Biomedical Engineering and Bioengineering Commons^™

Longitudinal Case-Control Study Of Mammographic Breast Tissue Subtypes, Kendra Batchelder

Electronic Theses and Dissertations

Breast density is a known risk factor for breast cancer. However, there has been limited research on potential subtypes of mammographic dense breast tissue to identify areas of active dense tissue that is structurally reorganizing and links to cancer dynamics, versus areas of passive dense tissue which remains organized. We hypothesize that the amounts of subtypes of mammographic dense tissue and the associated rate of change through time could provide insights into breast cancer risk. A retrospective study was conducted to investigate breast cancer using longitudinal screening mammograms and accompanying pathology reports collected in 2015. Patients were matched by age …

Hybrid Power Spectral And Wavelet Image Roughness Analysis, Basel White

Electronic Theses and Dissertations

The Two-Dimensional Wavelet Transform Modulus Maxima (2D WTMM) sliding window methodology has proven to be a robust approach, in particular for the extraction of the Hurst (H) roughness exponent from grayscale mammograms. The power spectrum is a computational analysis based on the Fourier transform that can be used to estimate the roughness of a scale-invariant image or region via the calculation of H. We aim to examine how the calculation of H in fractional Brownian motion (fBm) images and mammograms can be improved. fBm images are generated for H ∈ [0.00,1.00] for testing through the previous 2D …

Mechanical Design Of A Microwave Imaging Device For Breast Cancer Detection In Mri Scanners, Grace M. Player

Dartmouth College Master’s Theses

This project seeks to develop an updated version of a microwave imaging device for use in conjunction with breast MRI, improving upon existing technology and developing novel concepts for the device. It posits three primary redesign targets for updating the previous system: resizing the system height, making the device more iteration- friendly, and improving the overall manufacturability of the device by replacing custom components with commercially available alternatives. All three of these redesign targets are met in the new design, V2.0. The height is reduced by reducing antenna travel and height, embedding some components, and shortening the tank wall, resulting …

Impacts Of Diverse Inflammatory Stimuli On Neutrophil Behavior: Extracellular Vesicles, E-Cigarettes, And Nanoparticles, Hunter T. Snoderly

Graduate Theses, Dissertations, and Problem Reports

Neutrophils are the body’s front-line defenders against foreign insult and are key players in a variety of inflammatory conditions. This body of work examines the role of neutrophils in promoting pathology in three distinct inflammatory contexts. In the pro-inflammatory state provoked by breast cancer, neutrophils decondense their nuclei and release cytotoxic web-like structures known as neutrophil extracellular traps (NETs). NETs form most commonly via histone modifications facilitated by the enzyme PAD4. NETs are known to be a harbinger of disease progression and promote metastasis through capture of circulating tumor cells. It was hypothesized that breast tumors release small particles known …

Determination Of Tissue-Level Changes In Tumors That Are Indicative Of Metastasis Using Optical Spectroscopy, Sanidhya D. Tripathi

Biomedical Engineering Undergraduate Honors Theses

Breast cancer, accounting for 12% of all new cancer cases, is one of the leading causes of death in women worldwide. Although patient survival has improved over the years, metastatic spread to other organ sites and not due to the primary tumor is the most common form of tumor recurrence, accounting for 90% deaths. Hypoxia is a common hallmark of solid tumors and is linked with metastasis, therapeutic resistance, and poor patient survival. Defined as a state of decreased oxygen availability, cells under hypoxia have an increased rate of genetic mutation, local invasion, and resistance to treatment such as radiation …

Characterizing Mechanical Regulation Of Bone Metastatic Breast Cancer Cells, Boyuan Liu

Doctoral Dissertations

Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical stimuli in the skeleton are an important microenvironmental parameter that modulates tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. This work focused on bone matrix deformation and interstitial fluid flow based on their well-known roles in bone remodeling and in primary breast cancer. The goal of our research was to establish a platform that could define the relationship between …

Advancing Combined Radiological And Optical Scanning For Breast-Conserving Surgery Margin Guidance, Samuel Stewart Streeter

Dartmouth College Ph.D Dissertations

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to …

Development Of Quantitative Molecular Photoacoustic Imaging For Noninvasive Cancer Diagnostics, Cayla Zandbergen

Dissertations & Theses (Open Access)

Traditional diagnostic imaging provides clinicians with anatomical information that guides both diagnosis and treatment planning; however, once a tumor has progressed enough to be visible, it has often reached an advanced stage. Molecular imaging techniques allow for real-time visualization of chemical and biological processes via imaging of specific biomarkers, which can facilitate detection of malignancies before they become visible. One biomarker of interest is blood oxygen saturation (SO₂) due to its correlation with hypoxia, which is associated with increased tumor malignancy; some studies have also established SO₂ as an independent biomarker of disease progression. Additionally, because cancerous …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Detection Methods And Clinical Applications Of Circulating Tumor Cells In Breast Cancer, Hongyi Zhang, Xiaoyan Lin, Yuan Huang, Minghong Wang, Chunmei Cen, Shasha Tang, Marcia R. Dique, Lu Cai, Manuel A. Luis, Jillian Smollar, Yuan Wan, Fengfeng Cai

Publications and Research

Circulating Tumor Cells (CTCs) are cancer cells that split away from the primary tumor and appear in the circulatory system as singular units or clusters, which was first reported by Dr. Thomas Ashworth in 1869. CTCs migrate and implantation occurs at a new site, in a process commonly known as tumor metastasis. In the case of breast cancer, the tumor cells often migrate into locations such as the lungs, brain, and bones, even during the early stages, and this is a notable characteristic of breast cancer. Survival rates have increased significantly over the past few decades because of progress made …

The Age-Dependent Characterization Of The Er-Alpha Positive Breast Cancer Tumor Microenvironment, Katie Marie Hamel

LSU Doctoral Dissertations

In disease states such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression and drug resistance. Young individuals diagnosed with estrogen receptor-alpha positive (ER-a+) breast cancer have an observed increase in resistance to endocrine therapies. This suggests that an alternative estrogen signaling pathway is active within these tumors. Despite this, the effects of stromal age on the endocrine response in breast cancer is not well known. Here, we review and highlight the involvement of the stromal age in both tumorigenesis and physiological wound healing. To identify specific differences between young and aged ER-a+ breast tumors, RNA …

Characterizing The Biophysical Properties And Origin Of Extracellular Matrix In The Breast Tumor Microenvironment, Connor T. King

LSU Master's Theses

Tumors derived from breast tissue possess the ability to manipulate and permanently alter their surrounding tissue. Studies demonstrate that tissues surrounding breast tumors have differences in secreted factors as well as extracellular matrix (ECM) deposition and structure. However, some fundamental gaps exist within this paradigm: specifically, what exacerbates this transformation and are these changes maintained between the subtypes of breast tumors? Therefore, a targeted evaluation of the effects of the tumor on the stromal microenvironment in a subtype specific manner will be invaluable. To determine if tumor aggressiveness and subtype differentially regulate the tumor microenvironment, a model must be constructed …

Cis-Resveratrol Upregulates Tyrosyl-Trna Synthetase And Inhibits The Proliferation Of Select Breast Cancer Cell Lines, Marion Cone Hope Iii

Theses and Dissertations

Breast cancer is one of the most commonly occurring cancers in women. 70% of breast cancer patients express ERα and are treated with tamoxifen (Tam), a drug that is used to directly target ERα. However, 20-30% of cancer patients develop a resistance to Tam. This resistance leads to a worse prognosis and other treatments such as DNA damaging drugs or radiation to eliminate these cells. Resveratrol (RSV) is a polyphenolic- compound found in plants such as grapes and hellebore and is known to evoke anti-cancer effects. While natural resveratrol exists as a mixture of both cis- and trans- isomers, so …

Engineered Three-Dimensional Scaffolds Modulating Fate Of Breast Cancer Cells Using Stiffness And Morphology Related Cell Adhesion, Samerender Nagam Hanumantharao, Carolynn Que, Brennan Vogl, Smitha Rao

Michigan Tech Publications

Goal: Artificially engineering the tumor microenvironment in vitro as a vital tool for understanding the mechanism of tumor progression. In this study, we developed three-dimensional cell scaffold systems with different topographical features and mechanical properties but similar surface chemistry. The cell behavior was modulated by the topography and mechanical properties of the scaffold. Adenocarcinoma (MCF7), triple-negative (MDA-MB-231) and premalignant (MCF10AneoT) breast cancer cells were seeded on the scaffold systems. The cell viability, cell-cell interaction and cell-matrix interactions were analyzed. The preferential growth and alignment of specific population of cells were demonstrated. Among the different scaffolds, triple-negative breast cancer cells preferred …

Electrospun Nanofiber Scaffolds As A Platform For Breast Cancer Research, Carolynn Que

Dissertations, Master's Theses and Master's Reports

Tumorigenesis is a complex process involving numerous cellular signaling cascades and environmental factors. Here, we report the fabrication of 3D scaffolds with different morphologies obtained by to study cancer cell proliferation and migration. Using an FDA approved, biocompatible and biodegradable polymer Polycaprolactone (PCL), we electrospun nanofiber scaffolds having mesh, aligned, and honeycomb morphologies. The role of the morphology and cellular preferences to nutrition in cell adhesion and proliferation was assessed using scaffolds obtained by electrospinning PCL with fluorescent fructose-like molecular probes. Cell viability, cell morphology, localized cellular growth as related to scaffold morphology and availability of the fructose-like molecular probes …

Using Feature Extraction From Deep Convolutional Neural Networks For Pathological Image Analysis And Its Visual Interpretability, Wei-Wen Hsu

Electrical & Computer Engineering Theses & Dissertations

This dissertation presents a computer-aided diagnosis (CAD) system using deep learning approaches for lesion detection and classification on whole-slide images (WSIs) with breast cancer. The deep features being distinguishing in classification from the convolutional neural networks (CNN) are demonstrated in this study to provide comprehensive interpretability for the proposed CAD system using the domain knowledge in pathology. In the experiment, a total of 186 slides of WSIs were collected and classified into three categories: Non-Carcinoma, Ductal Carcinoma in Situ (DCIS), and Invasive Ductal Carcinoma (IDC). Instead of conducting pixel-wise classification (segmentation) into three classes directly, a hierarchical framework with the …

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 …

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 …

Acetylation Profiles Of Histone And Non-Histone Proteins In Breast Cancer, Alla Karpova

McKelvey School of Engineering Theses & Dissertations

This study evaluates the impact of protein acetylation on breast cancer gene expression and the regulation of metabolism. Acetylation is the second abundant post-translational modification after phosphorylation, regulating protein activity and function. The alterations in acetylation of both histone and non-histone proteins is known to be related to many human diseases, including cancer. Acetylation and deacetylation of histones is closely associated with the regulation of gene expression, while acetylation of non-histone proteins may have a broad effect on major cellular processes, such as proliferation, metabolism, cell cycle and apoptosis, imbalanced regulation of which is essential for cancer development. Therefore, it’s …

Tissue Oxygen Saturation Predicts Response To Breast Cancer Neoadjuvant Chemotherapy Within 10 Days Of Treatment, Jeffrey M. Cochran, David R. Busch, Anais Leproux, Zheng Zhang, Thomas D. O'Sullivan, Albert E. Cerussi, Philip M. Carpenter, Rita S. Mehta, Darren Roblyer, Wei Yang, Keith D. Paulsen, Brian Pogue, Shudong Jiang, Peter A. Kaufman

Dartmouth Scholarship

Ideally, neoadjuvant chemotherapy (NAC) assessment should predict pathologic complete response (pCR), a surrogate clinical endpoint for 5-year survival, as early as possible during typical 3- to 6-month breast cancer treatments. We introduce and demonstrate an approach for predicting pCR within 10 days of initiating NAC. The method uses a bedside diffuse optical spectroscopic imaging (DOSI) technology and logistic regression modeling. Tumor and normal tissue physiological properties were measured longitudinally throughout the course of NAC in 33 patients enrolled in the American College of Radiology Imaging Network multicenter breast cancer DOSI trial (ACRIN-6691). An image analysis scheme, employing z-score normalization to …

Turning Up Antitumor Immunity Against Breast Cancer, Johnie Hodge

Theses and Dissertations

Breast cancer is the most common cancer in women worldwide, and is the second leading cause of cancer-related death in spite of significant advances in treatment and emphasis on early diagnosis. While treatment of localized disease is often successful, metastatic breast cancer, especially of the triple negative molecular subtype, carries a much poorer prognosis. The significant role of the immune system in the progression from localized to metastatic disease is becoming more and more appreciated. Tumor escape from immune surveillance and immune suppression in the tumor microenvironment have become therapeutic targets in addition to the traditional goals of directly killing …

Magnetically Actuated Cell Stretching Platform To Induce Phenotypic Changes In Metastatic Cells, Yong Gyun Cho, Hyunsu Park, Hyowon Lee, Sarah Libring

The Summer Undergraduate Research Fellowship (SURF) Symposium

Although metastasis is responsible for about 90% of cancer deaths, only few in vitro models can be used to evaluate dynamic behaviors of metastatic cancer cells. Many studies have shown that mechanical stimuli can trigger various cellular responses such as gene and protein expression, which could lead to changes in cellular phenotype. Similarly, metastasized breast cancer cells in the lung tissue are constantly stretched by cyclic mechanical stress due to breathing, which alters cellular morphology and proliferation state. Such transitions can make the secondary tumors resistant to the chemotherapy used to effectively treat the primary tumors. In this work, we …

Metabolism-Driven High-Throughput Cancer Identification With Glut5-Specific Molecular Probes, Srinivas Kannan, Vagarshak Begoyan, Joseph Fedie, Shuai Xia, Łukasz J. Weseliński, Marina Tanasova, Smitha Rao

Michigan Tech Publications

Point-of-care applications rely on biomedical sensors to enable rapid detection with high sensitivity and selectivity. Despite advances in sensor development, there are challenges in cancer diagnostics. Detection of biomarkers, cell receptors, circulating tumor cells, gene identification, and fluorescent tagging are time-consuming due to the sample preparation and response time involved. Here, we present a novel approach to target the enhanced metabolism in breast cancers for rapid detection using fluorescent imaging. Fluorescent analogs of fructose target the fructose-specific transporter GLUT5 in breast cancers and have limited to no response from normal cells. These analogs demonstrate a marked difference in adenocarcinoma and …

3d Bioprinting Systems For The Study Of Mammary Development And Tumorigenesis, John Reid

Electrical & Computer Engineering Theses & Dissertations

Understanding the microenvironmental factors that control cell function, differentiation, and stem cell renewal represent the forefront of developmental and cancer biology. To accurately recreate and model these dynamic interactions in vitro requires both precision-controlled deposition of multiple cell types and well-defined three-dimensional (3D) extracellular matrix (ECM). To achieve this goal, we hypothesized that accessible bioprinting technology would eliminate the experimental inconsistency and random cell-organoid formation associated with manual cell-matrix embedding techniques commonly used for 3D, in vitro cell cultures. The first objective of this study was to adapt a commercially-available, 3D printer into a 3D bioprinter. Goal-based computer simulations were …

Nanopulse Stimulation (Nps) Induces Tumor Ablation And Immunity In Orthotopic 4t1 Mouse Breast Cancer: A Review, Stephen J. Beebe, Brittany P. Lassiter, Siqi Guo

Bioelectrics Publications

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Computer-Aided Cancer Diagnosis And Grading Via Sparse Directional Image Representations, Hadi Rezaeilouyeh

Electronic Theses and Dissertations

Prostate cancer and breast cancer are the second cause of death among cancers in males and females, respectively. If not diagnosed, prostate and breast cancers can spread and metastasize to other organs and bones and make it impossible for treatment. Hence, early diagnosis of cancer is vital for patient survival. Histopathological evaluation of the tissue is used for cancer diagnosis. The tissue is taken during biopsies and stained using hematoxylin and eosin (H&E) stain. Then a pathologist looks for abnormal changes in the tissue to diagnose and grade the cancer. This process can be time-consuming and subjective. A reliable and …

Dysregulation Of Phospholipase D (Pld) Isoforms Increases Breast Cancer Cell Invasion, Kristen Fite

Browse all Theses and Dissertations

Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor under various stressors will promote phenotypic cellular changes, known as epithelial-to-mesenchymal transition (EMT), which allows cells to begin to invade surrounding tissue, enter the circulatory system, and eventually seed a distant metastatic site. The phospholipase D (PLD) enzymes are critical regulators of cell signaling pathways necessary for cell migration. While the importance of PLD enzymes in cancer cell invasion is well known, clinically applicable methods of PLD inhibition are not yet available. The best-studied isoforms …

Tumor-Microenvironment-On-Chip To Mimic Tumor Heterogeneity, Victoria Noe-Kim, Altug Ozcelikkale, Bumsoo Han

The Summer Undergraduate Research Fellowship (SURF) Symposium

Ductal Carcinoma In Situ (DCIS) is a non-invasive cancer that forms around breast milk ducts that can potentially progress into invasive breast cancer if untreated. Lack of models to study its diverse pathophysiology and differential response to treatments poses a challenge to develop standard treatment modalities with improved therapeutic outcomes. The traditional in vitro models such as cell monolayer are convenient but insufficient to represent the physiological characteristics of DCIS tumor microenvironment and often fail to predict clinical outcomes. The animal models effectively simulate the in vivo environment but also lack the ability to control the environmental parameters to match …

Field Penetration In Mri-Based Breast Models: A Numerical Investigation, Giuseppe Ruvio, Raffaele Solimene, Antonio Cuccaro, Max Ammann

Articles

The use of reliable computational tools is fundamental to investigate different aspects of microwave breast cancer imaging. From the development of high-definition and realistic numerical breast models, different coupling mechanisms and the reaction of different tissues to microwave signals can be characterized. In this paper, field penetration inside four numerical breast phantoms with varying adipose content is evaluated in the frequency range 0.5 - 10 GHz across sagittal cuts.