Biomedical Engineering and Bioengineering Commons^™

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 …

Characterization Of The Response Of Trpv4 To Chemical Stimulation, Jacob V. Schluns

Biomedical Engineering Undergraduate Honors Theses

Traumatic Brain Injury (TBI) is a source of acute and chronic health issues for many patients. One of the components of the brain’s response to injury is astrogliosis, in which astrocytes that normally function to repair the brain instead form scar tissue that halts repair processes. Transient Receptor Potential Vanilloid Type 4 (TRPV4) is a trans-membrane calcium channel involved in astrogliosis. Through Fura-2AM based calcium imaging, the base activity of this channel in mouse astrocyte cells was recorded. The cells were then subjected to TRPV4 agonist and antagonist stimulation and their subsequent activity levels were recorded. The data showed that …

Optimizing A Standard Fasting Time For 2-Nbdg Uptake Studies In Murine Breast Cancers, Andrew C. Briley

Biomedical Engineering Undergraduate Honors Theses

Recently, there has been a larger use of 2-NBDG, a fluorescent glucose analog, to study glucose uptake in different cell types. These cell types have ranged anywhere from bacteria to human cancer cells. However, there has yet to be a standard procedure and practice for using 2-NBDG. In this study, our goal is to create a standard fasting time for the cells before introducing 2-NBDG to them. This study uses 4T07 cells, a murine breast cancer cell line, to help optimize this fasting time. These cells were fasted at different time points in order to find the ideal fasting time. …

In Vivo Multi-Parametric Imaging Of Metastatic And Non-Metastatic Breast Cancer, Raisa B. Rasul

Biomedical Engineering Undergraduate Honors Theses

A current issue in cancer therapy is the characterization of metastatic tumors, which can increase ease of treatment and patient trials. We present an in vivo study of metastatic (4T1) and non-metastatic (4T1-TWIST KO) breast tumor sister cell lines to understand their metabolic behavior, determine differences in two modes of imaging (reflection & transmission), and observe effect of breathing higher oxygen percentage on vascular hemoglobin oxygen saturation. After injection of 10,000 cells into mice dorsal window chambers, the glucose intake and hemoglobin oxygen saturation was measured using a fluorescent glucose analog (2-NBDG) and hyperspectral trans-illumination imaging from 520-620 nm at …

Metabolic Response To Stress Differentiates Heterogeneous Cancer Cells With Varying Metastatic Potential, Kinan Alhallak

Biomedical Engineering Undergraduate Honors Theses

Intratumoral heterogeneity is ubiquitously present within primary tumors and contributes to intractable behaviors such as metastasis and mutability spatiotemporally. Mounting evidence has shown that heterogeneous cell populations can adversely affect cell metabolism and metastatic potential. The cell’s only fluorescent molecules within the electron transport chain, flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH), can allow the quantitation of cell metabolism. We demonstrate the use of the optical redox ratio (FAD/(NADH+FAD)) to determine the metabolic behaviors of a heterogeneous panel of cells with varying metastatic programs at normal conditions and following acute hypoxia. At normal conditions, we reveal an attenuation …

Optimization Of Fluorescent Imaging In The Operating Room Through Pulsed Acquisition And Gating To Ambient Background Cycling, Kristian J. Sexton, Yan Zhao, Scott C. Davis, Shudong Jiang, Brian Pogue

Dartmouth Scholarship

The design of fluorescence imaging instruments for surgical guidance is rapidly evolving, and a key issue is to efficiently capture signals with high ambient room lighting. Here, we introduce a novel time-gated approach to fluorescence imaging synchronizing acquisition to the 120 Hz light of the room, with pulsed LED excitation and gated ICCD detection. It is shown that under bright ambient room light this technique allows for the detection of physiologically relevant nanomolar fluorophore concentrations, and in particular reduces the light fluctuations present from the room lights, making low concentration measurements more reliable. This is particularly relevant for the light …

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 …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Directed Acyclic Graph Continuous Max-Flow Image Segmentation For Unconstrained Label Orderings, John Sh Baxter, Martin Rajchl, A. Jonathan Mcleod, Jing Yuan, Terry M. Peters

Robarts Imaging Publications

Label ordering, the specification of subset–superset relationships for segmentation labels, has been of increasing interest in image segmentation as they allow for complex regions to be represented as a collection of simple parts. Recent advances in continuous max-flow segmentation have widely expanded the possible label orderings from binary background/foreground problems to extendable frameworks in which the label ordering can be specified. This article presents Directed Acyclic Graph Max-Flow image segmentation which is flexible enough to incorporate any label ordering without constraints. This framework uses augmented Lagrangian multipliers and primal–dual optimization to develop a highly parallelized solver implemented using GPGPU. This …

Ex Vivo Bio-Orthogonal Mri Imaging – A Novel Method Proposed For Metastatic Cancer Detection, Tanner Ravsten, William G. Pitt, Neal K. Bangerter, Randy Hartley, Forrest Howell, Jessica Doud

Biomedical Engineering Western Regional Conference

Bio-orthogonal detection of metastatic cancer using MRI, Gd Iron-oxide contrast agents using T1 T2* scans

Mri Field Mapping Using Bssfp Elliptical Signal Model, Joseph Valentine, Meredith Taylor, Steven Whitaker, Michael Hoff, Neal Bangerter

Biomedical Engineering Western Regional Conference

MRI, Field Mapping, bSSFP, ssfp, Elliptical Signal model, ellipse, phase unwrapping

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

Biomedical Engineering Western Regional Conference

No abstract provided.

Resting State Functional Network Disruptions In A Kainic Acid Model Of Temporal Lobe Epilepsy., Ravnoor Singh Gill, Seyed M Mirsattari, L Stan Leung

Physiology and Pharmacology Publications

We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE) in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD) signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN). The …

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.

A Structural And Functional Analysis Of Human Brain Mri With Attention Deficit Hyperactivity Disorder, Arjun A. Watane

Honors Undergraduate Theses

Attention Deficit Hyperactivity Disorder (ADHD) affects 5-10% of children worldwide. Its effects are mainly behavioral, manifesting in symptoms such as inattention, hyperactivity, and impulsivity. If not monitored and treated, ADHD may adversely affect a child's health, education, and social life. Furthermore, the neurological disorder is currently diagnosed through interviews and opinions of teachers, parents, and physicians. Because this is a subjective method of identifying ADHD, it is easily prone to error and misdiagnosis. Therefore, there is a clear need to develop an objective diagnostic method for ADHD.

The focus of this study is to explore the use of machine language …

Validation, Optimization, And Image Processing Of Spiral Cine Dense Magnetic Resonance Imaging For The Quantification Of Left And Right Ventricular Mechanics, Gregory J. Wehner

Theses and Dissertations--Biomedical Engineering

Recent evidence suggests that cardiac mechanics (e.g. cardiac strains) are better measures of heart function compared to common clinical metrics like ejection fraction. However, commonly-used parameters of cardiac mechanics remain limited to just a few measurements averaged over the whole left ventricle. We hypothesized that recent advances in cardiac magnetic resonance imaging (MRI) could be extended to provide measures of cardiac mechanics throughout the left and right ventricles (LV and RV, respectively).

Displacement Encoding with Stimulated Echoes (DENSE) is a cardiac MRI technique that has been validated for measuring LV mechanics at a magnetic field strength of 1.5 T but …

Automatic Optimum Atlas Selection For Multi-Atlas Image Segmentation Using Joint Label Fusion, Kofi Agyeman

Dissertations and Theses

Multi-atlas image segmentation using label fusion is one of the most accurate state of the art image segmentation techniques available for biomedical imaging applications. Motivated to achieve higher image segmentation accuracy, reduce computational costs and a continuously increasing atlas data size, a robust framework for optimum selection of atlases for label fusion is vital. Although believed not to be critical for weighted label fusion techniques by some works (Sabuncu, M. R. et al., 2010, [1]), others have shown that appropriate atlas selection has several merits and can improve multi-atlas image segmentation accuracy (Aljabar et al., 2009, [2], Van de Velde …

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 …

The Viability Of Advantg Deterministic Method For Synthetic Radiography Generation, Andrew Albert Bingham

Masters Theses

"Time sensitive and high resolution image simulations are needed for synthetic radiography generation. The standard stochastic approach requires lengthy run times with poor statistics at higher resolutions. The investigation of the viability of a deterministic approach to synthetic radiography image generation was explored. The aim was to analyze a computational time decrease over the stochastic method. ADVANTG was compared to MCNP in multiple scenarios including a Benchtop CT prototype, to simulate high resolution radiography images. By using ADVANTG deterministic code to simulate radiography images the computational time was found to decrease over 10 times compared to the MCNP stochastic approach"--Abstract, …

Development And Validation Of A Novel Resonant Energy Transfer (Fret) Biosensor To Measure Tensile Forces At The Linc Complex In Live Cells, Paul Arsenovic

Theses and Dissertations

There is a large body of evidence supporting the theory that cell physiology largely depends on the mechanical properties of its surroundings or micro-environment. More recently studies have shown that changes to intra-cellular mechanical properties can also have a meaningful impact on cell function and in some cases lead to the progression of ailments or disease. For example, small changes to the protein sequence of a structural nuclear envelope protein called lamin-A is known to cause a variety of neurological and musculoskeletal diseases referred to as laminopathies. Currently, there is little incite into how these mutations lead to disease progression …

Computational Ultrasound Elastography: A Feasibility Study, Yu Wang

Dissertations, Master's Theses and Master's Reports

Ultrasound Elastography (UE) is an emerging set of imaging modalities used to assess the biomechanical properties of soft tissues. UE has been applied to numerous clinical applications. Particularly, results from clinical trials of UE in breast lesion differentiation and staging liver fibrosis indicated that there was a lack of confidence in UE measurements or image interpretation. Confidence on UE measurements interpretation is critically important for improving the clinical utility of UE. The primary objective of my thesis is to develop a computational simulation platform based on open-source software packages including Field II, VTK, FEBio and Tetgen. The proposed virtual simulation …

Development Of Breast Tissue Phantoms For Enhanced Terahertz Imaging Utilizing Microdiamond And Nano-Onion Particles, Alec Walter

Electrical Engineering Undergraduate Honors Theses

This thesis presents the work performed to develop tissue phantoms and a contrast agent that will be used in future research of terahertz time-domain imaging of breast tumor margins. Since an excised breast tumor can contain healthy fibrous and fatty tissues along with invasive ductal carcinoma (IDC), three phantom materials were developed. Solid phantom materials were made by using TX151 to solidify water in order to tune the refractive index and absorption coefficient of the fibrous tissue phantom and IDC phantom to the properties of freshly excised breast tissue. Various amounts of olive oil were added to the water prior …

Raman Spectroscopy Detects Distant Invasive Brain Cancer Cells Centimeters Beyond Mri Capability In Humans, Michael Jermyn, Joannie Desroches, Jeanne Mercier, Karl St-Arnaud

Dartmouth Scholarship

Surgical treatment of brain cancer is limited by the inability of current imaging capabilities such as magnetic resonance imaging (MRI) to detect the entirety of this locally invasive cancer. This results in residual cancer cells remaining following surgery, leading to recurrence and death. We demonstrate that intraoperative Raman spectroscopy can detect invasive cancer cells centimeters beyond pathological T1-contrast-enhanced and T2-weighted MRI signals. This intraoperative optical guide can be used to detect invasive cancer cells and minimize post-surgical cancer burden. The detection of distant invasive cancer cells beyond MRI signal has the potential to increase the effectiveness of surgery and directly …

Shape Complexes: The Intersection Of Label Orderings And Star Convexity Constraints In Continuous Max-Flow Medical Image Segmentation., John S H Baxter, Jiro Inoue, Maria Drangova, Terry M Peters

Robarts Imaging Publications

Optimization-based segmentation approaches deriving from discrete graph-cuts and continuous max-flow have become increasingly nuanced, allowing for topological and geometric constraints on the resulting segmentation while retaining global optimality. However, these two considerations, topological and geometric, have yet to be combined in a unified manner. The concept of "shape complexes," which combine geodesic star convexity with extendable continuous max-flow solvers, is presented. These shape complexes allow more complicated shapes to be created through the use of multiple labels and super-labels, with geodesic star convexity governed by a topological ordering. These problems can be optimized using extendable continuous max-flow solvers. Previous approaches …

A Fourier Description Of Covariance, And Separation Of Simultaneously Encoded Slices With In-Plane Acceleration In Fmri, Mary C. Kociuba

Dissertations (1934 -)

Functional magnetic resonance imaging (fMRI) studies aim to identify localized neural regions associated with a cognitive task performed by the subject. An indirect measure of the brain activity is the blood oxygenation level dependent (BOLD) signal fluctuations observed within the complex-valued spatial frequencies measured over time. The standard practice in fMRI is to discard the phase information after image reconstruction, even with evidence of biological task-related change in the phase time-series. In the first aim of this dissertation, a complex-valued time-series covariance is derived as a linear combination of second order temporal Fourier frequency coefficients. As opposed to magnitude-only analysis, …

Microdose Fluorescence Imaging Of Aby-029 On An Operating Microscope Adapted By Custom Illumination And Imaging Modules, Jonathan T. Elliott, Alisha V. Dsouza, Kayla Marra, Brian W. Pogue, David Roberts, Keith Paulsen

Dartmouth Scholarship

Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials.

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemoradiation Therapy Outcomes, Lixin Dong, Mahesh Kudrimoti, Daniel Irwin, Li Chen, Sameera Kumar, Yu Shang, Chong Huang, Ellis L. Johnson, Scott D. Stevens, Brent J. Shelton, Guoqiang Yu

Biomedical Engineering Faculty Publications

This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n = 29) and incomplete response (IR) (n = 18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 …

Low-Cost Compact Diffuse Speckle Contrast Flowmeter Using Small Laser Diode And Bare Charge-Coupled-Device, Chong Huang, Myeongsu Seong, Joshua Paul Morgan, Siavash Mazdeyasna, Jae Gwan Kim, Jeffrey Todd Hastings, Guoqiang Yu

Biomedical Engineering Faculty Publications

We report a low-cost compact diffuse speckle contrast flowmeter (DSCF) consisting of a small laser diode and a bare charge-coupled-device (CCD) chip, which can be used for contact measurements of blood flow variations in relatively deep tissues (up to ∼8  mm). Measurements of large flow variations by the contact DSCF probe are compared to a noncontact CCD-based diffuse speckle contrast spectroscopy and a standard contact diffuse correlation spectroscopy in tissue phantoms and a human forearm. Bland–Altman analysis shows no significant bias with good limits of agreement among these measurements: 96.5% ± 2.2% (94.4% to 100.0%) in phantom experiments and 92.8% …

3d Modeling Of Murine Abdominal Aortic Aneurysms: Quantification Of Segmentation And Volumetric Reconstruction, Paula A. Sarmiento, Amelia R. Adelsperger, Craig J. Goergen Ph.D.

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal Aortic Aneurysms (AAA) cause 5,900 deaths in the United States each year. Surgical intervention is clinically studied by non-invasive techniques such as computed tomography and magnetic resonance imaging. However, three-dimensional (3D) ultrasound imaging has become an inexpensive alternative and useful tool to characterize aneurysms, allowing for reconstruction of the vessel, quantification of hemodynamics through computational fluid dynamics (CFD) simulation, and possible prediction of aortic expansion and rupture. However, current analysis techniques for these images require the use of multiple software platforms for either modeling or simulation, prompting the need for alternatives to improve data processing. This study monitors the …