Bioimaging and Biomedical Optics Commons^™

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 …

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 …

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 …

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 …

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 …

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.

A Structured-Light Surface Scanning System To Evaluate Breast Morphology In Standing And Supine Positions, Olivia Tong

Electronic Thesis and Dissertation Repository

Objective and accurate surface measurements of the human breast are important for surgical planning and outcome assessment. Breast shapes are affected by gravitational loads and deformities, and the measurements obtained in the standing position may not correlate well with measurements in supine position, which is more representative of breast surgery. To evaluate the effect of changes in body posture on breast morphology, a dual color 3D surface imaging system capable of scanning patients in both the supine and standing positions was developed. System performance was established by assessing the surface coverage and accuracy between a CAD breast model and 3D …

Tissue Equivalent Gellan Gum Gel Materials For Clinical Mri And Radiation Dosimetry, Pawel Brzozowski

Electronic Thesis and Dissertation Repository

Hydrogels contain high amount of water allowing their use as surrogates to human tissues with specific properties that can be tuned by additives. Gellan gum is a gel-forming material of interest and is a replacement for other common gelling agent with limited use as a tissue phantom. Therefore, this thesis examines the application of gellan gum gels as a novel magnetic resonance imaging (MRI) phantom with a design of experiments model to obtain tunable properties. The analysis was extended to include mechanical and electrical properties with a separate design of experiment. Gels doped with synthesized superparamagnetic iron oxide nanoparticles (SPIONs) …

Improving Material Mapping In Glenohumeral Finite Element Models: A Multi-Level Evaluation, Nikolas K. Knowles

Electronic Thesis and Dissertation Repository

An improved understanding of glenohumeral bone mechanics can be elucidated using computational models derived from computed tomography data. Although computational tools, such as finite element analysis, provide a powerful quantitative technique to evaluate and answer a variety of biomechanical and clinical questions, glenohumeral finite element models (FEMs) have not kept pace with improvements in modeling techniques or model validation methods seen in other anatomic locations. The present work describes the use of multi-level computational modeling to compare, develop and validate FEMs of the glenohumeral joint.

Common density-modulus relationships within the literature were evaluated using a multi-level comparative testing methodology to …

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 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 …

Characterizing Short-Wave Infrared Fluorescence Of Conventional Near-Infrared Fluorophores, Brook K. Byrd, Margaret R. Folaron, Joseph P. Leonor, Rendall R. Strawbridge, Xu Cao, Petr Bruza, Scott C. Davis

Dartmouth Scholarship

The observed behavior of short-wave infrared (SWIR) light in tissue, characterized by relatively low scatter and subdiffuse photon transport, has generated considerable interest for the potential of SWIR imaging to produce high-resolution, subsurface images of fluorescence activity in vivo. These properties have important implications for fluorescence-guided surgery and preclinical biomedical research. Until recently, translational efforts have been impeded by the conventional understanding that fluorescence molecular imaging in the SWIR regime requires custom molecular probes that do not yet have proven safety profiles in humans. However, recent studies have shown that two readily available near-infrared (NIR-I) fluorophores produce measurable SWIR fluorescence, …

Automated Microscope Stage, Corin Nishimoto, Alison Flesch, Theo Anastos

Biomedical Engineering

This document seeks to describe the background information, customer requirements, design specifications, indications for use, selected materials, proposed budget, prototypes, final design, manufacturing processes, and testing methods regarding the CellOptimizer automated microscope stage product.

Long-Term, Super-Resolution Imaging Of Amyloid Structures Using Transient Amyloid Binding Microscopy, Tianben Ding, Kevin Spehar, Jan Bieschke, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid fibrils and tangles are signatures of Alzheimer disease, but nanometer-sized aggregation intermediates are hypothesized to be the structures most toxic to neurons. The structures of these oligomers are too small to be resolved by conventional light microscopy. We have developed a simple and versatile method, called transient amyloid binding (TAB), to image amyloid structures with nanoscale resolution using amyloidophilic dyes, such as Thioflavin T, without the need for covalent labeling or immunostaining of the amyloid protein. Transient binding of ThT molecules to amyloid structures over time generates photon bursts that are used to localize single fluorophores with nanometer precision. …

Diagnostic Performance Of Receptor-Specific Surgical Specimen Staining Correlates With Receptor Expression Level, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Intraoperative margin assessment is imperative to cancer cure but is a continued challenge to successful surgery. Breast conserving surgery is a relevant example, where a cosmetically improved outcome is gained over mastectomy, but re-excision is required in >25  %   of cases due to positive or closely involved margins. Clinical translation of margin assessment modalities that must directly contact the patient or required administered contrast agents are time consuming and costly to move from bench to bedside. Tumor resections provide a unique surgical opportunity to deploy margin assessment technologies including contrast agents on the resected tissues, substantially shortening the path to …

Ensuring Scientific Publishing Credibility In Translational Biomedical Optics., Brian W. Pogue

Dartmouth Scholarship

Optics has consistently been the largest singular technology sector used in medicine, and major advances in biomedical optics are documented daily in peer-reviewed publications. However, the academic stature of this field can be damaged by weaknesses in scientific publishing, where a “credibility crisis” has emerged as a popularized and increasingly studied dialogue. While there are still relatively few overt cases of fraud or erroneous research, more insidious aspects are seen in papers with results that have either low statistical power, selective reporting of observations, or data or computer codes that cannot be independently verified. Interestingly, the same solutions that improve …

Quantification Of Myocardial Mechanics In Left Ventricles Under Inotropic Stimulation And In Healthy Right Ventricles Using 3d Dense Cmr, Zhan-Qiu Liu

Theses and Dissertations--Mechanical Engineering

Statistical data from clinical studies indicate that the death rate caused by heart disease has decreased due to an increased use of evidence-based medical therapies. This includes the use of magnetic resonance imaging (MRI), which is one of the most common non-invasive approaches in evidence-based health care research. In the current work, I present 3D Lagrangian strains and torsion in the left ventricle of healthy and isoproterenol-stimulated rats, which were investigated using Displacement ENcoding with Stimulated Echoes (DENSE) cardiac magnetic resonance (CMR) imaging. With the implementation of the 12-segment model, a detailed profile of regional cardiac mechanics was reconstructed for …

Utilizing Immunopet To Measure Tumor Response To Treatment In Breast Cancer, Brooke Mcknight

Wayne State University Dissertations

With a broad spectrum of therapies available for treating breast cancer, the need for personalized medicine tailoring the cure according to phenotype is evident. Such an approach may be fully realized with the development of quantitative imaging technologies for disease detection, staging and diagnosis, without increasing patient burden. Immuno-positron emission tomography (PET) combines the targeted specificity of antibodies with the sensitivity of PET for whole body imaging by targeting molecular features amplified in lesions. ImmunoPET probes targeting different antigens and their utility to measure response to treatment were explored. 89Zr-trastuzumab was employed as a surrogate readout of Src inhibition after …

Noninvasive Multimodal Diffuse Optical Imaging Of Vulnerable Tissue Hemodynamics, Mingjun Zhao

Theses and Dissertations--Biomedical Engineering

Measurement of tissue hemodynamics provides vital information for the assessment of tissue viability. This thesis reports three noninvasive near-infrared diffuse optical systems for spectroscopic measurements and tomographic imaging of tissue hemodynamics in vulnerable tissues with the goal of disease diagnosis and treatment monitoring. A hybrid near-infrared spectroscopy/diffuse correlation spectroscopy (NIRS/DCS) instrument with a contact fiber-optic probe was developed and utilized for simultaneous and continuous monitoring of blood flow (BF), blood oxygenation, and oxidative metabolism in exercising gastrocnemius. Results measured by the hybrid NIRS/DCS instrument in 37 subjects (mean age: 67 ± 6) indicated that vitamin D supplement plus aerobic training …