Bioimaging and Biomedical Optics Commons^™

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 …

Real-Time Navigation System For Breast Cancer Surgery With Pre- And Intra-Operative Imaging Using Neural Networks, Motaz Alqaoud

Biomedical Engineering Theses & Dissertations

Breast cancer is one of the most frequently diagnosed malignancies in women worldwide, necessitating precise diagnosis and treatment. Breast-conserving surgery (BCS) is the primary treatment for nonpalpable cases, yet current approaches often lack accuracy due to the absence of real-time 3D imaging during surgery. This limitation impairs surgeons’ ability to visualize tumor locations, compromising outcomes and potentially leading to repeat surgeries with higher risks, undesirable cosmetic results, increased costs, and, in some cases, mastectomy. Thus, there is a critical need for a navigation system to facilitate accurate tumor excision in nonpalpable breast cancer through real-time patient-specific 3D tracking.

This study …

Nanoparticles For Applications In Specific Diagnostics And Precision Medicine, Naxhije Berisha

Dissertations, Theses, and Capstone Projects

Heterogeneity is common in the expression of cancer and treatment response. Precision medicine enables healthcare providers to tailor medical care to an individual's distinct genetic and environmental makeup. This customization has the potential to result in more efficient treatments while minimizing side effects. We believe that by studying the interface of nanotechnology and cancer medicine we can elucidate innovative solutions that address the challenges of disease heterogeneity. This includes advancements in drug delivery, formulations development, and diagnostic sensing. We highlight three studies that use nanotechnology for applications in precision medicine. In Chapter 2, we highlight design optimization of drug formulations …

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

Graduate Theses and Dissertations (2019 - present)

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …

Labeling Melanoma Cells With Black Microspheres For Improved Sensitivity In Detection Via Photoacoustic Flow Cytometry, Tori Kocsis

Electronic Theses and Dissertations

Melanoma is an aggressive form of skin cancer known for developing into metastatic disease. Current clinical diagnostics, including medical imaging and tissue biopsy, provide a poor prognosis since the cancer is in the late stages of disease progression. In recent years, photoacoustic flow cytometry has allowed for the detection of circulating melanoma cells within patient blood samples in vitro. Although this method exploits the naturally-produced melanin within the cells, it has only successfully detected highly-pigmented melanoma cell lines. Since various forms of melanoma exist, each with varying melanin concentrations, this research aims to provide a novel method for detecting lightly-pigmented …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Artificial Image Objects For Classification Of Breast Cancer Biomarkers With Transcriptome Sequencing Data And Convolutional Neural Network Algorithms, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin M. Balko, Jingchun Chen

School of Medicine Faculty Research

Background: Transcriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively for clinical applications due to the high dimension of the data and the highly correlated expression between individual genes. Methods: We proposed a method to transform RNA sequencing data into artificial image objects (AIOs) and applied convolutional neural network (CNN) algorithms to classify these AIOs. With the AIO technique, we considered each gene as a pixel in an image and its expression level as pixel intensity. Using the GSE96058 (n = 2976), GSE81538 (n = 405), and GSE163882 (n = …

Deep Learning-Based Breast Cancer Detection And Classification Using Histopathology Images, Ghulam Murtaza

Student Works (2020-2029)

Cancer disease is drastically increasing worldwide over the past few years. Among all types of cancers in women, breast cancer (BrC) is the main cause of abnormal deaths. For a confident diagnosis of BrC, histopathology (Hp) images are usually suggested by the doctors. BrC detection is a diagnostic test for benign (non-cancerous) and malignant (cancerous) breast tumors (BrT). Once the BrT is diagnosed, then it needs to be classified for subtypes of benign and malignant to start specific treatment. Several studies developed BrC detection and classification models using Hp images. However, the existing models required high computational resources, long training …

Understanding Radiation Resistance In Head And Neck Tumor Xenografts Using Diffuse Reflectance And Raman Spectroscopy, Sina Dadgar

Graduate Theses and Dissertations

Each year, 800,000 new patients are diagnosed with head and neck squamous cell carcinoma (HNSCC), a majority of whom are treated with a combination of daily fractions of radiation and weekly chemotherapy sessions for up to seven weeks. Current methods to evaluate treatment response of individual patients are limited to anatomical measurements of tumor burden using CT scan or MRI 4-8 weeks after completion of treatment. However, earlier knowledge of radiation-response prior to or at early days after commencement of therapy can aid oncologist with escalating and de-escalating treatment plans for exceptionally non-responding and responding patients. Such a knowledge can …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

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 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 …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price

Wayne State University Dissertations

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.

Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.

A 36×43×2 cm3 phantom with 255 known landmarks …

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 …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …

A Review Of Autoimmune Diseases Associated With Cancer, Patricia Tai, Edward Yu, Kurian Joseph, Thomas Miale

Oncology Publications

The focus of this review is on the relationships between autoimmune diseases and cancer from two closely related perspectives: 1.Those autoimmune diseases which are often associated with malignancies. 2.Those prevalent cancers which may increase the risks of developing autoimmune disorders. The review concludes with a brief discussion of some selected innovative approaches to cancer immunotherapy.

Brain Tumor Progression Assessment Using Multiple Mri Volumes, Yufei Shen

Electrical & Computer Engineering Theses & Dissertations

Predicting and assessing tumor progression is important in brain tumor treatment. We attempt to use machine learning techniques to achieve consistency in assessing brain tumor progression. This thesis presents a prediction method of brain tumor progression by exploring a large MR database, which contains two patients ' complete records covering all their visits in the past two years. All ten MRI series, namely, apparent diffusion coefficient (ADC) , diffusion tensor imaging (DTI) , fractional anisotropy (FA), fluid attenuated inversion recovery (FLAIR), max eigenvalue (MAX), mid eigenvalue (MID), min eigenvalue (MIN) , post-contrast T₁-weighted, T₁- weighted, and …

Adjacent Slice Prostate Cancer Prediction To Inform Maldi Imaging Biomarker Analysis, Shao-Hui Chuang

Electrical & Computer Engineering Theses & Dissertations

Prostate cancer is the second most common type of cancer among men in the U.S. [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from …

Robot Assisted Ultrasound Imaged Guided Interstitial Lung Brachytherapy In A Porcine Model, Richard A. Malthaner, Edward Yu, Jerry J. Battista, Chris Blake, Donal Downey, Aaron Fenster

Oncology Presentations

We set out to see if permanent interstitial brachytherapy seeds could be safely and reproducibly inserted thoracoscopicaly with the ZEUS Robotic system and intraoperative ultrasound into in-vivo porcine lungs.

Evaluation Of Intra-And Inter-Fraction Motion In Breast Radiotherapy Using Electronic Portal Imaging Cine Loops, Chrison Lee, Edward Yu, Tomas Kron

Oncology Presentations

Parallel tangent breast irradiation is commonly used postbreast conservation surgery for early breast cancer patient without lymph node involvement to improve local disease control. Intra-fractional and inter-fractional variabilities are often presented in daily treatment setup. The present pilot study used Electronic Portal Imaging (EPI) to evaluate intra-and inter-fraction motion in patients undergoing simple breast tangent radiotherapy.

Implementation Of Gy-Eq For Deterministic Effects Limitation In Shield Design, John W. Wilson, Myung-Hee Y. Kim, Giovanni De Angelis, Francis A. Cucinotta, Nobuaki Yoshizawa, Francis F. Badavi

Mathematics & Statistics Faculty Publications

The NCRP has recently defined RBE values and a new quantity (Gy-Eq) for use in estimation of deterministic effects in space shielding and operations. The NCRP's RBE for neutrons is left ambiguous and not fully defined. In the present report we will suggest a complete definition of neutron RBE consistent with the NCRP recommendations and evaluate attenuation properties of deterministic effects (Gy-Eq) in comparison with other dosimetric quantities.

Is Extended Volume Of External Beam Irradiation Beneficial In Post-Esophagectomy High Risk Patients Receiving Combined Chemoradiation Therapy?, E. Yu, A. R. Dar, R. Ash, G. Videtic, P. Truong, L. Stitt, A. Tomiak, M. Vincent, R. Malthaner, I. Craig, E. Brecevic, W. Kocha, R. Inculet, M. Lefcoe

Oncology Presentations

OBJECTIVE: To assess the value of extended volume irradiation with anastomotic coverage in high risk resected esophageal cancer patients.

METHOD: A retrospective study was undertaken at LRCC from 1989-1999 for high risk resected esophageal cancer patients. Adjuvant treatments consisted of 4 cycles of chemotherapy (epirubicin/fluorouracil/cisplatin or cisplatin/fluorouracil), and local regional irradiation with or without coverage of the anastomotic site. Radiation dose ranged from 45-60Gy at 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage) or small (without anastomotic coverage) field followed by oblique fields for boost.

RESULT: One hundred eighty-eight charts were reviewed. Seventy-two patients were …

Three Dimensional Localization Of Lesions From Digitized Mammograms, Amy L. Magnus

Theses and Dissertations

This thesis describes new algorithms to localize regions-of-interests (ROIs) three dimensionally from a pair of digitized mammograms. This work is intended to add a layer of sophistication to computer aided diagnosis by putting to use the fixed and measurable parameters of mammographic imaging. The fixed parameters are the source to film orientation and the podium-image distance. Measurable parameters are the rotation angle of the x-ray tube from the horizontal and the compression depth (the distance from compression paddle to contact podium distance) at the time of imaging. As an additional benefit, three dimensional localization algorithms alleviate the confusion radiologists may …