A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item Dual-Intended Deep Learning Model for Breast Cancer Diagnosis in Ultrasound Imaging(MDPI, 2022-05-27) Vigil, Nicolle; Barry, Madeline; Amini, Arya; Akhloufi, Moulay; Maldague, Xavier P. V.; Ma, Lan; Ren, Lei; Yousefi, BardiaAutomated medical data analysis demonstrated a significant role in modern medicine, and cancer diagnosis/prognosis to achieve highly reliable and generalizable systems. In this study, an automated breast cancer screening method in ultrasound imaging is proposed. A convolutional deep autoencoder model is presented for simultaneous segmentation and radiomic extraction. The model segments the breast lesions while concurrently extracting radiomic features. With our deep model, we perform breast lesion segmentation, which is linked to low-dimensional deep-radiomic extraction (four features). Similarly, we used high dimensional conventional imaging throughputs and applied spectral embedding techniques to reduce its size from 354 to 12 radiomics. A total of 780 ultrasound images—437 benign, 210, malignant, and 133 normal—were used to train and validate the models in this study. To diagnose malignant lesions, we have performed training, hyperparameter tuning, cross-validation, and testing with a random forest model. This resulted in a binary classification accuracy of 78.5% (65.1–84.1%) for the maximal (full multivariate) cross-validated model for a combination of radiomic groups.Item Development of an Endoscopic Auto-Fluorescent Sensing Device to Aid in the Detection of Breast Cancer and Inform Photodynamic Therapy(MDPI, 2022-11-11) Gaitan, Brandon; Inglut, Collin; Kanniyappan, Udayakumar; Xu, He N.; Conant, Emily F.; Frankle, Lucas; Li, Lin Z.; Chen, Yu; Huang, Huang-ChiaoBreast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are autofluorescent biomarkers that lend insight into cell and tissue metabolism. As such, we developed an endoscopic device to measure these metabolites in tissue to differentiate between malignant tumors and normal tissue. We performed initial validations in liquid phantoms as well as compared to a previously validated redox imaging system. We also imaged ex vivo tissue samples after modulation with carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and a combination of rotenone and antimycin A. We then imaged the rim and the core of MDA-MB-231 breast cancer tumors, with our results showing that the core of a cancerous lesion has a significantly higher optical redox ratio ([FAD]/([FAD] + [NADH])) than the rim, which agrees with previously published results. The mouse muscle tissues exhibited a significantly lower FAD, higher NADH, and lower redox ratio compared to the tumor core or rim. We also used the endoscope to measure NADH and FAD after photodynamic therapy treatment, a light-activated treatment methodology. Our results found that the NADH signal increases in the malignancy rim and core, while the core of cancers demonstrated a significant increase in the FAD signal.Item Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response(Impact Journals, 2016-02-08) Chakrabarti, Kristi R.; Andorko, James I.; Whipple, Rebecca A.; Zhang, Peipei; Sooklal, Elisabeth L.; Martin, Stuart S.; Jewell, Christopher M.Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high-resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis.Item Magnetic Drug Targeting: Developing the Basics(2013) Nacev, Aleksandar Nelson; Shapiro, Benjamin; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Focusing medicine to disease locations is a needed ability to treat a variety of pathologies. During chemotherapy, for example, typically less than 0.1% of the drugs are taken up by tumor cells, with the remaining 99.9% going into healthy tissue. Physicians often select the dosage by how much a patient can physically withstand rather than by how much is needed to kill all the tumor cells. The ability to actively position medicine, to physically direct and focus it to specific locations in the body, would allow better treatment of not only cancer but many other diseases. Magnetic drug targeting (MDT) harnesses therapeutics attached to magnetizable particles, directing them to disease locations using magnetic fields. Particles injected into the vasculature will circulate throughout the body as the applied magnetic field is used to attempt confinement at target locations. The goal is to use the reservoir of particles in the general circulation and target a specific location by pulling the nanoparticles using magnetic forces. This dissertation adds three main advancements to development of magnetic drug targeting. Chapter 2 develops a comprehensive ferrofluid transport model within any blood vessel and surrounding tissue under an applied magnetic field. Chapter 3 creates a ferrofluid mobility model to predict ferrofluid and drug concentrations within physiologically relevant tissue architectures established from human autopsy samples. Chapter 4 optimizes the applied magnetic fields within the particle mobility models to predict the best treatment scenarios for two classes of chemotherapies for treating future patients with hepatic metastatic breast cancer microtumors.Item Development of Carbon Nanotube Field-Effect Transistor Arrays for Detection of HER2 Overexpression in Breast Cancer(2011) Aschenbach, Konrad Hsu; Gomez, Romel D; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We developed a carbon nanotube biosensor platform that was deployed at the National Cancer Institute and successfully detected the HER2 oncogene in real cancer cells at clinically relevant levels. HER2 is a receptor protein that resides on the surface of certain cancer cells and is associated with higher aggressiveness in breast cancers. Overabundance of HER2 at the chromosomal, cell surface, and intermediate gene expression levels can all indicate a dangerous HER2 status. At the present, testing for HER2 status requires labor-intensive laboratory procedures using expensive reagents. Cost remains the major barrier to widespread screening. We propose an integrated electronic testing platform based on direct label-free gene detection. The system would integrate the various labor-intensive processes that are usually performed by skilled laboratory technicians. The heart of the system is an array of carbon nanotube field-effect transistors that can detect unlabelled nucleic acids via their intrinsic electric charges. We developed a scalable fabrication technique for carbon nanotube biosensor arrays, hardware and software for data acquisition and analysis, theoretical models for detection mechanism, and protocols for immobilization of peptide nucleic acid probes and hybridization of nucleic acids extracted from cells. We demonstrated detection of HER2 from real cell lines which express cancer genes, thereby lowering the technological barrier towards commercialization of a low-cost gene expression biosensor. The system is suitable for lab-on-a-chip integration, which could bring rapid, low-cost cancer diagnoses into the clinical setting.Item A dual modality, DCE-MRI and x-ray, physical phantom for quantitative evaluation of breast imaging protocols(2010) Freed, Melanie; Badano, Aldo; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The current clinical standard for breast cancer screening is mammography. However, this technique has a low sensitivity which results in missed cancers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising technique for breast cancer diagnosis and has been reported as being superior to mammography for screening of high-risk women and evaluation of extent of disease. At the same time, low and variable specificity has been documented in the literature as well as a rising number of mastectomies possibly due to the increasing use of DCE-MRI. In this study, we developed and characterized a dual-modality, x-ray and DCE-MRI, anthropomorphic breast phantom for the quantitative assessment of breast imaging protocols. X-ray properties of the phantom were quantitatively compared with patient data, including attenuation coefficients, which matched human values to within the measurement error, and tissue structure using spatial covariance matrices of image data, which were found to be similar in size to patient data. Simulations of the phantom scatter-to-primary ratio (SPR) were produced and experimentally validated then compared with published SPR predictions for homogeneous phantoms. SPR values were as high as 85% in some areas and were heavily influenced by the heterogeneous tissue structure. MRI properties of the phantom, T1 and T2 relaxation values and tissue structure, were also quantitatively compared with patient data and found to match within two error bars. Finally, a dynamic lesion that mimics lesion border shape and washout curve shape was included in the phantom. High spatial and temporal resolution x-ray measurements of the washout curve shape were performed to determine the true contrast agent concentration as a function of time. DCE-MRI phantom measurements using a clinical imaging protocol were compared against the x-ray truth measurements. MRI signal intensity curves were shown to be less specific to lesion type than the x-ray derived contrast agent concentration curves. This phantom allows, for the first time, for quantitative evaluation of and direct comparisons between x-ray and MRI breast imaging modalities in the context of lesion detection and characterization.