Biomedical Engineering and Bioengineering Commons^™

Development Of Novel Radiotracers For Pet Imaging Of Hdac-Mediated Epigenetic Regulation, Robin Edwards Bonomi

Wayne State University Dissertations

Over the past two decades, epigenetic regulation has become a rapidly growing, highly innovative and influential field of biology and medicine. Protein acetylation and deacetylation, two key epigenetic regulatory mechanisms, are mediated by histone acetylase transferases (HATs) and histone deacetylases (HDACs), respectively. To date, the vast majority of studies on epigenetic regulation have been conducted in cell cultures and tissue samples using conventional methodologies of molecular and cellular biology, which contain inherent limitations for monitoring therapy and disease. Therefore, there is a growing need for novel, advanced methodologies that allow for non-invasive detection and monitoring of HDAC–mediated epigenetic regulatory processes …

Europium(Ii)-Containing Complexes For Responsive Magnetic Resonance Imaging, Levi Alexander Ekanger

Wayne State University Dissertations

The research projects described in this dissertation are focused on studying the oxidation of EuII-containing complexes within the context of responsive MRI. Prior to this research, EuII had not been explored within the context of oxidation-responsive MRI nor had the use of this ion been reported in vivo. The results of these studies enable predictions about the oxidation-responsive behavior of EuII-containing complexes in vitro and in vivo.

The EuII-containing cryptate 1.33 was used to evaluate EuII-based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections. The transitory behavior of the positive contrast enhancement correlated with reported levels of oxygenation and …

X-Ray Beam Characteristics And Radiation Dose Deposition To Soft Tissue From Fluoroscopic X-Ray Beams Incorporating Copper Filtration, Kevin Arthur Wunderle

Wayne State University Dissertations

Purpose: This work investigated several topics related to dosimetry in soft tissue from fluoroscopic X-ray beams; first, it investigated the X-ray beam spectra and air kerma rates available for clinical use on state-of-the-art fluoroscopes using spectral (copper [Cu]) filtration; second, it investigated the fluoroscopic X-ray beam characteristics of first half-value layer (HVL), second HVL, homogeneity coefficients (HCs), and backscatter factors (BSFs) across the full range of available beam qualities; and third, it investigated the energy dependence of kerma-area-product (KAP)-meters measuring the radiation output of the fluoroscope. Materials and Methods: A state-of-the-art Siemens Artis Zee fluoroscope was operated in the service …

Oxygen Transport, Shear Stress, And Metabolism In Perfused Hepatocyte-Seeded Scaffolds With Radial Pore Architecture: Experimental And Computational Analyses, Chijioke Mbanu

Wayne State University Dissertations

Several modalities have been proposed as treatments or temporary stop-gap for patients suffering from liver failure until a suitable organ is available. However there is still an urgent need for an off-the-shelf device that can accommodate clinically relevant cell numbers, be cultured at physiological oxygen tensions and, can be fully integrated into and heal the injured hepatic space. In this study we investigated the effects that convective and direct oxygenation had on hepatocyte functionality, morphology and viability while cultured in bulk 3D chitosan scaffolds and perfusion bioreactor systems. Cylindrical chitosan scaffolds with radial directed pore structures were fabricated by a …

Dendrimer Nanoconjugates And Their Oral Inhalation Formulations For Lung Cancer Therapy, Qian Zhong

Wayne State University Dissertations

Lung cancers are leading cause of cancer death for both men and women in the world. Lungs are also one of the primary organs to which almost all cancer can spread. Chemothepray plays a crucial role in the fight against both primary lung cancers and lung metastases. Doxorubicin (DOX) is a potent anticancer drug that has been approved for treating many cancers including lung cancers. However, only a few percent of systemically administered DOX can be found in the lungs. The issue is further complicated by dose-limiting toxicity of DOX. Another major challenge in the use of DOX is its …

Fe3o4 Nanoparticles For Magnetic Hyperthermia And Drug Delivery: Synthesis, Characterization And Cellular Studies, Maheshika Palihawadana Arachchige

Wayne State University Dissertations

In recent years, magnetic nanoparticles (MNPs), especially superparamagnetic Fe3O4nanoparticles, have attracted a great deal of attention because of their potential applications in biomedicine. Among the other applications, Magnetic hyperthermia (MHT), where localized heating is generated by means of relaxation processes in MNPs when subjected to a radio frequency magnetic field, has a great potential as a non-invasive cancer therapy treatment. Specific absorption rate (SAR), which measures the efficiency of heat generation, depends on magnetic properties of the particles such as saturation magnetization (Ms), magnetic anisotropy (K), particle size distribution, magnetic dipolar interactions, and the rheological properties of the target medium.We …

Toward Magnetic Resonance Only Treatment Planning: Distortion Mitigation And Image-Guided Radiation Therapy Validation, Ryan Glen Price

Wayne State University Dissertations

While MR-only treatment planning has shown promise, there are still several well-known challenges that are currently limiting widespread clinical implementation.

Firstly, MR images are affected by both patient-induced and system-level geometric distortions that can significantly degrade treatment planning accuracy. . In addition, the availability of comprehensive distortion analysis software is currently limited. Also while many groups have been working toward a synthetic CT solution, further study is needed on the implementation of synCTs as the reference datasets for linac-based image-guided radiation therapy (IGRT) to help determine their robustness in an MR-only workflow.

A 36×43×2 cm3 phantom with 255 known landmarks …

Sub-Picogram, Inline Detection Of Proteins Using Microfluidic Drop Generators And Shape-Based Detection, Razieh Kebriaei

Wayne State University Dissertations

Proteomic workflows rely on sensitive and precise methods for purifying and detecting proteins, and one of the most popular methods is liquid chromatography (LC) followed by an inline detector. However, the most commonly used method, UV-Vis absorbance, provides relatively low sensitivity and requires long path lengths in the flow cell. In this thesis, we present a highly sensitive, label-free method to detect proteins in continuous flow, using a pressure-driven microfluidic droplet generator. The system consists of a cross junction or flow focusing structure where the flowing stream of proteins is combined with two coflowing streams of oil which break up …

Development Of Scaffold Architectures And Heterotypic Cell Systems For Hepatocyte Transplantation, Dalia Alzebdeh

Wayne State University Dissertations

In vitro assembly of functional liver tissue is needed to enable the transplantation of tissue-engineered livers. In addition, there is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of sizable implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability, an issue which is closely related to the high metabolic rate of hepatocytes. In this study, we first compared two designs of highly porous chitosan-heparin scaffolds seeded with hepatocytes in dynamic perfusion bioreactor systems. The aim …

A Biomechanical Assessment Of Canine Body Armor, Sarah Stojsih

Wayne State University Dissertations

The purpose of this research was to establish a biomechanical assessment of canine body armor with a primary focus on civilian law enforcement canines. The specific aims included: 1) the compilation of canine casualty data to determine commonly reported causes of death/euthanasia while in service for civilian law enforcement canines, 2) the evaluation of the biomechanical response of the canine related to a behind armor blunt impact, 3) the identification of an injury criterion that will best predict canine thoracic injury as a result of behind armor blunt trauma, 4) correlation of the behind armor blunt trauma response to the …

Biomechanical And Biological Evaluation Of A Model Of Post-Traumatic Osteoarthritis Following Noninvasive, Traumatic Rupture Of The Anterior Cruciate Ligament, Tristan Maerz

Wayne State University Dissertations

Post-traumatic osteoarthritis (PTOA) is a prevalent condition following rupture of the anterior cruciate ligament (ACL). While numerous animal models of PTOA exist, most are based on surgical disruption of a stabilizing structure. In the rat, surgical ACL transection is the most commonly employed model, but it may introduce confounding biological factors due to surgery. The purpose of this dissertation was to utilize the tibial compression model of ACL injury to induce a noninvasive ACL rupture in the rat. First, a biomechanical characterization of four different loading protocols was undertaken, and a high-speed, high-displacement protocol was deemed optimal for inducing a …

Frequency Domain Ultrasound Waveform Tomography Breast Imaging, Gursharan Singh Sandhu

Wayne State University Dissertations

Ultrasound tomography is an emerging modality for imaging breast tissue for the detection of disease. Using the principles of full waveform inversion, high-resolution quantitative sound speed and attenuation maps of the breast can be created. In this thesis, we introduce some basic principles of imaging breast disease and the formalism of sound wave propagation. We present numerical methods to model acoustic wave propagation as well methods to solve the corresponding inverse problem. Numerical simulations of sound speed and attenuation reconstructions are used to assess the efficacy of the algorithm. A careful review of the preprocessing techniques needed for the successful …

Quantifying Magnetic Moments And Susceptibilities Of Small Cylindrical And Spherical Objects In Mri, Ching-Yi Hsieh

Wayne State University Dissertations

Purpose: The purpose of this PhD work is to develop a method for accurately quantifying effective magnetic moments and susceptibility of either cylindrical or spherical-like small objects from magnetic resonance imaging (MRI). A standard 3D gradient echo sequence with only one echo time is intended for our approach to measure the effective magnetic moment of a given object of interest. For the quantification of the susceptibility in the cylindrical objects at different orientations, a standard 3D gradient echo sequence with only one or two echo times is needed.

Methods: Our method is to sum over complex MR signals around the …

An Investigation Of The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

Novel Incorportation Of Biomedical Engineering Algorithms (Bispectral Index Guided Or Anesthetic Concentration Guided) In Real-Time Decision Support To Prevent Intraoperative Awareness Using An Electronic Anesthesia Information Mananagement System, Amy Melanie Shanks

Wayne State University Dissertations

Background: Intraoperative awareness with explicit recall (AWR) is a feared complication of surgery that can lead to significant psychological distress. Several large prospective trials have been completed comparing two methods of monitoring anesthetic depth [minimum alveolar concentration (MAC) or electroencephalography (EEG) monitoring using the bispectral index (BIS)] for the prevention of AWR. However, these trials were conducted in high risk populations, limiting generalizability.

Research Hypothesis: Real-time decision support with Anesthesia Information Management System alerts based on a novel anesthetic concentration algorithm (incorporating the use of intravenous anesthetics) or an EEG-guided algorithm will reduce the known incidence of AWR.

Methods: First, …

The Application Of Graphene Films In Biosensing And Electrowetting, Xuebin Tan

Wayne State University Dissertations

In recent years, graphene has been found to possess extraordinary electronic, optical, mechanical and electrochemical properties. Graphene is optically transparent and mechanically flexible, and has high electron mobility and conductivity. In this thesis, we propose to investigate graphene's properties in the detection of biomolecules as well as the manipulation of biological samples. Graphene without defects has high charge carrier mobility and surface areas, which is ideal for biosensors. However, literature shows a lot of variations in the measurements using graphene biosensors. In addition, the surface functionalization of graphene in order to enhance the specificity has not been fully investigated yet. …

Development And Application Of Biomimetic Electrospun Nanofibers In Total Joint Replacement, Wei Song

Wayne State University Dissertations

Failure of osseointegration (direct anchorage of an implant by bone formation at the bone-implant surface) and implant infection (such as that caused by Staphylococcus aureus, S. aureus) are the two main causes of implant failure and loosening. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. A better understanding of the key factors that influence cell fate decisions at the bone-implant interface is required. Our study is to develop a class of "bone-like" nanofibers (NFs) that promote osseointegration while preventing …

Measuring Brain Iron In Healthy Controls And Accessing Venous Abnormalities In Parkinson's Disease Using Mri, Manju Liu

Wayne State University Dissertations

Iron plays a key role in a number of brain cellular processes. However, abnormal brain iron regulation correlates with a number of neurodegenerative diseases such as Parkinson's disease, multiple sclerosis and so forth. To further elucidate the involvement of iron in neurodegenerative disorders, a robust in vivo quantitative non-invasive assessment of normal brain iron deposition over time is essential. A variety of magnetic resonance imaging (MRI) methods have been used to quantify iron both in vivo and in vitro non-invasively. We first created the baseline of phase value and ∆R2^* as a function of age in seven gray matter nuclei. …

High-Performance Accelerometer Based On Asymmetric Gapped Cantilevers For Physiological Acoustic Sensing, Yating Hu

Wayne State University Dissertations

Continuous or mobile monitoring of physiological sounds is expected to play important role in the emerging mobile healthcare field. Because of the miniature size, low cost, and easy installation, accelerometer is an excellent choice for continuous physiological acoustic signal monitoring. However, in order to capture the detailed information in the physiological signals for clinical diagnostic purpose, there are more demanding requirements on the sensitivity/noise performance of accelerometers. In this thesis, a unique piezoelectric accelerometer based on the asymmetric gapped cantilever which exhibits significantly improved sensitivity is extensively studied. A meso-scale prototype is developed for capturing the high quality cardio and …

A Bottom-Up Assembly Of Vascularized Bioartificial Constructs Using Ecm Based Microscale Modules, Ramkumar Tiruvannamalai Annamalai

Wayne State University Dissertations

Tissue engineering aims to create functional biological tissues to treat diseases and damaged organs. A primary goal is to fabricate a 3D construct that can promote cell-cell interaction, extra cellular matrix (ECM) deposition and tissue level organization. Accomplishing these prerequisites with the currently available conventional scaffolds and fabrication techniques still remains a challenge. To reproduce the full functionality there is a need to engineer tissue constructs that mimic the innate architecture and complexity of natural tissues. The limited ability to vascularize and perfuse thick, cell-laden tissue constructs has hindered efforts to engineer complex tissues and organs, including liver, heart and …

Computational Investigation On The Structural Properties Of Neurofilaments And Their Sidearms, Lakshmi Jayanthi

Wayne State University Dissertations

Neurofilaments (NFs) are class IV intermediate filaments, abundantly found in the large myelinated axons. They are the key determinants of axonal diameter and consequently the nerve conduction properties. On the other hand, abnormal NF accumulation has been the hallmark of debilitating neurodegenerative disorders. NF compaction is also one of the pathological manifestations of traumatic axonal Injury. However, the exact relation between the disorganized NFs and the etiology of the neurodegenerative disorders is yet to be fully understood. NFs are assembled from three subunits: Low (NFL), Medium (NFM) and Heavy (NFH). These subunits are characterized by a common alpha helical rod …

Dendrimer Based Nanotherapeutics For Ocular Drug Delivery, Siva Pramodh Kambhampati

Wayne State University Dissertations

PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects.

Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant …

How Atomic Level Interactions Drive Membrane Fusion: Insights From Molecular Dynamics Simulations, Navendu Bhatnagar

Wayne State University Dissertations

This project is focused on identifying the role of key players in the membrane fusion process at the atomic level with the use of molecular dynamics simulations. Membrane fusion of apposed bilayers is one of the most fundamental and frequently occurring biological phenomena in living organisms. It is an essential step in several cellular processes such as neuronal exocytosis, sperm fusion with oocytes and intracellular fusion of organelles to name a few. Membrane fusion is a frequent process in a living organism but is still not fully understood at the atomic level in terms of the role of various factors …

Visual Exploration And Information Analytics Of High-Dimensional Medical Images, Darshan Pai

Wayne State University Dissertations

Data visualization has transformed how we analyze increasingly large and complex data sets. Advanced visual tools logically represent data in a way that communicates the most important information inherent within it and culminate the analysis with an insightful conclusion. Automated analysis disciplines - such as data mining, machine learning, and statistics - have traditionally been the most dominant fields for data analysis. It has been complemented with a near-ubiquitous adoption of specialized hardware and software environments that handle the storage, retrieval, and pre- and postprocessing of digital data. The addition of interactive visualization tools allows an active human participant in …

The Role Of Tissue Sound Speed As A Surrogate Marker Of Breast Density, Mark Sak

Wayne State University Dissertations

Breast density is one of the strongest predictors of breast cancer risk as women with the densest breasts have a three- to five-fold increase in risk compared to women with the least dense breasts. Breast density is currently measured by using mammography, the current gold standard for breast imaging. There are many shortcomings to using mammography to measure breast density, including the use of ionizing radiation. Ultrasound tomography (UST) does not use ionizing radiation and can create tomographic breast sound speed images. These sound speed images are useful because breast density is proportional to sound speed. The purpose of this …

Use Of Focused Ultrasound For Transcranial Sonothrombolysis, Golnaz Ahadi

Wayne State University Dissertations

Worldwide, stroke is the second most common cause of death. Ischemic stroke remains accountable for the majority of the 20 million devastating stroke events occurring globally each year. Use of transcranial focused ultrasound (FUS) for sonothrombolysis is a new research field for ischemic stroke treatment. If shown to be effective, FUS sonothrombolysis could become a widely available treatment option for the majority of the stroke sufferers that do not qualify or do not have access to current thrombolytic treatment options, such as tPA or neurointerventional methods.

The current study was an in vitro transcranial FUS headsystem investigation for the potential …

Imaging Iron Content In Patients With Multiple Sclerosis Using Magnetic Resonance Imaging, Charbel Abdo Habib

Wayne State University Dissertations

The importance of iron in maintaining normal physiological processes in the human body has been well emphasized in the literature. However, "when iron behaves badly", its abnormal presence might lead to a spectrum of pathologies depending on what function has been altered. In the brain, for instance, abnormal iron content is thought to be associated with neurodegenerative diseases. In this dissertation, we study iron involvement in one of the most debilitating neurological diseases, multiple sclerosis (MS), using in vivo magnetic resonance imaging. We first test the sensitivity and specificity of the MR method used, known as susceptibility weighted imaging (SWI) …

Induced Damping And Its Relationship To Beneficial Energy Harvesting In Dielectric Elastomers With Application To Walking, Heather L. Lai

Wayne State University Dissertations

This dissertation presents a novel, interdisciplinary research which addresses the potential of applying soft polymeric materials to strategically harvest biomechanical energy in a beneficial manner for use as a viable, low power source for on-board electronics. Of particular interest are electroactive polymers (EAP), which unlike other types of electromechanical smart materials such as piezoelectric ceramics, which are often brittle, have low elastic modulus and can exhibit large strains without substantial stress generations. One type of EAP, the dielectric elastomer (DE), which utilizes electrostatic forces built up across the dielectric polymer to convert between electrical and mechanical energy, is employed in …

Cervical Spine Tolerance And Response In Compressive Loading Modes Including Combined Compression And Lateral Bending, Daniel Toomey

Wayne State University Dissertations

Injuries in motor vehicle accidents continue to be a serious and costly societal problem. Automotive safety researchers have observed noticeable lateral bending of the anthropomorphic test device (ATD) neck prior to or in conjunction with head impact with the vehicle roof in rollover crash tests. Since there is scant data available about the effects of lateral bending on overall compressive tolerance of the human cervical spine, it is unknown if the presence of lateral bending is important to consider during impacts with the apex of the head. Compressive injury tolerance has historically been reported by identifying the axial force at …

Raman Spectroscopy And Diffuse Reflectance Spectroscopy For Diagnosis Of Human Cancer And Acanthosis Nigricans, Suneetha Devpura

Wayne State University Dissertations

Cancer and diabetes are common chronic diseases in today's world causing numerous deaths in adults as well as children. Most common types of cancers in adults include prostate, lung, breast, colorectal and head and neck squamous cell carcinoma, while among children; leukemia, and brain and central nervous system cancers are quite common. In each of these cases, early detection of the cancer or disease dramatically increases the chances of successful treatment. In recent years, there has been much interest in using Raman spectroscopy and diffuse reflectance spectroscopy as analytical optical spectroscopic methods for early diagnosis of diseases. Raman spectroscopy can …