Biomedical Engineering and Bioengineering Commons^™

Improving The Early Detection Of Cardiovascular Toxicity Secondary To Radiotherapy For Lung Cancer Via Patient-Specific Quantitative Magnetic Resonance Imaging, Alireza Omidi

Theses and Dissertations

Purpose: To assess the cardiopulmonary-induced dose variation on the left ventricle (LV) and evaluate the spatiotemporal evolution of cardiac/aortic function following radiotherapy (RT).

Methods: 8 lung cancer patients who were scheduled to receive RT were recruited for this study. Each patient underwent one 4D-CT at baseline. MRI scans including cine GRE, T1/T2, LGE, and 4D-flow were acquired at baseline, 3-months and 6-months post-RT to evaluate the cardiac/aortic function. Finally, image registration was used to assess the cardiopulmonary-induced dose variation on the LV.

Results: Mean RT-dose was minimum during inspiration and systole (at expiration). No significant differences were found in the …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Effect Of Viscoelasticity On Cellular Morphology And Activity, Thomas J. Petet Jr

Theses and Dissertations

It has been well established that there is a link between substrate stiffness and cellular activities such as proliferation, migration, and differentiation. Less characterized is the link between the time-dependent viscosity of a substrate with those cellular activities. To explore this, PDMS substrates were created with predictably tunable stiffness and viscosity parameters. A simulated model was also developed in parallel to explore the potential effects of viscosity in a computationally predictive way. It was found that the inclusion of viscosity caused a major paradigm shift to a non-zero substrate equilibrium that was sensitive to increases in the substrate stiffness. Finally, …

Improving Patient-Specific Assessments Of Regional Aortic Mechanics Via Quantitative Magnetic Resonance Imaging With Early Applications In Patients At Elevated Risk For Thoracic Aortopathy, Patrick A. Jones

Theses and Dissertations

Unstable aortic aneurysms and dissections are serious cardiovascular conditions associated with high mortality. The current gold standards for assessment of stability, however, rely on simple geometric measurements, like cross-sectional area or increased diameter between follow-up scans, and fail to incorporate information about underlying aortic mechanics. Displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) has been used previously to determine heterogeneous circumferential strain patterns in the aortas of healthy volunteers. Here, I introduce technical improvements to DENSE aortic analysis and early pilot application in patients at higher risk for the development of aortopathies. Modifications to the DENSE aortic postprocessing …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Quantification And Modeling Of Bladder Biomechanics Mechanisms Linking Spontaneous Rhythmic Contractions And Dynamic Elasticity To Detrusor Overactivity, Zachary E. Cullingsworth

Theses and Dissertations

Overactive bladder (OAB) is a chronic condition affecting approximately 20% of adults in the United States. Detrusor overactivity (DO) is the presence of non-voiding contractions in the detrusor (bladder) muscle during filling and is present in some individuals with OAB. DO is currently identified visually during a urodynamics (UD) study involving pressure catheters and filling and voiding of the bladder to evaluate function. UD provides limited subtyping of DO, and an incomplete understanding of mechanisms contributing to OAB.

Aim 1 of this study was to develop objective tools to quantify, subgroup and better understand …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

A Computational Assessment Of Lisfranc Injuries And Their Surgical Repairs, Michael Perez

Theses and Dissertations

While Lisfranc injuries in the mid foot are less common than other ankle and mid foot injuries, they pose challenges in both properly identifying them and treating them. When Lisfranc injuries are ligamentous and do not include obvious fractures, they are very challenging for clinicians to identify unless weight bearing radiographs are used. The result is that 20%-40% of Lisfranc injuries are missed in the initial evaluation. Even when injuries are correctly identified the outcomes of surgical procedures remain poor. Existing literature has compared the different surgical procedures but has not had a standard approach or procedures across studies. This …

Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott

Theses and Dissertations

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …

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 …

Improved Capability Of A Computational Foot/Ankle Model Using Artificial Neural Networks, Ruchi D. Chande

Theses and Dissertations

Computational joint models provide insight into the biomechanical function of human joints. Through both deformable and rigid body modeling, the structure-function relationship governing joint behavior is better understood, and subsequently, knowledge regarding normal, diseased, and/or injured function is garnered. Given the utility of these computational models, it is imperative to supply them with appropriate inputs such that model function is representative of true joint function. In these models, Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scans and literature inform the bony anatomy and mechanical properties of muscle and ligamentous tissues, respectively. In the case of the latter, literature reports …

Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr

Theses and Dissertations

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …

Polysaccharide-Based Shear Thinning Hydrogels For Three-Dimensional Cell Culture, Vasudha Surampudi

Theses and Dissertations

The recreation of the complicated tissue microenvironment is essential to reduce the gap between in vitro and in vivo research. Polysaccharide-based hydrogels form excellent scaffolds to allow for three-dimensional cell culture owing to the favorable properties such as capability to absorb large amount of water when immersed in biological fluids, ability to form “smart hydrogels” by being shear-thinning and thixotropic, and eliciting minimum immunological response from the host. In this study, the biodegradable shear-thinning polysaccharide, gellan-gum based hydrogel was investigated for the conditions and concentrations in which it can be applied for the adhesion, propagation and assembly of different mammalian …

Generation And Delivery Of Charged Aerosols To Infant Airways, Landon T. Holbrook

Theses and Dissertations

The administration of pharmaceutical aerosols to infants on mechanical ventilation needs to be improved by increasing the efficiency of delivery devices and creating better ways of evaluating potential therapies. Aerosolized medicines such as surfactants have been administered to ventilated infants with mixed results, but studies have shown improvement in respiratory function with a much lower dose than with liquid instillation through an endotracheal tube (ETT). An aerosolized medicine must be transported through the ventilation tubing and deposit in the lungs to have the desired therapeutic response.

This work has taken a systematic approach to (i) develop new devices for the …

Computational Modeling To Assess Surgical Procedures For The Treatment Of Adult Acquired Flatfoot Deformity, Brian A. Smith

Theses and Dissertations

Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures …

The Effects Of Fatigue On Lower Extremity Kinetics And Kinematics In Subjects With Known Ankle Instability, Lindsay E. Clayton

Theses and Dissertations

The goal of this study was to evaluate biomechanical differences between healthy subjects and those with ankle instability during the gradual onset of lower extremity fatigue from a landing activity. An understanding of these differences is needed in order to prevent future injury to or further debilitation in individuals with ankle instability. A functional fatiguing activity was designed to focus fatigue on the quadriceps muscles, as those are the muscles most frequently fatigued during sport. Measures were taken throughout the progression of fatigue with a force plate and a motion tracking system and included vertical ground reaction force and lower …

Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza

Theses and Dissertations

Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length …

Design And Validation Of A Computational Model For Study Of Scapholunate Joint Kinematics, Edward J. Tremols

Theses and Dissertations

As computational power has increased, computational modeling has become a very promising tool to model the biomechanics of complex joint systems. Musculoskeletal computational models have become more complex when compared to original iterations which utilized a number of simplifications. This thesis utilized a three-dimensional computational model of the wrist joint structure to investigate scapholunate kinematics. The model accurately represented the bony anatomy of the wrist and hand and represented soft tissue structures such as ligaments, tendons, and other surrounding tissues. Creation of the model was done using commercially available computer-aided design and medical image processing software, and utilized the rigid …