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  • 1. Cuddington, Clayton Large Scale Synthesis of Polymerized Human Hemoglobin for Use as a Perfusate in Ex Vivo Normothermic Machine Perfusion

    Doctor of Philosophy, The Ohio State University, 2022, Chemical Engineering

    For many people with acute organ failure or genetic conditions such as cystic fibrosis, organ transplantation is the only treatment option. The number of patients on the organ transplant waiting list is over 100,000 with thousands of people on the list dying each year while awaiting a life-saving organ transplant. Traditional organ storage is done using static cold storage (SCS) whereby organ allografts are kept in hypothermic conditions to decrease metabolism and slow tissue death. The harsh ex vivo preservation conditions of SCS mandate a high standard for graft utilization with marginal organs often being discarded for fear of causing graft dysfunction upon transplantation. Normothermic machine perfusion (NMP) represents a method of ex vivo organ preservation to reduce ischemic time and hypothermic organ injury such that grafts are better supported before utilization. NMP has been shown previously to also be able to resuscitate marginal organs that would have otherwise been discarded to be viable for transplantation. A current shortcoming of NMP is the steep oxygen (O2) demand of cellular respiration at normothermia and the metabolic debt acquired by organs during ischemic time post-mortem. To ameliorate this problem, O2 carriers have been used in perfusates; however, there is not yet an optimal O2 carrier for NMP. Red blood cells (RBCs) are prone to hemolysis in ex vivo perfusion and previous commercially available RBC substitutes have had large quantities of cytotoxic low molecular weight (LMW) hemoglobin (Hb) species (<500 kDa). This work describes the scale-up of a next generation polymerized human Hb (PolyhHb) as an RBC substitute in NMP. Previous work in this lab has synthesized a safer PolyhHb with LMW species purified out of solution but had only been made at the bench-top scale. Successfully increasing the process scale to the pilot scale makes this PolyhHb feasible for use in large animal NMP and eventually in clinical trial applications. The (open full item for complete abstract)
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    Committee: Andre Palmer (Advisor); Bryan Whitson (Committee Member); Aleksander Skardal (Other); Jeffrey Chalmers (Committee Member); Sylvester Black (Committee Member) Subjects: Chemical Engineering

  • 2. Duran, Benjamin Development of an Induced Pregnancy Loss Model to Assess the Mechanism of Corpus Luteum Maintenance After Maternal Recognition of Pregnancy in Cattle

    Doctor of Philosophy, The Ohio State University, 2024, Animal Sciences

    The corpus luteum (CL) is required for most of pregnancy in cattle, however, mechanisms governing CL maintenance beyond the period when there is classical maternal recognition of pregnancy (MRP) remain unknown. Recent research findings indicate ~50% of pregnancy loss during the second month of gestation is initiated by CL regression indicating the importance of this mechanism. However, the variability in the incidence and timing of spontaneous pregnancy loss and luteolysis results in significant challenges for evaluating the dichotomy between CL maintenance or regression. Therefore, this dissertation focuses on developing an induced pregnancy loss (IPL) model to elucidate the mechanisms associated with maintenance of the CL beyond the period when there is classical MRP in cattle. The IPL model consists in the induction of conceptus demise through intrauterine administration of hypertonic saline near the onset of the second month of pregnancy. Specific objectives were to: 1) characterize the IPL model in terms of efficacy for inducing conceptus demise, the occurrence and timing of luteolysis, and potential effects on the luteolytic capacity of the endometrium; 2) determine whether prostaglandin F2α (PGF) is responsible for luteolysis after IPL; and 3) assess whether luteolysis after IPL is temporally associated with changes in uterine artery (UA) perfusion. Evaluation of the IPL model, presented in Chapter 2, indicated that infusion of hypertonic saline consistently results in conceptus demise and pregnancy loss regardless of the stage of gestation. Conceptus demise was invariably followed by luteolysis within a predictable time frame, albeit the time of luteolysis was positively associated with the stage of gestation at which conceptus demise was induced. Collectively, these results support the presence of a continuous conceptus-mediated mechanism for CL maintenance beyond the period of MRP. Additionally, intrauterine infusion of hypertonic saline into cyclic cows d (open full item for complete abstract)
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    Committee: Dr. Alvaro Garcia-Guerra (Advisor); Dr. James Kinder (Committee Member); Dr. Douglas Danforth (Committee Member); Dr. Shelia Jacobi (Committee Member); Dr. Joseph Ottobre (Committee Member) Subjects: Animal Sciences

  • 3. Wu, Hao QUANTITATIVE CARDIAC COMPUTED TOMOGRAPHY PERFUSION IMAGING

    Doctor of Philosophy, Case Western Reserve University, 2023, Biomedical Engineering

    Methods for non-invasively assessing coronary artery disease (CAD), the leading cause of mortality and morbidity worldwide, are often inadequate. Among the non-invasive imaging methods, only CT allows one to reliably visualize and quantify the blood vessel lumen using coronary computed tomography angiography (CCTA). My goal is to develop an accurate and practical solution for quantitative cardiac CT perfusion (CCTP). Using CCTA and CCTP, one can identify the presence of an obstructive lesion and directly determine its impact on myocardial blood flow (MBF). In addition, one can uniquely identify low MBF on myocardium and no obstructions in major arteries, indicating the presence of microvascular disease (MVD), a rising concern in cardiology, especially due to its prevalence in diabetes and women. Four projects leading to and using quantitative CCTP are described. First, two scanner-independent, calibration-free, image-based automatic beam-hardening correction algorithms (ABHCs) were developed and compared to other existing correction methods by evaluating artifacts and MBF. Our AHBCs improved the HU value and final MBF estimation results in a digital dynamic anthropomorphic phantom and preclinical porcine experiments that included gold standard virtual mono-energetic images free of beam hardening. Second, the simple linear iterative clustering algorithm with robust perfusion quantification (SLICR) method was developed to reduce the effects of noise and obtain better MBF estimates. In the case of high noise (50% standard x-ray dose level), SLICR improved both standard deviations and means as compared to a singular value decomposition-model independent method with spatio-temporal bilateral filter (101 ± 12 vs. 54 ± 24 mL/min-100g, p < 0.05, actual MBF = 100 mL/min-100g). It gave MBF estimates of 101±6 mL/min-100g for an actual MBF of 100 mL/min-100g, at standard x-ray dose levels and gave estimates resistant to increases in noise. SLICR also greatly reduced computati (open full item for complete abstract)
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    Committee: Satish Viswanath (Committee Chair); Sanjay Rajagopalan (Committee Member); Raymond Muzic Jr (Committee Member); David Wilson (Committee Member) Subjects: Biomedical Engineering

  • 4. Plencner, Eric Stress response of continued intensification of industrial production processes

    Doctor of Philosophy, The Ohio State University, 2022, Chemical Engineering

    This dissertation has three separate areas of focus. In the first, the Heat Shock Protein (HSP) expression of three different Chinese Hamster Ovary (CHO) cell lines is considered. Four different variables are considered to determine if there is an effect to the expression of HSP70 and HSP90. The experiments show a difference in the expression level of HSP between reactors where the air supply is through a ring sparger compared to those where the air supply is through a microsparger. These experiments show far higher variability between days in the microsparger reactor, and we find much greater differences between the highest and lowest point in the microsparger reactors than in the ring sparger reactors. When the reactors used both a ring sparger and a microsparger, eliminating the effect of the poorer Carbon Dioxide removal, we do not see any major difference when compared to the reactors with only a ring sparger. This suggests that the HSP expression difference seen in the microsparger reactor is not due to the stress caused by the smaller bubble, but rather it is due to the higher level of Carbon Dioxide seen in these reactors. When the use of an Alternating Tangential Flow (ATF) perfusion reactor was introduced in the reactor, allowing for the culturing of cells at far higher concentration than in a fed-batch reactor, the HSP expression is much lower than any fed-batch bioreactor, and is far more constant throughout the run than was seen in any fed-batch bioreactor. One set of experiments was performed with a larger scale reactor, 20L fed-batch and 200L perfusion. In these larger scale experiments, we see far lower HSP expression, and far less variability than was seen in the corresponding smaller scale reactor. In the final factor considered, there wasn't any observed difference between the expression level when the feed of a specific growth additive, Cell Boost 4, was varied between reactors. In the HEK cell line, the expression dramatically increas (open full item for complete abstract)
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    Committee: Jeffrey Chalmers (Advisor); David Wood (Committee Member); Eduardo Reategui (Committee Member); Andre Palmer (Committee Member) Subjects: Chemical Engineering

  • 5. Awad, Mohammad Assessment of Pseudo-Continuous Arterial Spin Labeling (pCASL) Inter-Session Reliability in the Quantification of Cerebral Perfusion

    Master of Science (MS), Wright State University, 2019, Anatomy

    Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used for measuring cerebral blood flow (CBF) in a completely non-ionizing and non invasive fashion. ASL is useful in perfusion studies on healthy adult & pediatric subjects, individuals who need multiple follow-ups, and patients with varying cerebrovascular diseases where changes in CBF can be used as an indicator of tissue viability. We used a variation of the ASL technique known as pseudo-continuous ASL (pCASL). This form of ASL is the clinical standard (Alsop et al., 2015). However, it is not well documented the that pCASL is reliable between sessions spanning days to weeks. In this study, we assessed the inter-session reliability of CBF through the use of the pCASL technique. We hypothesize that the pCASL technique can be used to quantify CBF measurements across a 24-hour and 48-hour period. Subjects included 15 healthy, active duty Air Force military personnel recruited by the Wright Patterson Air Force Base from a larger experiment. Of the 15 subjects scanned on day 1 and day 2, 2 did not return for scanning on the third day. All participants were scanned in three identical evening sessions separated by 24 hours. MR imaging was conducted on a 3T MRI scanner with a 24-channel head coil. Each of the iv three days began with a baseline imaging scan followed by sham transcranial direct current stimulation (tDCS) and another identical imaging session. MRI acquisition included a 12-min resting-state function MRI (fMRI), three task fMRI, a T1-weighted MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS) imaging, and resting pCASL. Our work only shows the baseline imaging from each day and the resting pCASL results. Quantitative CBF maps were computed from the raw pCASL data using proton density maps and a single compartment perfusion model through the use of the clinical processing pipeline on the MRI. These CBF maps w (open full item for complete abstract)
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    Committee: Kathrin Engisch Ph.D. (Committee Chair); Matthew Sherwood Ph.D. (Committee Co-Chair); David Ladle Ph.D. (Committee Member) Subjects: Anatomy and Physiology

  • 6. Oommen, Anson Assessing the role of Polyphenols as a vascular protectant against Drug Induced Vascular Injury.

    Master of Science in Biomedical Engineering (MSBME), Wright State University, 2019, Biomedical Engineering

    Vascular injury is identified during pre-clinical toxicity testing within certain pharmacological classes of drug candidates and induces degenerative and hyperplastic changes in endothelial (ECs) and vascular smooth muscle (VSMCs) cells. This drug-induced vascular injury has been show as a side-effect caused by various classes of drugs, including, antibacterial (e.g., azithromycin), anti-malarial (e.g., quinoline), anti-viral (e.g., anti-hepatitis C virus interferons) and nonsteroidal anti-inflammatory drugs (e.g., ibuprofen), and affects normal cardiovascular function and can further lead to various cardiovascular conditions like arrhythmia, cardiac arrest, high blood pressure, and even heart attack. The search for agents capable of reducing vascular injury side-effects by drugs is a very active and important pharmacological field. Dietary polyphenols have been shown to protect the vasculature against drug-induced vascular injury by directly affecting both, VSMCs and ECs. We propose polyphenols like pentagalloyl glucose (PGG), punicalagin and quercetin can be an excellent choice as a vascular protectant against the injury caused by drugs used to treat disease. Our study focusses on the a) development of an ex vivo rat aortic model under a peristaltic flow, and b) testing the vascular protective effects of different polyphenols when our model system is exposed to drugs affecting the vasculature. We will focus on three polyphenols (i.e., PGG, punicalagin, and quercetin) and two drugs (i.e., acetylcholine and phenylephrine). With acetylcholine, known to induce EC-dependent vasodilation, and phenylephrine, known to induced contraction of VSMCs. Result will show the damage caused by drugs on untreated vasculature when compared to those treated with polyphenols.
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    Committee: Jaime Ramirez-Vick Ph.D. (Advisor); Nasim Nosoudi Ph.D. (Committee Member); Amir Zadeh Ph.D. (Committee Member) Subjects: Biomedical Engineering

  • 7. Bush, Michael Patient-specific prospective respiratory motion correction in cardiovascular MRI.

    Doctor of Philosophy, The Ohio State University, 2019, Biomedical Engineering

    Motion in MRI is a significant issue, leading to long scan times and loss of diagnostic quality. Motion in cardiovascular MRI is especially complex, as it contains both respiratory and cardiac motion in addition to general bulk motion. Cardiac motion is effectively gated with an electrocardiogram (ECG) which can bin data into specific cardiac phases, but respiratory motion presents a different challenge due to prohibitively long scan times when data acquisition is limited to end-expiration. Retrospective techniques have been developed to attempt to register frames acquired at varied respiratory phases, but these techniques are limited as they cannot correct for through-plane or exaggerated in-plane motion. Prospective slice tracking has previously been developed to attempt to follow the heart throughout the respiratory cycle, allowing for highly efficient free-breathing imaging. However, these techniques are generally applied with a generic tracking factor to correlate a respiratory signal to the position of the heart, and do not adequately represent the patient and respiratory phase-specific motion of the heart. We have developed a patient and respiratory phase-specific three-dimensional prospective motion correction technique (PROCO) that can model and correct for respiratory motion of the heart in real-time. For each study, a short training scan consisting of a series of single heartbeat images, each acquired with a preceding diaphragmatic navigator, was performed to fit a model relating the patient-specific three-dimensional respiratory motion of the heart to diaphragm position. The resulting motion model was then used to update the imaging plane in real-time to correct for translational motion based on respiratory position provided by the navigator. This model was initially validated by comparing against uncorrected free-breathing (FB), a generic tracking factor of 0.6 (FB-TF), navigator gating (Nav-Gate) and navigator gating combined with a generic trac (open full item for complete abstract)
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    Committee: Orlando Simonetti (Advisor); Rizwan Ahmad (Committee Member); Subha Raman (Committee Member); Ning Jin (Committee Member); Gerhard Laub (Committee Member) Subjects: Biomedical Engineering

  • 8. Levi, Jacob Automated Beam Hardening Correction for Myocardial Perfusion Imaging using Computed Tomography

    Doctor of Philosophy, Case Western Reserve University, 2019, Physics

    Myocardial perfusion imaging using computed tomography (MPI-CT) and coronary computed tomography angiography (CTA) have the potential to make CT an ideal, non-invasive imaging gatekeeper exam for invasive coronary angiography. However, beam hardening (BH) artifacts prevent accurate blood flow assessment and the reduction of false positive identification of coronary disease in MPI-CT. BH occurs when a poly-energetic x-ray beam passes through an attenuating material. Depending on the source spectrum and the material absorption, the low-energy (soft) photons are attenuated at a higher rate than high-energy (hard) photons, therefore hardening the beam. In the image reconstruction process, BH leads to characteristic streaks and non-uniformities (“cupping”), which can lead to incorrect clinical interpretation or diagnosis. Current BH correction methods require either energy-sensitive CT, not widely available, prior knowledge of physical characteristics of the scanner (i.e., the x-ray source spectrum or calibration against attenuating materials). In this dissertation, I propose an image-based, calibration-free, automated BH correction (ABHC) method suitable for MPI-CT, which is one of the most demanding applications for BH correction. In the heart of ABHC, a tailored cost function is used to evaluate streak and cupping artifacts that originate from BH. ABHC minimizes the cost function and finds optimal correction parameters for an image based BH correction algorithm. Two BH correction algorithms from the literature were incorporated into ABHC and tested: the polynomial BH correction and the newer empirical BH correction (EBHC). With both correction algorithms, ABHC leads to optimal correction parameters that dramatically reduced BH artifacts. The ABHC algorithm is evaluated by measuring BH artifact streaks and cupping on simulated and physical phantom images, and on preclinical porcine and clinical MPI-CT data. For example, we observe a reduction of 86% in cupping artifact (open full item for complete abstract)
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    Committee: Michael Martens PhD (Committee Chair); David Wilson PhD (Committee Member); Robert Brown PhD (Committee Member); Steven Izen PhD (Committee Member) Subjects: Biomedical Engineering; Medical Imaging; Physics

  • 9. Kofina, Vrisiis Blood Perfusion and Early Wound Healing Following Implant Placement: A Comparison Between Grafted and Non-Grafted Sites

    Master of Science, The Ohio State University, 2018, Dentistry

    Objective: This study aimed to determine the rate of recovery from surgical trauma through blood perfusion following implant placement surgery and to develop a reliable method to determine volumetric and linear changes within buccal bone following implant placement surgeries using Cone Beam Computed Tomography (CBCT). CBCT-related results were compared with previously used technique to evaluate regenerated bone volume within similar anatomical location. Materials and methods: Patients receiving single non-molar implant in the maxillary esthetic zone were recruited. Data collection was performed at the day of surgery; 3, 6, 9 days; 1 and 4 months, postoperatively. Soft tissue healing was recorded using well-established wound healing parameters during the entire healing period. Wound fluid collected at 3, 6 and 9 days and gingival crevicular fluid (GCF) collected at baseline, 1 and 4 months from the adjacent teeth was used for future multiplex analysis of metabolism mediators. Soft tissue biopsies were collected from the wound site at baseline, 9 days and 4 months and stored for future bone remodeling related gene expression analysis. Buccal flap blood perfusion using Laser Doppler Flowmetry (LDF) was recorded immediately before and after implant placement surgery, at 3, 6, 9 days and, 1 and 4 months. Soft tissue biotype and implant stability quotient (ISQ) were determined at the time of implant placement and at 4 months. Bone thickness changes along the peri-implant buccal wall were evaluated by automatic superimposition of two CBCTs taken immediately after surgery and at 4 months. Peri-implant buccal bone changes along the length of the implant were calculated by using a software. Buccal bone grey values were selected based on soft tissue and bone grey values after automatic superimposition of images. Patients receiving extraction and bone regeneration [socket preservation (SP) or guided bone regeneration (GBR)] within similar anatomical location were recruited. T (open full item for complete abstract)
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    Committee: Binnaz Leblebicioglu (Advisor); Dimitirs Tatakis (Committee Member); Barbaros Selnur Erdal (Committee Member) Subjects: Dentistry

  • 10. Eck, Brendan Myocardial Perfusion Imaging with X-Ray Computed Tomography

    Doctor of Philosophy, Case Western Reserve University, 2018, Biomedical Engineering

    Early detection and treatment of coronary artery disease (CAD) can improve prognosis and overall survival. However, current noninvasive assessment is highly inefficient: of patients referred to invasive angiography, >60% do not have obstructive CAD. Microvascular disease (MVD) accounts for a significant portion of these patients, particularly in patients with diabetes, smoking, hypertension, or other cardiomyopathies. Quantitative estimates of myocardial blood flow by myocardial perfusion imaging (MPI) can detect the physiologic impact of MVD and obstructive CAD. The combination of MPI with computed tomography (MPI-CT) and coronary CT angiography would enable rapid physiologic and anatomic evaluation of CAD and MVD in a single exam. Despite a number of promising MPI-CT reports, the lack of consensus in image acquisition and myocardial blood flow quantification methods, as well as concern regarding imaging artifacts and radiation dose, slows clinical adoption. Four projects are described in this dissertation. First, in a porcine model of flow-limiting stenosis scanned on a spectral detector CT, energy-sensitive reconstruction and dynamic imaging were shown to improve detection of myocardial ischemia as compared to conventional reconstruction and static imaging. Second, the role of imaging conditions and quantification methods was evaluated with regards to obtaining accurate and precise myocardial blood flow (MBF) estimates. Several methods from the literature, some implemented in commercial software, gave imprecise, biased MBF estimates. A proposed robust physiologic model was found to precisely and accurately quantify MBF. Third, a method to calculate MBF confidence intervals (MBFCI) was developed and used to select appropriate analysis models. Use of MBFCI and a goodness-of-fit metric, Akaike Information Criterion (AIC), selected a model with precise MBF estimates whereas AIC alone selected models with imprecise MBF estimates. Fourth, an advanced iterative reco (open full item for complete abstract)
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    Committee: David Wilson PhD (Advisor); Nicole Seiberlich PhD (Committee Chair); Hiram Bezerra MD, PhD (Committee Member); Raymond Muzic Jr., PhD (Committee Member); Steven Izen PhD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Medical Imaging; Radiology

  • 11. Bakaletz, Lauren An investigation of the adherence of Bordetella pertussis to mouse tracheal epithelium in a whole organ perfusion system /

    Doctor of Philosophy, The Ohio State University, 1984, Graduate School

    Committee: Not Provided (Other) Subjects: Biology

  • 12. GIKUNDA, MILLICENT An improved sample loading technique for cellular metabolic response monitoring under pressure

    Master of Science, Miami University, 2016, Physics

    To monitor cellular metabolism under pressure, a pressure chamber designed around a simple-to-construct capillary-based spectroscopic chamber coupled to a microliter-flow perfusion system is used in the laboratory. Although cyanide-induced metabolic responses from Saccharomyces cerevisiae (baker's yeast) could be controllably induced and monitored under pressure, previously used sample loading technique was not well controlled. An improved cell-loading technique which is based on use of a secondary inner capillary into which the sample is loaded then inserted into the capillary pressure chamber, has been developed. As validation, we demonstrate the ability to measure the chemically-induced metabolic responses at pressures of up to 500 bars. This technique is shown to be less prone to sample loss due to perfusive flow than the previous techniques used.
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    Committee: URAYAMA PAUL PROFESSOR (Advisor); VISHWANATH KARTHIK PROFESSOR (Committee Member); BLUE JENNIFER PROFESSOR (Committee Member) Subjects: Biophysics; Physics

  • 13. Warrell, Gregory Computational and Experimental Evaluations of a Novel Thermo-Brachytherapy Seed for Treatment of Solid Tumors

    Doctor of Philosophy, University of Toledo, 2016, Physics

    Hyperthermia has long been known as a radiation therapy sensitizer of high potential; however successful delivery of this modality and integrating it with radiation have often proved technically difficult. We present the dual-modality thermo-brachytherapy (TB) seed, based on the ubiquitous low dose-rate (LDR) brachytherapy permanent implant, as a simple and effective combination of hyperthermia and radiation therapy. Heat is generated from a ferromagnetic or ferrimagnetic core within the seed, which produces Joule heating by eddy currents. A strategically-selected Curie temperature provides thermal self-regulation. In order to obtain a uniform and sufficiently high temperature distribution, additional hyperthermia-only (HT-only) seeds are proposed to be used in vacant spots within the needles used to implant the TB seeds; this permits a high seed density without the use of additional needles. Experimental and computational studies were done both to optimize the design of the TB and HT-only seeds and to quantitatively assess their ability to heat and irradiate defined, patient-specific targets. Experiments were performed with seed-sized ferromagnetic samples in tissue-mimicking phantoms heated by an industrial induction heater. The magnetic and thermal properties of the seeds were studied computationally in the finite element analysis (FEA) solver COMSOL Multiphysics, modelling realistic patient-specific seed distributions. This distributions were derived from LDR permanent prostate implants previously conducted at our institution; various modifications of the seeds' design were studied. The calculated temperature distributions were analyzed by generating temperature-volume histograms, which were used to quantify coverage and temperature homogeneity for a range of blood perfusion rates, as well as for a range of seed Curie temperatures and thermal power production rates. The impact of the interseed attenuation and scatter (ISA) effect on radiation dose distributio (open full item for complete abstract)
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    Committee: Diana Shvydka Ph.D. (Advisor); E. Ishmael Parsai Ph.D. (Committee Member); Victor Karpov Ph.D. (Committee Member); Yanfa Yan Ph.D. (Committee Member); Sorin Cioc Ph.D. (Committee Member) Subjects: Biophysics; Medicine; Physics

  • 14. Fox-Neff, Kristen Inverse Methods in Parameter Estimation for High Intensity Focused Ultrasound (HIFU)

    PhD, University of Cincinnati, 2016, Arts and Sciences: Mathematical Sciences

    High Intensity Focused Ultrasound (HIFU) treatment heats a specified region of tissue to deliver thermal responsive drugs or destroy cancerous tumors noninvasively. To focus HIFU in the desired area, one needs to accurately calculate thermal tissue parameters, an inverse problem. As is the case for tumors located in internal organs, it is difficult to focus HIFU transducers on a target area without heating the surrounding heterogeneous tissue. While average values of tissue parameters are known, values differ from person to person affecting the location, shape and size of the area actually heated from the predicted area significantly unless we account for these individualized parameters. Thus to calibrate the focus of the HIFU, it is important to know individual tissue parameters. In this work we formulate methods to calculate tissue parameters on an individual basis. Additionally we provide bounds on the amount of error expected for each method and analyze how much error in a tissue parameter affects the resulting temperature response. Finally, we present an algorithm that outlines how to combine these individual methods to calculate absorption, thermal conductivity and perfusion in heterogeneous tissue given only the temperature response to an unknown acoustic field.
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    Committee: Benjamin Vaughan Ph.D. (Committee Chair); Donald French Ph.D. (Committee Member); Sookkyung Lim Ph.D. (Committee Member) Subjects: Mathematics

  • 15. Chambers, Andrea Stressed and Strung Out: The Development and Testing of an In Vivo Like Bench-top Bioreactor for the Observation of Cells Under Shear Stress

    Master of Science (M.S.), University of Dayton, 2015, Bioengineering

    Bioreactor systems used for tissue engineering applications are an essential component of understanding the development of new tissues and studying the biochemical interactions between cells and their environment. A bioreactor is typically designed to mimic physiological, environmental, and mechanical stimuli that occur in vivo, and bioreactors are generally created for a specific application, such as for studying 3-dimensional tissues or dynamic fluid flow in 1-dimensional cell monolayers. The leading cause of death in the United States is coronary artery disease, which is treated with bypass graft surgery using a left internal mammary artery or human saphenous vein as the graft. Since human saphenous vein grafts often fail, investigating vascular function as a whole will help to understand more about the method of graft failure. A bioreactor system to study vascular function was successfully developed using the application of endothelial cells under shear stress in a microfluidic slide. The temperature control and diffusion rate of CO2 were recorded inside the bioreactor to confirm the system could stay within a temperature range of 37ºC +/- 0.5ºC and a CO2 concentration between 56,000 ppm and 45,000 ppm. Also, a physiological level of shear stress was determined to be feasible with the peristaltic pump. The performance characteristics of the bioreactor were analyzed, and the apparatus was determined to be successful in generating physiological relevant conditions. Then, human umbilical vein endothelial cells were exposed to both static conditions and venous shear stress conditions for up to four days in an IBIDI® microfluidic chamber. The cell morphology, alignment, and elongation were also evaluated. The cells stayed viable during the duration of all of the dynamic flow experiments, and the cells showed evidence of cell division. The cells were also more aligned and elongated towards the direction of flow for the 48 and 72 hour flow experiments compared to th (open full item for complete abstract)
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    Committee: Robert Wilkens (Advisor); Carissa Krane (Advisor); Kristen Comfort (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Chemical Engineering; Engineering

  • 16. Wright, Katherine Measuring Perfusion with Magnetic Resonance Imaging using Novel Data Acquisition and Reconstruction Strategies

    Doctor of Philosophy, Case Western Reserve University, 2015, Biomedical Engineering

    Tissue perfusion is an important metric that can provide valuable information for disease diagnosis, treatment planning, and treatment follow-up. MRI can quantify perfusion both with and without Gd-based contrast agents, and can provide spatially-localized perfusion maps. However, these techniques are rarely used in the clinical environment. The works in this thesis focused on providing novel data acquisition and/or reconstruction techniques to overcome limitations in DCE MRI and ASL in order to provide clinically-viable perfusion exams. There are three main projects that will be described in this thesis. First, a simultaneous 3D magnetic resonance angiography and perfusion (MRAP) exam is proposed and is demonstrated in the distal lower extremities. Second, a 3D non-Cartesian parallel imaging method is described and used to achieve a low-dose, 3D, high spatiotemporal resolution renal DCE MRI exam that is acquired without breath-holding. Finally, a novel approach to ASL is proposed using the Magnetic Resonance Fingerprinting framework to simultaneously quantify perfusion, transit time, and tissue T1 in a single, efficient acquisition.
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    Committee: Vikas Gulani M.D., Ph.D. (Advisor); David Wilson Ph.D. (Committee Chair); Mark Griswold Ph.D. (Committee Member); Anant Madabhushi Ph.D. (Committee Member); Michael Martens Ph.D. (Committee Member) Subjects: Biomedical Engineering

  • 17. Wang, Hua PART I: FORMATION, PROTEIN MODIFICATION, AND CELLULAR METABOLISM OF 4-HYDROXY-7-OXOHEPT-5-ENOIC ACID LACTONE (HOHA-LACTONE) PART II: DETECTION AND BIOLOGICAL ACTIVITIES OF CARBOXYETHYLPYRROLE (CEP)-PHOSPHATIDYL-ETHANOLAMINE AND METABOLISM OF CEP-LYSINE

    Doctor of Philosophy, Case Western Reserve University, 2014, Chemistry

    Oxidation of phospholipids containing docosahexaenoate leads to the formation of 4-hydroxy-7-oxo-hept-5-enoyl phospholipids (HOHA-PLs) that were previously shown to react with biological primary amines to deliver 2-¿-carboxyethylpyrroles (CEPs), which are novel factors that induce angiogenesis. A spontaneous deacylation product of HOHA-PLs, 4-hydroxy-7-oxo-5-heptenoic acid (HOHA)-lactone, was now found to react with proteins to generate CEPs. An in vitro study found that HOHA-PC forms CEP modifications primarily through initial release of HOHA-lactone followed by reaction of this intermediate with the epsilon-amino group of lysyl residues. These observations, along with the fact that HOHA-lactone was directly produced during lipid oxidation, suggest a novel mechanism of CEP generation in vivo that involves HOHA-lactone as a major intermediate. The metabolism of HOHA-lactone in cells suggests a cellular self-defense system against CEP generation. In a noncytotoxic dose, HOHA-lactone was found to diffuse rapidly into cultured a human retinal pigmented epithelium cell line (ARPE-19) and was metabolized to glutathione adducts and a carboxylic acid derivative, which were then secreted by the cells to extracellular medium. Our study showing that, although it is cytotoxic at high concentration levels, low levels of HOHA-lactone induce RPE cell proliferation and stimulate the secretion of vascular endothelial growth factor (VEGF). These findings suggest that HOHA-lactone plays a role in oxidative stress-induced cell signaling. CEP-derivatives of phosphatidylethanolamines (CEP-PEs) were also found to have proangiogenic effects similar to CEP-protein derivatives. A mass spectrometric assay was developed involving phospholipase D-promoted conversion to a CEP-ethanolamine derivative. The method was applied to the analysis of CEP-PEs in phospholipid extracts of human plasma. Elevated CEP-PE levels were found in plasma from AMD patients compared to plasma from healthy contr (open full item for complete abstract)
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    Committee: Robert Salomon (Advisor); Michael Zagorski (Committee Chair); Gregory Tochtrop (Committee Member); Irene Lee (Committee Member); Henri Brunengraber (Committee Member) Subjects: Analytical Chemistry; Biochemistry; Chemistry

  • 18. Long, Zachary Towards a System for Nanosecond-Gated, Fluorescence Based Monitoring of Cellular Responses to High Hydrostatic Pressures

    Master of Science, Miami University, 2013, Physics

    A time-gated fluorescence spectroscopy system capable of nanosecond gating and picosecond control of gate delays is presented. Used in conjunction with pulsed excitation, the system is capable of tracking the temporal evolution of the fluorescence spectrum from solution samples. The system uses a nitrogen discharge laser as the excitation source and a time-gated intensified CCD detector coupled to a spectrograph. Precise synchronization between the laser pulse and ICCD gate is achieved using a constant-fraction optical discriminator. In addition a high-pressure perfusion system is constructed with an optically compatible high pressure chamber for use in conjunction with fluorescence spectroscopy. System characterizations for both systems are presented, for example, the ability to both spectrally and temporally resolve the content of fluorophore mixtures is confirmed. Time resolved and high pressure perfusion data is collected using Saccharomyces cerevisiae. Biotechnological applications are highlighted, including gated spectroscopy for the real-time monitoring of metabolic activity via measurement of endogenous cellular fluorescence.
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    Committee: Paul Urayama (Advisor); Herbert Jaegar (Committee Member); Stephen Alexander (Committee Member) Subjects: Biophysics; Physics

  • 19. Kalyanaraman, Balaji Bioreactors to Demonstrate Process Automation and Regulate Physiology of Engineered Skin Substitutes

    PhD, University of Cincinnati, 2008, Engineering : Biomedical Engineering

    Engineered skin substitutes (ESS), composed of cultured autologous fibroblasts and keratinocytes inoculated on collagen-glycosaminoglycan (GAG) sponge, are effective adjuncts to split-thickness autograft in the treatment of burns exceeding 50% of total body surface area. The process of ESS fabrication is extremely materials and labor intensive, and these factors contribute to the high cost of the engineered tissue. The use of bioreactors to automate ESS fabrication process has the potential to decrease costs, increase reproducibility, and permit more efficient regulation of ESS anatomy and physiology. In these studies, two bioreactors were evaluated in vitro for their effects on ESS microanatomy, cell viability and proliferation, and barrier formation; and in vivo, by percent original wound area, and percent engraftment after transplantation to athymic mice. ESS fabricated with conventional culture techniques served as controls. The Kerator is a computer controlled bioreactor in which medium changes during keratinocyte culture are fully automated. The growth of keratinocytes on the culture surface of the Kerator, fluroethylene polymer (FEP) film, was compared with that of the polystyrene surface of tissue culture flasks by image analysis for percent confluence. Results indicated that although the confluence was higher in flasks if compared with the Kerator after four days of culture (28±2.3% vs. 18 0.93%), the confluence of keratinocytes in both conditions was similar after six days of culture. The subconfluent keratinocytes were harvested from the Kerator by modifying the method used in conventional keratinocyte culture to reduce trypsinization time. The results of clonal growth assays performed on the keratinocytes harvested from the Kerator demonstrated colony forming efficiencies and growth rate not statistically different from those harvested from flasks (p>0.05). ESS fabricated with keratinocytes harvested from the Kerator were not statistically different from (open full item for complete abstract)
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    Committee: Steven Boyce PhD (Committee Chair); David Butler PhD (Committee Member); Horacio Rilo MD (Committee Member) Subjects: Biomedical Research; Cellular Biology; Engineering; Surgery

  • 20. Kim, Bongsu Multidisciplinary Engineered Approaches to Investigate Human Trabecular Meshwork Endothelial Cells in Regulation of Intraocular Pressure

    Doctor of Philosophy, The Ohio State University, 2011, Biomedical Engineering

    Primary open angle glaucoma (POAG) is the second leading blind disease in the world. The pathological mechanism of glaucoma has been still debated. The general representative symptom of glaucoma is the abnormally increased intraocular pressure (IOP), which causes optic nerve damage and permanent vision loss. According to previous research, the breakdown of production and clearance of aqueous humor (AH) increases the IOP. The specific ocular tissue called as a “trabecular meshwork (TM)” in the AH outflow drainage system is believed to play an important role in the regulation of IOP in the normal range from 15mmHg to 22mmHg. Clinical treatments of glaucoma are to lower the IOP to the normal range. In general, the invasive surgical techniques such as “trabeculectomy”, and “laser trabeculoplasty” are performed with relevant medications. Although the coagulation of tissue by laser based surgeries is less invasive than surgical removal, patients are still exposed to the post-operative risks such as tissue coagulation, inflammation, cornea injury, and cataract. These may cause secondary visual loss. In this work, due to the complex morphology of TM tissue and interrelated parameters involved in the IOP regulation, the key factors governing the outflow facility are investigated using multi-disciplinary approaches. First, the perfusion test was conducted to examine the effect of low fluence diode laser (wavelength: 830nm) which generates the non-invasive level of energy on the hydraulic resistivity of in vitro cultured TM monolayer on the solid porous membrane. The expression of heat shock protein upon low fluence laser treatment was also assessed. The dose-dependent effect of glucocorticoid drug (dexamethasone) was investigated using the electrical impedance spectroscopy. To take into account the three dimensional (3D) porous morphology of TM, polymer based micro/nanofibrous membranes mimicking the in vivo-like environment of natural TM was constructed by combining an arra (open full item for complete abstract)
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    Committee: Yi Zhao PhD (Advisor); Cynthia Roberts PhD (Other); Deborah Grzybowski PhD (Other); Mark Ruegsegger PhD (Other) Subjects: Biomedical Engineering
Release 3.2.12