Biomedical Engineering and Bioengineering Commons^™

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 …

3d Microwave Tomography Using The Soft Prior Regularization Technique: Evaluation In Anatomically-Realistic Mri-Derived Numerical Breast Phantoms, Amir H. Golnabi, Paul M. Meaney, Shireen D. Geimer, Keith D. Paulsen

Department of Mathematics Faculty Scholarship and Creative Works

Objective: Fusion of magnetic resonance imaging (MRI) breast images with microwave tomography is accomplished through a soft prior technique, which incorporates spatial information (from MRI), i.e. accurate boundary location of different regions of interest, into the regularization process of the microwave image reconstruction algorithm. Methods: Numerical experiments were completed on a set of 3D breast geometries derived from MR breast data with different parenchymal densities, as well as a simulated tumor to evaluate performance over a range of breast shapes, sizes and property distributions. Results: When the soft prior regularization technique was applied, both permittivity and conductivity relative root mean …

Abso2luteu-Net: Tissue Oxygenation Calculation Using Photoacoustic Imaging And Convolutional Neural Networks, Kevin Hoffer-Hawlik, Geoffrey P. Luke

ENGS 88 Honors Thesis (AB Students)

Photoacoustic (PA) imaging uses incident light to generate ultrasound signals within tissues. Using PA imaging to accurately measure hemoglobin concentration and calculate oxygenation (sO₂) requires prior tissue knowledge and costly computational methods. However, this thesis shows that machine learning algorithms can accurately and quickly estimate sO₂. absO₂luteU-Net, a convolutional neural network, was trained on Monte Carlo simulated multispectral PA data and predicted sO₂ with higher accuracy compared to simple linear unmixing, suggesting machine learning can solve the fluence estimation problem. This project was funded by the Kaminsky Family Fund and the Neukom Institute.

Calibrated Short Tr Recovery Mri For Rapid Measurement Of Brain-Blood Partition Coefficient And Correction Of Quantitative Cerebral Blood Flow, Scott William Thalman

Theses and Dissertations--Biomedical Engineering

The high prevalence and mortality of cerebrovascular disease has led to the development of several methods to measure cerebral blood flow (CBF) in vivo. One of these, arterial spin labeling (ASL), is a quantitative magnetic resonance imaging (MRI) technique with the advantage that it is completely non-invasive. The quantification of CBF using ASL requires correction for a tissue specific parameter called the brain-blood partition coefficient (BBPC). Despite regional and inter-subject variability in BBPC, the current recommended implementation of ASL uses a constant assumed value of 0.9 mL/g for all regions of the brain, all subjects, and even all species.

The …

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 …

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 and Aerospace 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 …

Effect Of Hypoxia On Spontaneous Neural Activity In The Cortex Of Neonate Mouse Pups, Krithikka Ravi Ms

Dissertations and Theses

Hypoxia caused by inadequate oxygenation has profound effects on the normal functioning of the brain in mammals. Acute or chronic hypoxic insults occur in the brain depending on the duration of hypoxic exposure. Hypoxia is known to occur in the human womb and exerts adverse effects on the developing fetus. Most of the ongoing research on hypoxia is performed on rodent brain slice taken from various brain regions using intracellular recording. Extensive work has been carried out to understand the effects of chronic hypoxia on the developing nervous system, specifically during intrauterine development. However, effects of acute hypoxia occurring perinatally, …

Textured Contact Lens Based Iris Presentation Attack In Uncontrolled Environment, Daksha Yadav

Graduate Theses, Dissertations, and Problem Reports (ETD)

The widespread use of smartphones has spurred the research in mobile iris devices. Due to their convenience, these mobile devices are also utilized in unconstrained outdoor conditions. At the same time, iris recognition in the visible spectrum has developed into an active area of research. These scenarios have necessitated the development of reliable iris recognition algorithms for such an uncontrolled environment. Additionally, iris presentation attacks such as textured contact lens pose a major challenge to current iris recognition systems.

Motivated by these factors, in this thesis, a detailed analysis of the effect of textured contact lenses on iris recognition in …

Optical Vortex And Poincaré Analysis For Biophysical Dynamics, Anindya Majumdar

Dissertations, Master's Theses and Master's Reports

Coherent light - such as that from a laser - on interaction with biological tissues, undergoes scattering. This scattered light undergoes interference and the resultant field has randomly added phases and amplitudes. This random interference pattern is known as speckles, and has been the subject of multiple applications, including imaging techniques. These speckle fields inherently contain optical vortices, or phase singularities. These are locations where the intensity (or amplitude) of the interference pattern is zero, and the phase is undefined.

In the research presented in this dissertation, dynamic speckle patterns were obtained through computer simulations as well as laboratory setups …

Applications Of Machine Learning In Nuclear Imaging And Radiation Detection, Shaikat Mahmood Galib

Doctoral Dissertations

"The main focus of this work is to use machine learning and data mining techniques to address some challenging problems that arise from nuclear data. Specifically, two problem areas are discussed: nuclear imaging and radiation detection. The techniques to approach these problems are primarily based on a variant of Artificial Neural Network (ANN) called Convolutional Neural Network (CNN), which is one of the most popular forms of 'deep learning' technique.

The first problem is about interpreting and analyzing 3D medical radiation images automatically. A method is developed to identify and quantify deformable image registration (DIR) errors from lung CT scans …

Glioma Grading Using Structural Magnetic Resonance Imaging And Molecular Data, Syed M.S. Reza, Manar D. Samad, Zeina A. Shboul, Karra A. Jones, Khan M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

A glioma grading method using conventional structural magnetic resonance image (MRI) and molecular data from patients is proposed. The noninvasive grading of glioma tumors is obtained using multiple radiomic texture features including dynamic texture analysis, multifractal detrended fluctuation analysis, and multiresolution fractal Brownian motion in structural MRI. The proposed method is evaluated using two multicenter MRI datasets: (1) the brain tumor segmentation (BRATS-2017) challenge for high-grade versus low-grade (LG) and (2) the cancer imaging archive (TCIA) repository for glioblastoma (GBM) versus LG glioma grading. The grading performance using MRI is compared with that of digital pathology (DP) images in the …

End-To-End Learning Via A Convolutional Neural Network For Cancer Cell Line Classification, Darlington A. Akogo, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Purpose: Computer vision for automated analysis of cells and tissues usually include extracting features from images before analyzing such features via various machine learning and machine vision algorithms. The purpose of this work is to explore and demonstrate the ability of a Convolutional Neural Network (CNN) to classify cells pictured via brightfield microscopy without the need of any feature extraction, using a minimum of images, improving work-flows that involve cancer cell identification.

Design/methodology/approach: The methodology involved a quantitative measure of the performance of a Convolutional Neural Network in distinguishing between two cancer lines. In their approach, they trained, validated and …

Basis Vector Model Method For Proton Stopping Power Estimation Using Dual-Energy Computed Tomography, Shuangyue Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate estimation of the proton stopping power ratio (SPR) is important for treatment planning and dose prediction for proton beam therapy. The state-of-the-art clinical practice for estimating patient-specific SPR distributions is the stoichiometric calibration method using single-energy computed tomography (SECT) images, which in principle may introduce large intrinsic uncertainties into estimation results. One major factor that limits the performance of SECT-based methods is the Hounsfield unit (HU) degeneracy in the presence of tissue composition variations. Dual-energy computed tomography (DECT) has shown the potential of reducing uncertainties in proton SPR prediction via scanning the patient with two different source energy spectra. …

Manganese-Enhanced Magnetic Resonance Imaging: Overview And Central Nervous System Applications With A Focus On Neurodegeneration, Ryan A. Cloyd, Shon A. Koren, Jose F. Abisambra

Physiology Faculty Publications

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and …

Morphological Features Of Dysplastic Progression In Epithelium: Quantification Of Cytological, Microendoscopic, And Second Harmonic Generation Images, Sandra Patricia Gordon

Graduate Theses and Dissertations

Advances in imaging technology have led to a variety of available clinical and investigational systems. In this collection of studies, we tested the relevance of morphological image feature quantification on several imaging systems and epithelial tissues. Quantification carries the benefit of creating numerical baselines and thresholds of healthy and abnormal tissues, to potentially aid clinicians in determining a diagnosis, as well as providing researchers with standardized, unbiased results for future dissemination and comparison.

Morphological image features in proflavine stained oral cells were compared qualitatively to traditional Giemsa stained cells, and then we quantified the nuclear to cytoplasm ratio. We determined …

Cherenkov Excited Short-Wavelength Infrared Fluorescence Imaging In Vivo With External Beam Radiation, Xu Cao, Shudong Jiang, Mengyu Jeremy Jia, Jason R. Gunn, Tianshun Miao, Scott C. Davis, Petr Bruza, Brian W. Pogue

Dartmouth Scholarship

Cherenkov emission induced by external beam radiation therapy from a clinical linear accelerator (LINAC) can be used to excite phosphors deep in biological tissues. As with all luminescence imaging, there is a desire to minimize the spectral overlap between the excitation light and emission wavelengths, here between the Cherenkov and the phosphor. Cherenkov excited short-wavelength infrared (SWIR, 1000 to 1700 nm) fluorescence imaging has been demonstrated for the first time, using long Stokes-shift fluorophore PdSe quantum dots (QD) with nanosecond lifetime and an optimized SWIR detection. The 1  /  λ2 intensity spectrum characteristic of Cherenkov emission leads to low overlap …

Dual-Display Laparoscopic Laser Speckle Contrast Imaging For Real-Time Surgical Assistance, Jaepyeong Cha, Corey Zheng, Lung Wai Lau

Pediatrics Faculty Publications

Laser speckle contrast imaging (LSCI) utilizes the speckle pattern of a laser to determine the blood flow in tissues. The current approaches for its use in a clinical setting require a camera system with a laser source on a separate optical axis making it unsuitable for minimally invasive surgery (MIS). With blood flow visualization, bowel viability, for example, can be determined. Thus, LSCI can be a valuable tool in gastrointestinal surgery. In this work, we develop the first-of-its-kind dual-display laparoscopic vision system integrating LSCI with a commercially available 10mm rigid laparoscope where the laser has the same optical axis as …

Review Of Methods For Intraoperative Margin Detection For Breast Conserving Surgery, Benjamin W. Maloney, David M. Mcclatchy, Brian W. Pogue, Keith D. Paulsen, Wendy A. Wells, Richard J. Barth

Dartmouth Scholarship

Breast conserving surgery (BCS) is an effective treatment for early-stage cancers as long as the margins of the resected tissue are free of disease according to consensus guidelines for patient management. However, 15% to 35% of patients undergo a second surgery since malignant cells are found close to or at the margins of the original resection specimen. This review highlights imaging approaches being investigated to reduce the rate of positive margins, and they are reviewed with the assumption that a new system would need high sensitivity near 95% and specificity near 85%. The problem appears to be twofold. The first …

Hyperspectral Imaging For Characterizing Single Plasmonic Nanostructure And Single-Cell Analysis, Nishir Sanatkumar Mehta

LSU Master's Theses

Orientation of plasmonic nanostructures is an important feature in many nanoscale applications such as photovoltaics, catalyst, biosensors DNA interactions, protein detections, hotspot of surface-enhanced Raman spectroscopy (SERS), and fluorescence resonant energy transfer (FRET) experiments. Silver nanocubes with significant spectral signatures between 400-700 nm are observed in this experimental research. Whereas study of single cells will enable the analysis of cell-to-cell variations within a heterogeneous population. These variations are important for further analysis and understanding of disease propagation, drug development, stem cell differentiation, embryos development, and how cells respond to each other and their environment. Adipose-derived mesenchymal stem cells possess the …

Optical And X-Ray Technology Synergies Enabling Diagnostic And Therapeutic Applications In Medicine, Brian W. Pogue, Brian C. Wilson

Dartmouth Scholarship

X-ray and optical technologies are the two central pillars for human imaging and therapy. The strengths of x-rays are deep tissue penetration, effective cytotoxicity, and the ability to image with robust projection and computed-tomography methods. The major limitations of x-ray use are the lack of molecular specificity and the carcinogenic risk. In comparison, optical interactions with tissue are strongly scatter dominated, leading to limited tissue penetration, making imaging and therapy largely restricted to superficial or endoscopically directed tissues. However, optical photon energies are comparable with molecular energy levels, thereby providing the strength of intrinsic molecular specificity. Additionally, optical technologies are …

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 …

Perspective Review Of What Is Needed For Molecular-Specific Fluorescence-Guided Surgery, Brian W. Pogue, Eben L. Rosenthal, Samuel Achilefu, Gooitzen M. Van Dam

Dartmouth Scholarship

Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. As a whole, there are incredibly positive indicators of growth, including the first United States Food and Drug Administration clearance of an enzyme-biosynthetic-activated probe for surgery guidance, and a growing number of companies producing agents and imaging systems. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. A key issue to solve is the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery …

Light Scattering Measured With Spatial Frequency Domain Imaging Can Predict Stromal Versus Epithelial Proportions In Surgically Resected Breast Tissue, David M. Mcclatchy, Elizabeth J. Rizzo, Wendy A. Wells, Candice C. Black, Keith D. Paulsen, Stephen C. Kanick, Brian W. Pogue

Dartmouth Scholarship

This study aims to determine if light scatter parameters measured with spatial frequency domain imaging (SFDI) can accurately predict stromal, epithelial, and adipose fractions in freshly resected, unstained human breast specimens. An explicit model was developed to predict stromal, epithelial, and adipose fractions as a function of light scattering parameters, which was validated against a quantitative analysis of digitized histology slides for N  =  31 specimens using leave-one-out cross-fold validation. Specimen mean stromal, epithelial, and adipose volume fractions predicted from light scattering parameters strongly correlated with those calculated from digitized histology slides (r  =  0.90, 0.77, and 0.91, respectively, p-value× …

Quantifying Cancer Cell Receptors With Paired-Agent Fluorescent Imaging: A Novel Method To Account For Tissue Optical Property Effects., Negar Sadeghipour, Scott C. Davis, Kenneth M. Tichauer

Dartmouth Scholarship

Dynamic fluorescence imaging approaches can be used to estimate the concentration of cell surface receptorsin vivo. Kinetic models are used to generate the final estimation by taking the targeted imaging agent concentration as a function of time. However, tissue absorption and scattering properties cause the final readout signal to be on a different scale than the real fluorescent agent concentration. In paired-agent imaging approaches, simultaneous injection of a suitable control imaging agent with a targeted one can account for non-specific uptake and retention of the targeted agent. Additionally, the signal from the control agent can be a normalizing …

In Vivo Brainstem Imaging In Alzheimer’S Disease: Potential For Biomarker Development, David J. Braun, Linda J. Van Eldik

Neuroscience Faculty Publications

The dearth of effective treatments for Alzheimer’s disease (AD) is one of the largest public health issues worldwide, costing hundreds of billions of dollars per year. From a therapeutic standpoint, research efforts to date have met with strikingly little clinical success. One major issue is that trials begin after substantial pathological change has occurred, and it is increasingly clear that the most effective treatment regimens will need to be administered earlier in the disease process. In order to identify individuals within the long preclinical phase of AD who are likely to progress to dementia, improvements are required in biomarker development. …

Grant Funding Needs Parallel The Start-Up Venture: An Analogy For Translational Research Success, Brian W. Pogue

Dartmouth Scholarship

This editorial offers some ways to think about how best to position a research group for funding, by examining the parallels between what is needed for translational grants versus industry start-ups.

In Vivo Vascular Imaging With Photoacoustic Microscopy, Hsun-Chia Hsu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) has received extensive attention in the last decade for its capability to provide label-free structural and functional imaging in biological tissue with highly scalable spatial resolution and penetration depth. Compared to modern optical modalities, PAT offers speckle-free images and is more sensitive to optical absorption contrast (with 100% relative sensitivity). By implementing different regimes of optical wavelength, PAT can be used to image diverse light-absorbing biomolecules. For example, hemoglobin is of particular interest in the visible wavelength regime owing to its dominant absorption, and lipids and water are more commonly studied in the near-infrared regime.

In …

Multi-Beam Scan Analysis With A Clinical Linac For High Resolution Cherenkov-Excited Molecular Luminescence Imaging In Tissue., Mengyu Jeremy Jia, Peter Bruza, Lesley A. Jarvis, David J. Gladstone, Brian W. Pogue

Dartmouth Scholarship

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images …

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 …