Biomedical Engineering and Bioengineering Commons^™

Identification Of Prognostic Cancer Biomarkers Through The Application Of Rna-Seq Technologies And Bioinformatics, Nathan Wong

McKelvey School of Engineering Graduate Student Theses & Dissertations

MicroRNAs (miRNAs) are short single-stranded RNAs that function as the guide sequence of the post-transcriptional regulatory process known as the RNA-induced silencing complex (RISC), which targets mRNA sequences for degradation through complementary binding to the guide miRNA. Changes in miRNA expression have been reported as correlated with numerous biological processes, including embryonic development, cellular differentiation, and disease manifestation. In the latter case, dysregulation has been observed in response to infection by human papillomavirus (HPV), which has also been established as both oncogenic in cervical cancers and oropharyngeal cancers and favorable for overall patient survival after tumor formation. The identification of …

Functional Bio-Nano Hybrids Through A Precise Control Of Interfacial Interactions At The Nanoscale, Sirimuvva Tadepalli

McKelvey School of Engineering Graduate Student Theses & Dissertations

During the course of evolution, proteins have evolved to perform exquisite functions including structural support, signal transduction, actuation, sensing, catalysis, trafficking, gating, light-harvesting, charge transfer, molecular recognition, self-assembly, self-organization, or combinations of two or more of these functions. A precise control and manipulation of the structure and function of proteins is conceivable with the advent of nanotechnology, which has facilitated the integration of nanomaterials with functional biomolecules to realize bio-nano hybrids with synergistically enhanced functionalities.

At the genesis of bionanotechnology, a paucity in the fundamental understanding of the bio-nano interfaces is a grave impediment to the progress of the field. …

Development Of In Vitro Drug Screening Platforms Using Human Induced Pluripotent Stem Cell-Derived Cardiovascular Cells, Yosuke Kurokawa

McKelvey School of Engineering Graduate Student Theses & Dissertations

Drug-induced cardiotoxicity is a critical challenge in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes (CMs), researchers have explored ways to utilize these cells for in vitro preclinical drug screening applications. One area of interest is microphysiological systems (i.e. organ-on-a-chip), which aims to create more complex in vitro models of human organ systems, thus improving drug response predictions. In this dissertation, we investigated novel analysis methods and model platforms for detecting drug-induced cardiotoxicity using human induced pluripotent stem cell (iPSC)-derived cardiovascular cells.

First, we utilized human iPSC-derived CMs (iPS-CMs) to establish optical methods of …

System Characterizations And Optimized Reconstruction Methods For Novel X-Ray Imaging, Huifeng Guan

McKelvey School of Engineering Graduate Student Theses & Dissertations

In the past decade there have been many new emerging X-ray based imaging technologies developed for different diagnostic purposes or imaging tasks. However, there exist one or more specific problems that prevent them from being effectively or efficiently employed. In this dissertation, four different novel X-ray based imaging technologies are discussed, including propagation-based phase-contrast (PB-XPC) tomosynthesis, differential X-ray phase-contrast tomography (D-XPCT), projection-based dual-energy computed radiography (DECR), and tetrahedron beam computed tomography (TBCT). System characteristics are analyzed or optimized reconstruction methods are proposed for these imaging modalities. In the first part, we investigated the unique properties of propagation-based phase-contrast imaging technique …

System Optimization And Iterative Image Reconstruction In Photoacoustic Computed Tomography For Breast Imaging, Yang Lou

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic computed tomography(PACT), also known as optoacoustic tomography (OAT), is an emerging imaging technique that has developed rapidly in recent years. The combination of the high optical contrast and the high acoustic resolution of this hybrid imaging technique makes it a promising candidate for human breast imaging, where conventional imaging techniques including X-ray mammography, B-mode ultrasound, and MRI suffer from low contrast, low specificity for certain breast types, and additional risks related to ionizing radiation. Though significant works have been done to push the frontier of PACT breast imaging, it is still challenging to successfully build a PACT breast imaging …

Image Reconstruction Of The Speed Of Sound And Initial Pressure Distributions In Ultrasound Computed Tomography And Photoacoustic Computed Tomography, Thomas Paul Matthews

McKelvey School of Engineering Graduate Student Theses & Dissertations

Ultrasound computed tomography (USCT) and photoacoustic computed tomography (PACT) are two emerging imaging modalities that have a wide range of potential applications from pre-clinical small animal imaging to cancer screening in human subjects. USCT is typically employed to measure acoustic contrasts, including the speed of sound (SOS) distribution, while PACT typically measures optical contrasts or some related quantity such as the initial pressure distribution. Their complementary contrasts and similar implementations make USCT and PACT a natural fit for a hybrid imaging system. Still, much work remains to realize this promise. First, USCT image reconstruction methods based on the acoustic wave …

Reconstruction Algorithms For Novel Joint Imaging Techniques In Pet, Homayoon Ranjbar

McKelvey School of Engineering Graduate Student Theses & Dissertations

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types.

The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as ¹¹C, ¹³N, and ¹⁸F, can be used to label molecules, and tracers, such …

Binding Affinity And Specificity Of Sh2 Domain Interactions In Receptor Tyrosine Kinase Signaling Networks, Tom Ronan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Receptor tyrosine kinase (RTK) signaling mechanisms play a central role in intracellular signaling and control development of multicellular organisms, cell growth, cell migration, and programmed cell death. Dysregulation of these signaling mechanisms results in defects of development and diseases such as cancer. Control of this network relies on the specificity and selectivity of Src Homology 2 (SH2) domain interactions with phosphorylated target peptides. In this work, we review and identify the limitations of current quantitative understanding of SH2 domain interactions, and identify severe limitations in accuracy and availability of SH2 domain interaction data. We propose a framework to address some …

Next Generation Sequencing Technologies For Real-Time Genotyping And Targeted Sequencing For Precision Medicine, Priyanka Rawat

Biomedical Engineering ETDs

Astounding success of Human genome project and accelerating success of sequencing technologies have enabled $ 1000 genome goals possible. But, this is still far-fetched from the reach of many resource refrained populations with high genetic variations causing lethal genetic diseases. Based on present technology principles, I have developed prototypes for affordable, scalable and customizable point-of-care genotyping and targeted sequencing. Ion-sensitive field effect transistors with novel read-out and signal amplification techniques are used for laying foundation of possible ISFET based allele-arrays. Sequencing-by-synthesis based full-fledge sequencer is made with novel immobilization, flow-cell and data acquisition methods for massive sequenciing.

Characterization Of Structural Dynamics Of The Human Head Using Magnetic Resonance Elastography, Andrew Arun Badachhape

McKelvey School of Engineering Graduate Student Theses & Dissertations

In traumatic brain injury (TBI), the skull-brain interface, composed of three meningeal layers: the dura mater, arachnoid mater, and pia mater, along with cerebrospinal fluid (CSF) between the layers, plays a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is a noninvasive imaging modality capable of providing in vivo estimates of tissue motion and material properties. The objective of this work is to augment human and phantom MRE studies to better characterize the mechanical contributions of the skull-brain interface to improve the parameterization and validation of computational models of TBI. Three specific aims …

Characterizing Anisotropy In Fibrous Soft Materials By Mr Elastography Of Slow And Fast Shear Waves, John Larson Schmidt

McKelvey School of Engineering Graduate Student Theses & Dissertations

The general objective of this work was to develop experimental methods based on magnetic resonance elastography (MRE) to characterize fibrous soft materials. Mathematical models of tissue biomechanics capable of predicting injury, such as traumatic brain injury (TBI), are of great interest and potential. However, the accuracy of predictions from such models depends on accuracy of the underlying material parameters. This dissertation describes work toward three aims. First, experimental methods were designed to characterize fibrous materials based on a transversely isotropic material model. Second, these methods are applied to characterize the anisotropic properties of white matter brain tissue ex vivo. Third, …

Comparison Of The Bi-Directional Performance Of Micro-Channel Sieve And Thin-Film Time Peripheral Nerve Interfaces, Robert Coker

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sophisticated motorized prosthetic limbs contain multiple degrees of freedom of motion as well as embedded pressure and angle transducers to provide sensory feedback in amputees. Although several central neural recording and stimulation modalities exist for both controlling these motions and providing sensory feedback from a prosthetic limb, directly interfacing the peripheral nerves which originally innervated the limb has many advantages. A difficulty with this bi-directional approach is that electrically stimulating axons to provide haptic feedback creates stimulation artifacts at neighboring recording sites within the nerve that are several orders of magnitude larger than the electroneurogram used for control. In this …

Bio-Inspired Multi-Spectral And Polarization Imaging Sensors For Image-Guided Surgery, Nimrod Missael Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Image-guided surgery (IGS) can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky, costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities to distinguish cancerous from healthy tissue. In my thesis, I have addressed these challenges in IGC by mimicking the visual systems of several animals to construct low power, compact and highly sensitive multi-spectral and color-polarization sensors. I …

Association Between Left Ventricular Mechanics And Diffuse Myocardial Fibrosis In Patients With Repaired Tetralogy Of Fallot: A Cross-Sectional Study, Christopher M. Haggerty, Jonathan D. Suever, Arichanah Pulenthiran, Abba Mejia-Spiegeler, Gregory J. Wehner, Linyuan Jing, Richard J. Charnigo, Brandon K. Fornwalt, Mark A. Fogel

Biomedical Engineering Faculty Publications

Background: Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse biventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this dysfunction, such as diffuse myocardial fibrosis, may provide insights into poor long-term outcomes. We hypothesized that left ventricular (LV) diffuse fibrosis is related to impaired LV mechanics.

Methods: Patients with TOF were evaluated with cardiac magnetic resonance in which modified Look-Locker (MOLLI) T1-mapping and spiral cine Displacement encoding (DENSE) sequences were acquired at three LV short-axis positions. Linear mixed modeling was used to define the association between regional LV mechanics from DENSE based on regional T1-derived diffuse …

Nanostructured Apatite-Mullite Glass-Ceramics For Enhanced Primary Human Osteoblast Cell Response, Gordon Cooke, Conor Dunne, Sarah Keane, Daithi De Faoite, Seamas Donnelly, Kenneth Stanton

Articles

This work investigates the difference in viability of primary human foetal osteoblast cells on a glass-ceramic surface with nanoscale topography relative to viability on a smooth glass-ceramic surface containing a bioactive phase. Apatite-mullite glass-ceramics containing bioactive fluorapatite (Ca₁₀(PO₄)₆F₂) and bioinert mullite (Si₂Al₆O₁₃) were synthesised and subsequent heat-treatment was optimised to form nano-sized fluorapatite crystals. Etching was used to selectively remove the bioactive phase, producing a surface with disordered nanoscale topography. Cells were seeded onto a smooth polished glass-ceramic substrate with the bioactive phase intact, an etched …

Reducing Biomass Recalcitrance By Heterologous Expression Of A Bacterial Peroxidase In Tobacco (Nicotiana Benthamiana), Ayalew Ligaba-Osena, Bertrand Hankoua, Kay Dimarco, Robert Pace, Mark Crocker, Jesse Mcatee, Nivedita Nagachar, Ming Tien, Tom L. Richard

Center for Applied Energy Research Faculty and Staff Publications

Commercial scale production of biofuels from lignocellulosic feed stocks has been hampered by the resistance of plant cell walls to enzymatic conversion, primarily owing to lignin. This study investigated whether DypB, the lignin-degrading peroxidase from Rodococcus jostii, depolymerizes lignin and reduces recalcitrance in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the cytosol or the ER using ER-targeting and retention signal peptides. For each construct, five independent transgenic lines were characterized phenotypically and genotypically. Our findings reveal that expression of DypB in the cytosol and ER does not affect plant development. ER-targeting increased protein accumulation, and …

Development Of Image Analysis Toolboxes For Biological Imaging, Samia Sanjari

Student Theses and Dissertations

The purpose of tissue engineering is to regenerate the damaged tissues by using three dimensional porous scaffolds which act as substrates for tissue regeneration. Several studies have showed that structural properties of scaffold (fiber diameter, pore size of scaffold, and fiber orientation) play a significant role in tissue regeneration. Therefore, in order to design a suitable scaffold for tissue engineering application, it is important to understand the structural properties of fibrous scaffold. To achieve this aim in this study, standalone image analysis toolboxes are generated by using the MATLAB software for finding the mean pore size of scaffolds, length, diameter …

Telesurgery: Surgery In The Digital Age, Dylan J. Cahill

Dartmouth Undergraduate Journal of Science

The dawn of the digital age has transformed the way we now receive and provide healthcare. Today, providers have instant access to all of their patients’ information, just as patients can connect with their providers on their smartphones in minutes from nearly anywhere in the world.

Effects Of Uniaxial Cyclic Strain On Endothelial Progenitor Cells, Maria Alejandra Zeballos Castro

Biomedical Engineering Undergraduate Honors Theses

Despite the high prevalence of calcific aortic valve disease (CAVD), the underlying mechanisms of pathogenesis have not been found yet. Therefore, it is extremely important to study CAVD and understand how it develops. For this matter, we decided to study the potential of endothelial progenitor cells (EPCs) for use in tissue-engineered models of heart valves. EPCs were chosen as the cell source of interest for this study due to their high neovascularization potential and use in regenerative medicine and cardiovascular tissue engineering.

In this project, we aimed to engineer the microenvironment of cells that are involved in the formation of …

Revealing Hemodynamic Response And Dynamic Changes In Functional Cortical Networks Using Functional Near-Infrared Spectroscopy (Fnirs), Jianwei Cao

Bioengineering Dissertations - Archive

Therapeutic interventions, such as physical therapy and non-invasive brain electrical stimulation can enhance the physical performance of persons with brain disorders. One often-used form of physical therapy named constraint-induced movement therapy (CIMT) improves motor control skills of children with cerebral palsy (CP) through forced intensive use of the affected extremity. A complementary method to physical rehabilitation methods for overcoming a deficit is to facilitate use of the affected brain areas by non-invasive brain electrical stimulation. One currently popular form of brain stimulation is transcranial direct current stimulation (tDCS), which has been shown to enhance both motor and language performance in …