Bioimaging and Biomedical Optics Commons^™

Tissue Clearing As A Mechanism To Identify Changes In Fibronectin Structure During Breast Cancer Metastasis, Maryam Nuru, Kelsey Hopkins, Luis Solorio

The Summer Undergraduate Research Fellowship (SURF) Symposium

With metastasis accounting for approximately 90% of breast cancer deaths and an alarming number of over 300,000 new breast cancer cases to be diagnosed by the end of 2018, there is growing need to understand the process of breast cancer. Changes in the extracellular matrix (ECM) of the tumor microenvironment play an essential role in this deadly tumor progression. Specifically, the glycoprotein fibronectin (FN), has been identified to be up-regulated in patients with worse clinical outcomes. During tumor progression fibronectin undergoes conformational changes that aid in metastatic dissemination. In order to analyze the dynamic changes in FN expression and evaluate …

Super‐Resolution Imaging Of Amyloid Structures Over Extended Times By Using Transient Binding Of Single Thioflavin T Molecules, Kevin Spehar, Tianben Ding, Yuanzi Sun, Niraja Kedia, Jin Lu, George R. Nahass, Matthew D. Lew, Jan Bieschke

Electrical & Systems Engineering Publications and Presentations

Oligomeric amyloid structures are crucial therapeutic targets in Alzheimer's and other amyloid diseases. However, these oligomers are too small to be resolved by standard light microscopy. We have developed a simple and versatile tool to image amyloid structures by using thioflavin T without the need for covalent labeling or immunostaining. The dynamic binding of single dye molecules generates photon bursts that are used for fluorophore localization on a nanometer scale. Thus, photobleaching cannot degrade image quality, allowing for extended observation times. Super‐resolution transient amyloid binding microscopy promises to directly image native amyloid by using standard probes and record amyloid dynamics …

A Study Of Acoustically Activated Nanodroplets, Songita Choudhury

Theses & Dissertations

Current treatment of acute myocardial infarction (AMI), which is the main pathophysiological event leading to death in the United States, has advanced considerably with the introduction of emergent percutaneous interventions, but there remains an urgent need for novel techniques to rapidly and accurately detect infarcted or ischemic tissue that results from AMI. Ultrasound contrast agents, also known as microbubbles (MB), have become commonplace in echocardiography. However, MBs are purely intravascular tracers and unable to cross endothelial barriers due to size. The limitations of MBs, namely size and short circulation times within the human body, led to the development of phase-change …

Quantification Of Tumor-Associated Macrophages Following Immunomodulation Therapy In A Murine Allograft Model Of Colorectal Carcinoma, Caroline Spainhour

Biomedical Engineering Undergraduate Honors Theses

Colorectal Carcinoma (CRC) is one of the deadliest cancers in the world, with 150,000 new cases annually in the United States. Traditional treatments include chemotherapy and invasive surgery; however, research has shown that only 25% of patients that undergo traditional treatment have a positive result. Immunotherapy is an emerging form of cancer treatment that utilizes the patients’immune system to fight cancer cells by targeting inflammation, which plays a large role in the proliferation and metastasis of cancer cells.

Tumor-associated macrophages (TAMs) are immune cells that affect the inflammatory microenvironment of tumors. TAMs are M1 in the early stages of tumors, …

Renal Granulomatosis Post Intravesical Bacillus Calmette-Guerin Therapy For Non-Muscle-Invasive Bladder Cancer, Karen Tran-Harding, Rashmi T. Nair, Halemane S. Ganesh

Radiology Faculty Publications

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in < 5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

Optical Coherence Tomography Application To Alopecia In The Scalp, Elizabeth Melcher

Research Opportunities for Engineering Undergraduates (ROEU) Program 2017-18

Alopecia is the loss of hair, whether it be from the scalp or other regions of the body. Current techniques used to best diagnose and track alopecia are often invasive, requiring a biopsy for results. The use of the OCT, or optical coherence tomography, could drastically improve a patient’s experience in undergoing a diagnosis while proving accurate results. The objective of this study is to develop diagnostic algorithms for the rapid, non-invasive diagnosis of alopecia with OCT. The first step is collecting OCT images of a healthy scalp to understand the anatomical structures with the imaging technique.

Optical Imaging Of Metabolic Adaptability As A Biomarker For Metastatic Potential In Breast Cancer Cells, Mason G. Harper

Biomedical Engineering Undergraduate Honors Theses

Breast cancer metastasis is the main cause for mortality in breast cancer patients. However, knowledge of metastatic recurrence is limited, and there is a need to understand metastatic recurrence in order to treat breast cancer patients more effectively. Highly invasive metastatic breast cancer has shown to exhibit metabolic adaptability, transitioning from glycolysis to oxidative phosphorylation in the presence of microenvironmental stress. NADH and FAD are naturally occurring cofactor products during glycolysis and oxidative phosphorylation, respectively, and they are of particular importance during these metabolic processes due to their endogenous fluorescence. Measuring the ratio of fluorescence intensities of these cofactors through …

Detection Of Leukocytes Stained With Acridine Orange Using Unique Spectral Features Acquired From An Image-Based Spectrometer, Courtney J. Hunter

Biomedical Engineering Undergraduate Honors Theses

A leukocyte differential count can be used to diagnosis a myriad blood disorders, such as infections, allergies, and efficacy of disease treatments. In recent years, attention has been focused on developing point-of-care (POC) systems to provide this test in global health settings. Acridine orange (AO) is an amphipathic, vital dye that intercalates leukocyte nucleic acids and acidic vesicles. It has been utilized by POC systems to identify the three main leukocyte subtypes: granulocytes, monocytes, and lymphocytes. Subtypes of leukocytes can be characterized using a fluorescence microscope, where the AO has a 450 nm excitation wavelength and has two peak emission …

A Novel Hybrid Imaging System To Aid In Surgical Decision Making, Lawrence Yip, Madeleine Van De Kleut, Ivan Kosik, Astrid Chamson-Reig, Jeffrey Jl Carson

Western Research Forum

Background:

Breast cancer accounts for 25% of all cancer cases among women. In breast-conserving surgery, a common treatment, the tumour is excised with a healthy tissue margin. However, detection of the margin can be difficult. Current techniques to guide excision are often insufficient, and re-excision can occur up to 25% of the time.

Methods:

Photoacoustic imaging is a hybrid imaging modality that combines the advantages of optical imaging and ultrasound while using safe non-ionizing light. This project involves the development of a novel imaging system with a new scanner design to overcome common limitations and provide images to aid in …

Engineering Fret Biosensors For Microrna Presence/Absence Analysis, Nicholas E. Larkey, Sean M. Burrows

Biomedical Engineering Western Regional Conference

No abstract provided.

Utility Of Ultrasound/Photoacoustic Imaging For Accurate Catheter Tracking And Temperature Monitoring During Endovenous Laser Ablation, Ayushi Jharia, Keerthana Palani, Yan Yan

Research Opportunities for Engineering Undergraduates (ROEU) Program 2016-17

Laser ablation is a treatment method that uses light energy through a catheter inserted into a vein to induce localized heat to close the diseased blood vessels. Ultrasound (US) imaging has been used for catheter visualization and tracking. US has limitations for tracking the accurate location of the fiber tip inside small perforating veins such as angular dependency and comet tail artifacts. We propose a robust and accurate method for fiber tip tracking using combined US and Photoacoustic (PA) imaging to overcome the existing limitations.

Biventricular Finite Element Modeling And Quantification Of 3d Langragian Strains And Torsion Using Dense Mri, Zhanqiu Liu

Theses and Dissertations--Mechanical and Aerospace Engineering

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in …

Feasibility Of Using Raman-Based Techniques For Breast Cancer Detection, Sara Mollamohammada

Department of Civil and Environmental Engineering: Dissertations, Theses, and Student Research

Breast cancer is one of the common types of cancer among women all over the world. Early diagnosis is an effective way that improve the treatment process and gives the patients a better chance of survival. Many of the patients infected by breast cancer choose breast conservation surgery (BCS). However, some of those will be subjected to mastectomy, and many will have tumor recurrence as there is no precise technique to show the tumor margins. Raman-based methods are powerful techniques with potential to rapidly differentiate normal from tumor tissues and provides a solution to detect tumor margin. This is because …

Improved Sensitivity To Fluorescence For Cancer Detection In Wide-Field Image-Guided Neurosurgery, Michael Jermyn, Yoann Gosselin, Pablo A. Valdes, Mira Sibai, Kolbein Kolste

Dartmouth Scholarship

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

Review Of Fluorescence Guided Surgery Visualization And Overlay Techniques, Jonathan T. Elliott, Alisha V. Dsouza, Scott C. Davis, Jonathan D. Olson, Keith Paulsen, David Roberts, Brian Pogue

Dartmouth Scholarship

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check.

Review Of Biomedical Čerenkov Luminescence Imaging Applications, Kaveh Tanha, Ali Mahmoud Pashazadeh, Brian W. Pogue

Dartmouth Scholarship

Čerenkov radiation is a fascinating optical signal, which has been exploited for unique diagnostic biological sensing and imaging, with significantly expanded use just in the last half decade. Čerenkov Luminescence Imaging (CLI) has desirable capabilities for niche applications, using specially designed measurement systems that report on radiation distributions, radiotracer and nanoparticle concentrations, and are directly applied to procedures such as medicine assessment, endoscopy, surgery, quality assurance and dosimetry. When compared to the other imaging tools such as PET and SPECT, CLI can have the key advantage of lower cost, higher throughput and lower imaging time. CLI can also provide imaging …

Next-Generation Raman Tomography Instrument For Non-Invasive In Vivo Bone Imaging, Jennifer-Lynn H. Demers, Francis W. L. Esmonde-White, Karen A. Esmonde-White, Michael D. Morris, Brian Pogue

Dartmouth Scholarship

Combining diffuse optical tomography methods with Raman spectroscopy of tissue provides the ability for in vivo measurements of chemical and molecular characteristics, which have the potential for being useful in diagnostic imaging. In this study a system for Raman tomography was developed and tested. A third generation microCT coupled system was developed to combine 10 detection fibers and 5 excitation fibers with laser line filtering and a Cytop reference signal. Phantom measurements of hydroxyapatite concentrations from 50 to 300 mg/ml had a linear response. Fiber placement and experiment design was optimized using cadaver animals with live animal measurements acquired to …

Noncontact Diffuse Correlation Tomography Of Breast Tumor, Lian He

Theses and Dissertations--Biomedical Engineering

Since aggressive cancers are frequently hypermetabolic with angiogenic vessels, quantification of blood flow (BF) can be vital for cancer diagnosis. Our laboratory has developed a noncontact diffuse correlation tomography (ncDCT) system for 3-D imaging of BF distribution in deep tissues (up to centimeters). The ncDCT system employs two sets of optical lenses to project source and detector fibers respectively onto the tissue surface, and applies finite element framework to model light transportation in complex tissue geometries. This thesis reports our first step to adapt the ncDCT system for 3-D imaging of BF contrasts in human breast tumors. A commercial 3-D …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

Quantitative Spatial Frequency Fluorescence Imaging In The Sub-Diffusive Domain For Image-Guided Glioma Resection, Mira Sibai, Israel Veilleux, Jonathan T. Elliott, Frederic Leblond, Brian Wilson

Dartmouth Scholarship

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue.

Femtosecond Laser Beam Propagation Through Corneal Tissue: Evaluation Of Therapeutic Laser-Stimulated Second And Third-Harmonic Generation, William R. Calhoun Iii

Theses and Dissertations

One of the most recent advancements in laser technology is the development of ultrashort pulsed femtosecond lasers (FSLs). FSLs are improving many fields due to their unique extreme precision, low energy and ablation characteristics. In the area of laser medicine, ophthalmic surgeries have seen very promising developments. Some of the most commonly performed surgical operations in the world, including laser-assisted in-situ keratomileusis (LASIK), lens replacement (cataract surgery), and keratoplasty (cornea transplant), now employ FSLs for their unique abilities that lead to improved clinical outcome and patient satisfaction.

The application of FSLs in medical therapeutics is a recent development, and although …

Nerve Fiber Diameter Measurements Using Hematoxylin And Eosin Staining And Brightfield Microscopy To Assess The Novel Method Of Characterizing Peripheral Nerve Fiber Distributions By Group Delay, Jorge Arturo Vazquez

Master's Theses

Peripheral neuropathies are a set of common diseases that affect the peripheral nervous system, causing damage to vital connections between various parts of the body and the brain and spinal cord. Different clinical conditions are known to selectively impact various size nerve fibers, which often makes it difficult to diagnose which peripheral neuropathy a patient might have. The nerve conduction velocity diagnostic test provides clinically useful information in the diagnosis of some peripheral neuropathies. This method is advantageous because it tends to be minimally invasive yet it provides valuable diagnostic information. However, this test does not determine characteristics of peripheral …

Fluid Powered Miniature In Vivo Robots For Minimally Invasive Surgery (Mis), Abolfazl Pourghodrat

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Minimizing the invasiveness of surgery is believed to improve patient outcomes. Bleeding, infection, and pain are major concerns in surgery afflicting patients for decades. Minimally invasive techniques have come into play to reduce these concerns and smooth the evolution of abdominal surgery to a scarless process where nearly all surgeries can be performed without a skin incision. Technology continually advances the frontier of development of novel surgical devices to implement less invasive surgical techniques.

Fusion of robotics and Minimally Invasive Surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …

Spectral Discrimination Of Breast Pathologies In Situ Using Spatial Frequency Domain Imaging, Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, David J. Cuccia, Bruce J. Tromberg, Keith D. Paulsen, Brian W. Pogue, Wendy A. Wells

Dartmouth Scholarship

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Fluorescence Characterization Of Quantum Dots For Use As Biomarkers, Logan M. Grimes

Materials Engineering

Fluorescence profiles of quantum dots (QDs) were characterized to select the ideal QDs for encapsulation in phospholipids for use as biomarkers to selectively adhere to cancer cells. QDs were synthesized and extracted 0, 30, 60, and 90 seconds after precursor compounds were mixed. These extractions were isolated by extraction time. Portions from each vial were coated in a zinc sulfide shelling procedure, leaving at least half of the QD solution unshelled. These samples were characterized over four days to monitor fluctuations in fluorescence. This was done utilizing an Ocean Optics spectrometer in conjunction with Spectra Suite software. The central wavelength, …

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

Biomedical Photoacoustic Imaging Using Gas-Coupled Laser Acoustic Detection, Jami Johnson

Student Research Initiative

Several detection methods have been explored for photoacoustic and ultrasound imaging of biological tissues. Piezoelectric transducers are commonly used, which require contact with the sample to be imaged and have limiting bandwidth characteristics. Interferometry detection exhibits improved bandwidth characteristics and resolution, yet generally require complicated optics and the incorporation of a contacting reflective medium. In this paper, we report the use of a noncontact photoacoustic imaging system that does not require the use of a reflective layer. A simple, robust technique known as gas-coupled laser acoustic detection is used, which has previously been applied to evaluation of composite materials. This …

Scanning In Situ Spectroscopy Pplatform For Imaging Surgical Breast Tissue Specimens, Venkataramanan Krishnaswamy, Ashley M. Laughney, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

A non-contact localized spectroscopic imaging platform has been developed and optimized to scan 1 x 1 cm² square regions of surgically resected breast tissue specimens with ~150-micron resolution. A color corrected, image-space telecentric scanning design maintained a consistent sampling geometry and uniform spot size across the entire imaging field. Theoretical modeling in ZEMAX allowed estimation of the spot size, which is equal at both the center and extreme positions of the field with ~5% variation across the designed waveband, indicating excellent color correction. The spot sizes at the center and an extreme field position were also measured experimentally using the …