Zaghloul, Karlin Hilai, Chenjun Shi, Jitao Zhang

Medical Student Research Symposium

Background: Breast cancer progression and metastasis are closely linked to alterations in the mechanical properties of tumor cells and their microenvironment. Softer, more deformable cells are often associated with higher metastatic potential. While atomic force microscopy (AFM) is the current gold standard for mechanical characterization, it is limited to surface measurements and can damage 3D cultures. It remains unclear how the mechanical properties evolve over time in normal versus malignant spheroids. This study utilizes Brillouin light-scattering microscopy, a non-contact and label-free optical technique, to assess stiffness changes in normal and malignant breast epithelial spheroids over time. Understanding these mechanical signatures …

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 …

Sensing Negative-Cone Rotational Diffusion Of Dipole-Like Emitters, Yuanxin Qiu, Kaizhi A. Nie, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Fluorescence anisotropy and single-molecule orientation-localization microscopy (SMOLM) are powerful techniques that quantify the rotational diffusion of dipole-like emitters, which is important for sensing molecular interactions and chemical environments at the nanoscale. Numerous theoretical and experimental studies have thoroughly characterized single-molecule rotations even when those rotations are much faster than the detector integration time. Here, we extend the theory of measuring rotational diffusion to situations where a single dipole rotates uniformly everywhere outside of an isotropic cone of a certain size, termed a negative cone. This scenario corresponds to negative fluorescence anisotropy 𝑟 and has been observed in emitters exhibiting strong …

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 …

Influence Of Motion Artifacts On Instantaneous Frequency Based Heart Rate Variability Of Arterial Pulse Signals Measured By A Tactile Sensor: An Analytical Study, Mamun Hasan, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

Objective: Heart rate variability (HRV), quantified via the instantaneous frequency (IF) of arterial pulse signals, is a key indicator of cardiovascular (CV) regulation. This study presents a theoretical and experimental investigation of how motion artifacts (MA) influence IF-and thus HRVmeasured with a tactile sensor, emphasizing underlying mechanisms rather than population-level validation. Approach: Building on a previously developed single-degree-of-freedom (SDOF) model of the tissue-contact-sensor (TCS) stack between the sensor and the artery, MA is represented as low-frequency baseline drift and time-varying system parameters (TVSP) of the TCS stack. Analytical expressions quantify the effect of MA on the IF of each harmonic …

Fill The Void - An Introductory Guide For Learning Medical Imaging, Reid Faith, Peter Gahan, Adam Trusty, Aleksandr Zyskin, Chukwuka Ukekwe, Denise Nchinda, Amanda K. Burbage, Alberto E. Musto

EVMS School of Health Professions Faculty Publications

No standardized, comprehensive approach for radiological image interpretation exists among medical schools in the United States of America. In order to rectify this, we outline a model aimed to help improve how medical imaging can be taught in medical schools. The VOID (Visualization, Orientation/Observation, Identification, Description) guide is a proposed universal, stepwise approach to medical image identification, interpretation, and communication. This structured guideline is aimed at building a foundation for students in early medical education. The VOID was applied to CT (Computed Tomography), MRI (Magnetic Resonance Imaging), and x-ray modalities as integrated sessions for medical students during human anatomy laboratory. …

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 …

Training A Cellpose Model For T-Cell Cytoplasm And Nucleus Segmentation, William Laws, Matthew Lindley, Irene Georgakoudi

Wetterhahn Science Symposium Posters

Accurate single-cell segmentation of cytoplasm from nucleus in autofluorescence images is critical for quantifying cellular metabolism using the optical redox ratio (FAD / FAD+NAD(P)H). However, automated cytoplasmic segmentation of T cell two-photon excitation fluorescence images remains challenging due to low signal-to-noise ratio, small cell size, and variability in cell brightness across imaging conditions. Here, we present a pipeline combining a custom-trained Cellpose-SAM model with an adapted cytoplasmic post-processing algorithm (CPPA) for automated single-cell metabolic analysis of T cell NAD(P)H autofluorescence images. Raw 2048×2048 pixel images were spatially binned 4×4 in MATLAB to improve signal-to-noise ratio and reduce processing time. A …

Untrained Position-Encoded Multilayer Perceptron Network For Structured Illumination Microscopy Reconstruction, Sahil Sharma, Leonidas Zimianitis, Krishnendu Samanta, Balpreet Singh Ahluwalia, Joby Joseph, Dushan N. Wadduwage

Computer Science Faculty Publications

Structured Illumination Microscopy (SIM) enables super-resolution imaging by encoding high-frequency spatial information through patterned light. While traditional Fourier-based reconstruction methods are prone to artifacts under suboptimal conditions, recent deep learning approaches often require large training datasets and lack adaptability across different imaging setups. In this work, we present Position Encoded Multi-Layer Perceptron (PEM) network that leverages implicit neural representations (INRs) and SIM forward-model-driven modeling to reconstruct super-resolved images without any training data. PEM-SIM represents each spatial coordinate as a combination of sinusoidal functions across multiple frequencies, enabling rich encoding of fine spatial detail. A forward model grounded in SIM image …

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 …

Susceptibility To High-Fidelity Misinformation: An Eye-Tracking Analysis, Yasasi Abeysinghe, Gavindya Jayawardena, Enkelejda Kasneci, Sampath Jayarathna

Computer Science Faculty Publications

With the rise of online misinformation and AI-generated text, understanding human perception of news truthfulness is critical. In this study, we examine visual attention and cognitive processing using eye-tracking measures as individuals read fake and real news articles sharing nearly identical structure and imagery, differing only in subtle textual changes. Using the public FakeNewsPerception dataset, we analyze advanced gaze measures, including scanpaths, AOI transitions, and luminance-corrected pupil measures, beyond basic gaze features, in relation to news truthfulness and perceived believability. Results show that, given the high fidelity of the fake news, readers exhibited comparable visual scanning patterns, attention allocation across …

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 …

Single-Molecule Orientation And Localization Microscopy, Sophie Brasselet, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Single-molecule localization microscopy (SMLM) offers enhanced spatial resolution in optical microscopy, providing detailed insights into the spatial organization of proteins in cells at the nanoscale. Over the past decade, SMLM has progressively incorporated the capability to retrieve the orientations of single molecules using their polarized dipolar emission pattern. Here we explore recent advancements in single-molecule orientation and localization microscopy (SMOLM), which yields super-resolved images of molecular three-dimensional (3D) orientations, wobble and 3D positions. This advancement opens possibilities to explore the nanoscale organization and conformation of biological molecules as well as to monitor and design local 3D optical fields in nanophotonics. …

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 …