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  • 1. Mitchell, Robyn Nurse Practitioner Use of Thoracic Pocus Using a Handheld Ultrasound Device in the COVID-19 Pandemic

    DNP, Kent State University, 2021, College of Nursing

    The use of point-of-care ultrasound with a handheld device in the COVID-19 pandemic has several advantages over other imaging modalities. Furthermore, having nurse practitioners who also complete the physical assessment complete point-of-care ultrasound with the handheld device cuts down on the number of providers entering the room. This research project is a single-sample, prospective, cohort design comparing ultrasound findings and diagnoses made by nurse practitioners using point-of-care ultrasound with a handheld device to those made by physicians viewing the same images. Nurse practitioners obtained point-of-care ultrasound images using a handheld device on patients with COVID-19. The images were sent to the physician using the project site email without any patient identification on the images. Physicians independently filled out the same checklist of findings from the ultrasound images and made an independent diagnosis. Concordance between nurse practitioner and physician interpretation of thoracic point-of-care ultrasound images using the handheld device was examined using the Cohen Kappa index. Power analysis was performed using function kappaSize::PowerBinary, finding a minimum population size of 110 needed for a null Cohen kappa value of .62 and an alternative Kappa value of .81. The primary goal of the project was met with a final Cohen kappa of 0.81. Over a three-month period, 98 different patients received POCUS exams with HHU, with a total of 110 exams completed. The Cohen's kappa was 0.81, which represents strong agreement (McHugh, 2012). Implications for the project are adding to the evidence that nurse practitioners are capable of using point-of-care ultrasound and credentialing for nurse practitioners in ultrasound at the project site.
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    Committee: Lisa Onesko (Committee Chair); Louise Knox (Committee Member); Amy Petrinec (Committee Member) Subjects: Nursing

  • 2. Clayson, Keyton Corneal Biomechanical Responses to Intraocular Pressure Using High Frequency Ultrasound Elastography: From Ex Vivo to In Vivo

    Doctor of Philosophy, The Ohio State University, 2019, Biophysics

    The cornea is the clear, front part of the eye, and its shape and transparency are essential for vision. In disease states, including keratoconus and glaucoma, the mechanical properties of the cornea may be altered and could contribute to the progression of eye disease. Current clinical devices cannot measure the mechanical properties of the cornea, but several approaches have been proposed. Most of these approaches either depend on external loading or only provide average responses that cannot delineate where pathologic changes are occurring. In this work, we utilize an ultrasound-based speckle tracking technique to characterize the mechanical response of the cornea during changes in intraocular pressure (IOP) in both ex vivo donor eyes and in living volunteers. The first two studies presented in this work identify how corneal hydration impacts the mechanical response of postmortem cornea. The 3D strain response of porcine corneas during ex vivo inflation testing at two different hydration states (untreated and dextran-treated) were obtained. Our results showed that the dextran-treated corneas showed an inflation response expected of a thin spherical shell, while the inflation response of untreated cornea was confounded with swelling during experimentation. As differences between hydration states were observed, a method was developed to restore and maintain physiological hydration in postmortem corneas during ex vivo experimentation using poloxamer 188 (P188), a synthetic macromolecule surfactant. Our results showed that P188 could return the cornea towards physiological hydration levels after treatment, and that inflation strains were significantly affected by the hydration level of the cornea. These results confirm the impact of hydration state on corneal mechanical response and suggest that P188 treatment may stabilize hydration near physiological levels during ex vivo experimentation. The third study investigated how corneoscleral biomechanical properties (open full item for complete abstract)
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    Committee: Jun Liu (Advisor); Gunjan Agarwal (Committee Member); Cynthia Roberts (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Biophysics; Medical Imaging; Ophthalmology

  • 3. SMITH, DENISE In vitro Characterization of Echogenic Liposomes (ELIP) for Ultrasonic Delivery of Recombinant Tissue-type Plasminogen Activator (rt-PA)

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

    Ultrasound contrast agents (UCAs) stabilized against gas diffusion in the bloodstream yet triggered for destruction by specially designed pulses of ultrasound are desirable for clinical applications in vivo. Echogenic liposomes (ELIP) are nano-sized phospholipid vesicles that contain both gas and fluid. With incorporation of a drug, such as recombinant tissue-Plasminogen Activator (rt-PA), these liposomes may be able to deliver a high local concentration of rt-PA by site-specific delivery of the drug directly to thrombi, with a lower systemic dose overall. Therefore, it is necessary to assess ELIP stability and destruction thresholds in vitro before their application in clinical diagnostic imaging and targeted drug delivery. Several researchers have used optical and acoustic techniques to identify three dominant mechanisms of UCA destruction; static diffusion, acoustically driven diffusion, and fragmentation (Chomas et al, 2001a; Bouakaz et al., 2005; Porter et al., 2006). We have developed new acoustic techniques to assess these three destruction thresholds of an FDA-approved UCA, Optison®, and unmodified ELIP utilizing a clinical diagnostic ultrasound scanner (Porter et al., 2006; Smith et al., 2007a). Recently, in vitro studies were performed with an innovative drug-encapsulated contrast agent, rt-PA-loaded ELIP. Their stability during contrast imaging was assessed using low output B-mode pulses and rt-PA was found to remain associated with the lipid bilayer. They were also fragmented using color Doppler pulses for determination of drug delivery by spectrophotometrically measuring the concentration of rt-PA released (Smith et al., 2007b). The primary objective of this dissertation was to characterize a novel echogenic lipid-based drug-encapsulated UCA using a diagnostic ultrasound scanner for its potential use in both image-guided and ultrasound-triggered drug delivery.
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    Committee: Christy K. Holland PhD (Committee Chair); William S. Ball MD (Committee Member); George J. Shaw MD, PhD (Committee Member); T. Douglas Mast PhD (Committee Member) Subjects: Acoustics; Biomedical Research; Engineering; Health; Pharmaceuticals; Physics; Radiology; Scientific Imaging

  • 4. Reed, Natalie Structural Health Monitoring of Erosion Corrosion Using Passive Ultrasound

    MS, University of Cincinnati, 2024, Engineering and Applied Science: Aerospace Engineering

    A major concern in the oil and gas industry is erosion corrosion which can cause catastrophic failure in pipelines. To monitor and prevent this failure, networks of acoustic emission sensors have been installed on pipelines to detect the presence of abrasive particles in the fluid flow. These abrasive particles damage the inside walls of the pipes through high-velocity impact. It would be advantageous to utilize the ultrasonic transducers in these existing monitoring systems to measure wall thickness. Two main roadblocks exist in utilizing these transducers for wall thickness measurements. First, these systems do not have a way of providing the typical excitation needed for ultrasonic measurements. To combat this issue, this thesis explores two different passive approaches: one that requires no purposeful excitation and another that utilizes acoustic emission from particle impact and fluid flow within the pipe. The second challenge in measuring wall thickness using existing transducers is the frequency range of these transducers which is much lower than what is typically used for ultrasonic time-of-flight thickness measurements. To address this problem, this thesis explores the sensitivity of transducers to the upper limits of their frequency range using a time-of-flight method. Additionally, for thinner-walled components which would require even higher frequencies, a resonant ultrasound spectroscopy method is explored. Experimental measurements using the different measurement modalities and passive excitation approaches are shown using multiple transducers. Several of the experimental combinations tested show good agreement with active measurements and show promise in determining wall thickness.
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    Committee: Joseph Corcoran Ph.D. (Committee Chair); Francesco Simonetti Ph.D. (Committee Member); Gui-Rong Liu Ph.D. (Committee Member) Subjects: Aerospace Engineering

  • 5. Biehl, Sarah Optimized Classification of Accurate and Misarticulated Rhotic Speech Sounds for Use in a Gamified Real-time Ultrasound Biofeedback System

    MS, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

    The use of ultrasound in speech therapy provides real-time visual feedback of tongue movement during speech. Ultrasound is a therapeutic tool for treating sounds with complex articulatory patterns and diverse populations, including individuals with speech sound disorders, hearing impairments, childhood apraxia of speech, and speech errors following a stroke. The benefits of ultrasound biofeedback therapy (UBT) for remediating speech deficits could be enhanced by integrating UBT into a real-time, gamified interface that provides real-time articulatory feedback and promotes an external focus of attention, reducing the complex cognitive demands required for standard UBT. Previous studies have shown that accuracy of American English rhotic /r/ can be predicted by a single parameter, d, the difference between tongue dorsum and blade displacements measured by ultrasound imaging during speech production. This parameter has classified speech productions of rhotic syllables as correct versus misarticulated with a classification accuracy up to 85%. However, implementation of this classification approach into real-time gamified UBT, including both measurement timing and establishment of difficulty levels for progressive therapy, would benefit from optimization that is clinically relevant to real-time gamified UBT and uses a larger dataset than previously analyzed. 2,300 productions of 10 distinct rhotic syllables (including prevocalic and postvocalic contexts) from 49 children, with and without speech errors, were analyzed. For each production, ultrasound image sequences were processed by TonguePART software to acquire tongue displacement trajectories, and accuracy was judged by trained listeners using a visual analog scale (VAS). For each syllable, receiver operating characteristic (ROC) curve analyses using an 8-fold cross validation method were conducted to optimize selection of the image frame approach for classification using the d parameter and determine parameter thresh (open full item for complete abstract)
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    Committee: T. Douglas Mast Ph.D. (Committee Chair); Michael Riley Ph.D. (Committee Member); Kevin Haworth Ph.D. (Committee Member); Suzanne Boyce Ph.D. (Committee Member) Subjects: Biomedical Research

  • 6. Kwok, Sunny Applications of ex vivo and in vivo ultrasound imaging techniques for the characterization of cornea, retina, sclera, and optic nerve head biomechanics

    Doctor of Philosophy, The Ohio State University, 2023, Biomedical Engineering

    The biomechanical properties of the eye can be directly linked to ocular health and likely play a role in the pathogenesis of ocular diseases and the eventual loss of vision. Altered biomechanics in the corneal stroma at the front of the eye are implicated in the progression of corneal ectasia. Mechanical and downstream biochemical factors in the sclera and optic nerve head are suspected to cause optic neuropathy. To maintain structural support and proper ocular function in the eye, the ocular shell must balance both internal and external stresses and strains. The exact nature of the biomechanical contributions in ocular diseases remains unclear and warrants further study. The goal of this work is to evaluate ocular structure biomechanics using high-frequency ultrasound elastography both in ex vivo globes and in vivo subjects. Insights into the behavior of ocular tissue may uncover new therapeutic targets for the diagnosis, monitoring, and treatment of ocular pathologies. The first study presented in the following work characterized the through-thickness corneal stromal deformations in human globes (from both normal and keratoconus, KC, donors) during ex vivo IOP elevation using high-frequency ultrasound elastography. Our results showed consistent strain responses across the normal corneas. In KC eyes, we observed similar overall strains as in normal eyes but marked regional heterogeneity and large strains in the characteristic cone region. These findings suggested regional variation of mechanical responses to IOP elevation in both normal and KC corneas, and KC appeared to be associated with mechanical weakening in the cone region. These results suggested that high-frequency ultrasound elastography has the resolution to spatially resolve KC regional biomechanics. The next three studies developed, implemented, and validated a novel in vivo ultrasound technique to measure corneal deformations induced by the intrinsic ocular pulse, termed ocular pulse elastography (O (open full item for complete abstract)
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    Committee: Jun Liu (Advisor); Matthew Reilly (Committee Member); Cynthia Roberts (Committee Member) Subjects: Biomedical Engineering

  • 7. Cooley, Michaela Nanobubble Ultrasound-Contrast Agents as a Strategy to Assess Tumor Microenvironment Characteristics and Nanoparticle Extravasation

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

    In many chronic inflammatory diseases, the vascular endothelium becomes pathologically permeable due to conditions like angiogenesis and production of growth factors and inflammatory cytokines (e.g., histamine, bradykinin, etc.). In cancer, this process can be exploited for delivery of nanoparticles to tumors via the enhanced permeability and retention (EPR) effect. However, nanoparticle-based therapeutics reliant on the EPR effect have led to inconsistent results in patients. This is due to many factors, with a significant one being heterogeneous tumor vascular architecture and morphology both between patients and within a single tumor. Transport of the nanoparticle to the tumor and into the parenchyma is complicated by uptake by the immune system, ineffective margination, and inefficient extravasation. Guidance is needed to inform clinicians on what therapies may be most effective for each patient. Effective guidance could reduce health-care costs and negative side effects of medication. An inexpensive, safe, non-invasive, and real-time imaging method that has high temporal and spatial resolution may be capable of categorizing the extent of vascular permeability in tumors and once validated, personalize therapeutic regimens for patients. Such a tool could be used not only for tumors, but for all diseases involving pathologically permeable vasculature. With this goal in mind, the objective of this thesis is to work toward development of a real-time method for evaluating vascular permeability over the entire tumor using novel nanobubble (NB)-based contrast-enhanced ultrasound (CEUS). This work builds upon dynamic CEUS protocols used clinically with microbubbles (MBs). NBs, which are 100-400 nm in diameter, are approximately 10x smaller than MBs and have been shown to extravasate into the tumor interstitium. To reach the final objective of this work, NB dynamics from intravenous injection to retention in the tumor must be studied. To this aim, in vitro studies con (open full item for complete abstract)
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    Committee: Agata Exner (Advisor); Horst von Recum (Committee Chair); Anirban Sen Gupta (Committee Member); Aaron Proweller (Committee Member) Subjects: Biomedical Engineering; Medical Imaging; Medicine; Nanoscience; Nanotechnology; Oncology; Radiology

  • 8. Grimm, Peter Real-time Control of Radiofrequency Thermal Ablation using Three-dimensional Ultrasound Echo Decorrelation Imaging Feedback

    MS, University of Cincinnati, 2022, Engineering and Applied Science: Electrical Engineering

    Liver cancer is a significant public health burden; as of 2020, it is the second leading cause of cancer-related mortality worldwide. Hepatic resection is considered the gold standard for the treatment of liver malignancies. However, this procedure is only possible in a minority of patients, necessitating treatment modalities with comparatively worse performance, such as thermal ablation. Thermal ablation generally results in poorer clinical outcomes relative to resection, with a higher rate of recurrence and the potential for complications related to damage to healthy tissue near the ablation zone. Medical imaging techniques can improve thermal ablation procedures via assistance in preoperative planning, probe placement and postoperative evaluation, but clinicians lack a method to monitor and control thermal ablation while the procedure is ongoing. Echo decorrelation imaging is a pulse-echo ultrasound imaging technique that measures stochastic variations in echo signals arising from thermal treatment. The method has been shown to accurately predict thermal lesioning in in vivo and ex vivo studies of thermal ablation using conventional 2D ultrasound imaging. This thesis aims to apply the echo decorrelation methodology to volumetric ultrasound data to control RFA procedures in real-time. Feedback control is implemented as a bang-bang type controller that automatically stops thermal treatment if the spatial mean of the cumulative decorrelation map exceeds a set threshold. 3D echo decorrelation-based control was evaluated through a series of feedback- controlled and uncontrolled ablation trials on ex vivo bovine liver tissue using a clinical RFA system. The RFA system was set to target a 15 mm radius spherical region of tissue while decorrelation maps were computed from captured volumetric ultrasound data; if the control criterion was met, the procedure was automatically stopped using a custom- designed microcontroller circuit. Trials were divided into two groups (open full item for complete abstract)
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    Committee: T. Douglas Mast Ph.D. (Committee Member); Xuefu Zhou Ph.D. (Committee Member); Mehdi Norouzi Ph.D. (Committee Member) Subjects: Radiology

  • 9. Nittayacharn, Pinunta ULTRASOUND-MEDIATED DRUG-LOADED NANOBUBBLES AS A THERANOSTIC AGENT FOR OVARIAN CANCER TREATMENT

    Doctor of Philosophy, Case Western Reserve University, 2021, Biomedical Engineering

    Issues with limited intratumoral drug penetration and heterogeneous drug distribution continue to impede the therapeutic efficacy of nanomedicine-based delivery systems, especially in metastatic disease. Ultrasound (US)-mediated drug delivery has emerged as one of the most effective means of overcoming these challenges. An enhancement of vascular permeability and on demand drug release can be triggered by physical US effects including cavitation, acoustic streaming, or hyperthermia caused by pressure variation of acoustic wave. Microbubbles (MBs) have been widely used as a drug-carrier for cancer theranostics. However, their clinical application in drug delivery is limited by their large size (1-8 um). Alternatively, submicron echogenic bubbles or nanobubbles (NBs) with size of 100-500 nm, can promote extravasation by taking an advantage of the enhanced permeability and retention (EPR) effect, resulting in higher drug accumulation in tumors and improved efficacy. The overall goal of the research described in this dissertation is to develop a more effective US-mediated drug delivery system to improve treatment efficacy for patients diagnosed with early or advanced ovarian cancer. An optimal NB formulation with a highly stable NB and high drug loading was developed and characterized in vitro. An effective strategy to improve drug loading efficiency into the bubbles using deprotonation technique was used. Delivery efficiency and therapeutic efficacy of these NBs were evaluated in cell culture model of human cancer cells. Improved in vitro therapeutic efficacy of these drug-loaded NBs in human ovarian cancer cells (OVCAR3) was observed. To further understand the in vitro and in vivo behavior and stability of these NBs, the influence of size and concentration of the NBs were investigated. Lastly, the optimized NB formulation and delivery parameters were used to treat orthotopic rat liver tumors which was selected as an aggressive cancer model. Accumulation of drug and NB (open full item for complete abstract)
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    Committee: Anirban Sen Gupta (Committee Chair); James Basilion (Committee Member); Jeffrey Capadona (Committee Member); Agata Exner (Advisor) Subjects: Biomedical Engineering; Biomedical Research; Nanotechnology

  • 10. Pashaei, Vida Flexible Body-Conformal Ultrasound Systems for Autonomous Image-Guided Neuromodulation

    Doctor of Philosophy, Case Western Reserve University, 0, EECS - Electrical Engineering

    The interest in acoustic neuromodulation, which relies on the use of low-intensity focused ultrasound (FUS) to stimulate or inhibit neural networks, has rapidly increased due to its potential for non-invasive, portable, and low-cost treatment of various neurological disorders with sufficient spatial resolution and penetration depth. For example, the possibility of using FUS for vagus or tibial nerve modulation has the potential to provide effective treatment of disorders such as epilepsy, potentially chronic heart failure, and psychiatric conditions while avoiding the well-known side effects of implanted modulation electrodes, which include voice alterations and dyspnea. However, current FUS systems have several drawbacks limiting their broad application. First, current systems lack an integrated, portable, and low-cost imaging system with enough resolution to find the appropriate position and focal depth for modulation. Second, the relative size, weight, and power (SWaP) of current systems are restrictive for broad adoption. Third, a highly trained technician is required to control the position and angle of the ultrasound probe and to analyze the images produced by these systems. Fourth, there is high variability among users making ultrasound imaging and modulation challenging for broader use. In this work, the design and implementation of a flexible body-conformal ultrasound system for closed-loop image-guided acoustic neuromodulation are presented. The system uses ultrasound for localization and focused modulation of a specific neural system. The developed ultrasound probe integrates two flexible sub-arrays of ultrasound transducers within a single lightweight, wearable device. A 16-element array of piezoelectric transducers is developed for focused modulation of the nerve, and a second 64-element array is integrated on the probe for neural imaging and localization. Subsequently, an active version of the flexible probe is developed, including solid-state switc (open full item for complete abstract)
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    Committee: Soumyajit Mandal (Advisor); Christian Zorman (Committee Member); Mahdi Bayat (Committee Member); Agata A. Exner (Committee Member); Steve Majerus (Committee Member) Subjects: Acoustics; Biomedical Engineering; Electrical Engineering; Health Care; Medical Imaging; Neurosciences; Radiology; Systems Design

  • 11. Goodman, Garrett Design of a Novel Wearable Ultrasound Vest for Autonomous Monitoring of the Heart Using Machine Learning

    Doctor of Philosophy (PhD), Wright State University, 2020, Computer Science and Engineering PhD

    As the population of older individuals increases worldwide, the number of people with cardiovascular issues and diseases is also increasing. The rate at which individuals in the United States of America and worldwide that succumb to Cardiovascular Disease (CVD) is rising as well. Approximately 2,303 Americans die to some form of CVD per day according to the American Heart Association. Furthermore, the Center for Disease Control and Prevention states that 647,000 Americans die yearly due to some form of CVD, which equates to one person every 37 seconds. Finally, the World Health Organization reports that the number one cause of death globally is from CVD in the form of either myocardial infarctions or strokes. The primary ways of assisting individuals affected with CVD are from either improved treatments, monitoring research, or primary and secondary prevention measures. In the form of cardiovascular structural monitoring, there are multiple ways of viewing the human heart. That is, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Computed Tomography (CT), and Ultrasonography are the four fundamental imaging techniques. Though, continuous monitoring with these imaging techniques is far from currently possible. Large financial cost and size (MRI), radiation exposure (PET and CT), or necessary physician assistance (Ultrasonography) are the current primary problems. Though, of the four methodologies, Ultrasonography allows for multiple configurations, is the least expensive, and has no detrimental side effects to the patient. Therefore, in an effort to improve continuous monitoring capabilities for cardiovascular health, we design a novel wearable ultrasound vest to create a near 3D model of the heart in real-time. Specifically, we provide a structural modeling approach specific to this system's design via a Stereo Vision 3D modeling algorithm. Similarly, we introduce multiple Stochastic Petri Net (SPN) models of the heart for future functiona (open full item for complete abstract)
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    Committee: Nikolaos G. Bourbakis Ph.D. (Advisor); Soon M. Chung Ph.D. (Committee Member); Yong Pei Ph.D. (Committee Member); Iosif Papadakis Ktistakis Ph.D. (Committee Member); Konstantina Nikita Ph.D. (Committee Member); Anthony Pothoulakis M.D. (Other) Subjects: Biomedical Engineering; Biomedical Research; Computer Science; Medical Imaging

  • 12. Hernandez, Christopher Stabilized Nanobubbles for Diagnostic Applications

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

    Bulk nanobubbles, also known as ultrafine bubbles (ISO/ TC281), have recently gained the interest of the research community for their potential application as ultrasound contrast agents for molecular imaging and cancer therapy. However, even with this growing interest, the very existence of nanobubbles and their use as contrast agents have been a subject of controversy for over a decade. This is due to the theoretical effect of reducing the bubble diameter to the nanoscale on both its Laplace pressure and resonance frequency leading to instability and reduced imaging quality, respectively. Despite these theoretical limitations, we have developed a stable and echogenic nanobubble formulation through incorporation of Pluronic, a nonionic triblock co-polymer surfactant, into the lipid shell of perfluorocarbon gas bubbles. To further understand the biophysical properties of these novel nanobubbles, we explored factors contributing to their echogenicity, stability, and fate after gas dissipation. Bubbles were confirmed to be in the sub-micron range and produced strong contrast at clinical ultrasound frequencies. Additionally, it was demonstrated that the incorporation of Pluronic into the lipid membrane increases the stability of nanobubbles under ultrasound by decreasing its monolayer surface tension. Due to the strong interest in the use of nanobubbles as drug delivery agents, their ultimate fate when destroyed by high-power ultrasound was investigated using cryo-EM. Lastly, as a proof of study, CA-125 and PSMA-targeted nanobubbles were developed for the detection of ovarian and prostate cancer, respectively. Results demonstrated that nanobubbles can be used to target and reach antigens expressed on cancer cells beyond the tumor vasculature. Characterization and optimization of nanobubble properties achieved the creation of novel, stabilized nanobubbles for numerous potential clinical applications.
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    Committee: Agata Exner Ph.D. (Advisor); Horst von Recum Ph.D. (Committee Chair); James Basilion Ph.D. (Committee Member); Dean Nakamoto M.D. (Committee Member) Subjects: Biomedical Engineering

  • 13. Huang, Shenwen The Effect of 120-kHz Ultrasound on Thrombolytic Efficacy in Porcine Thromboembolism Models

    PhD, University of Cincinnati, 2017, Engineering and Applied Science: Biomedical Engineering

    Ischemic stroke affects nearly 700,000 patients in the United States each year and is the fifth most common cause of death. In less than 6% of ischemic stroke patients, lysis of the occlusive clot is attempted with recombinant tissue-plasminogen activator (rt-PA). The addition of Definity® microbubbles and 120-kHz ultrasound to rt-PA treatment has been shown to enhance lytic activity in vitro and ex vivo. However, preclinical trials must be completed in an animal model such as pigs prior to human clinical trials. One porcine thrombosis model is the intracerebral hemorrhage model, in which an intracerebral hemorrhage is treated with a lytic and exposed to ultrasound. An assay for a biochemical marker of clot breakdown, D-dimer, was evaluated for quantification of thrombolysis in this model. A porcine D-dimer purification protocol was developed and the identity of the purified D-dimer was confirmed by immunoblotting and MALDI TOF-TOF analysis. We evaluated a commercially available D-dimer ELISA kit and 5 commercially available D-dimer antibodies for development of an in-house ELISA protocol. In porcine samples produced in an in vitro thrombolysis system, D-dimer concentration was shown to correlate with mass loss. However, no current assay is known to be able to quantitate D-dimer with adequate sensitivity (10 ng/mL). To create an arterial thromboembolism model of ischemic stroke, porcine ascending pharyngeal arteries (APA) were occluded bilaterally. Most arteries were occluded with a single clot chosen to be about 1 mm larger than the inner diameter of the target artery. However, intraarterial treatment of the occluded arteries with rt-PA was ineffective and did not recanalize any of the occluded arteries. A protocol for post-mortem APA excision from swine was also developed. The lack of rt-PA efficacy in the porcine arterial thromboembolism model suggested that porcine clots were resistant to rt-PA thrombolysis. In vitro evaluation of the lytic response o (open full item for complete abstract)
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    Committee: Christy Holland Ph.D. (Committee Chair); Todd Abruzzo Ph.D. (Committee Member); Kevin Haworth Ph.D. (Committee Member); Andrew Herr Ph.D. (Committee Member); Daria Narmoneva Ph.D. (Committee Member) Subjects: Biomedical Research

  • 14. Daftardar, Saloni Ultrasound-mediated Topical Delivery of Econazole nitrate for Treating Raynaud's Phenomenon

    Master of Science in Pharmaceutical Science (MSP), University of Toledo, 2017, Pharmaceutical Sciences (Industrial Pharmacy)

    Objectives: The focus of this investigation was to assess the ultrasound-assisted econazole nitrate (EN) permeation from topically applied formulations for treating Raynaud's phenomenon. The aims of this study were i) to identify the optimal ultrasound parameters for the percutaneous absorption of EN, ii) to assess the in vitro percutaneous absorption of EN and toxicity in the porcine ear skin from different topical formulations following ultrasound application. Methods: Optimization of ultrasound parameters such as the distance of the horn, application time and amplitude were performed. In vitro percutaneous absorption studies were performed using different EN formulations (F1_solution, F2_HPMC dispersion, F3_Lipoderm® Activemax™ Cream and F4_Versabase® cream) across ultrasound-treated porcine skin and were compared with the control group (skin samples without ultrasound treatment). Histological evaluation using hematoxylin and eosin stain was carried out to assess the dermal toxicity of formulations and ultrasound exposure. To further support the findings of ultrasound-assisted drug permeation studies, ATR-FTIR was performed to investigate the effect of ultrasound on the conformational changes in stratum corneum lipids characterized by the changes in spectral shifts. Results: A constant frequency (20 kHz) ultrasound application with 40% amplitude, 0.5cm distance between ultrasound horn and skin surface for 2 minutes was optimized. The permeation of EN was found to be higher from ultrasound- treated skin samples than the control group. Drug permeation from F2_HPMC dispersion was found to be higher as compared to other formulations and the marketed cream. The lag time of ultrasound- treated skin samples were found to be significantly lower than the control. Histological evaluation confirmed that HPMC dispersion showed no signs of toxicity. ATR-FTIR studies revealed a slight increase in the -CH2- stretching vibrations (~ 2920 cm-1 and 2850 cm-1) in ultrasound-t (open full item for complete abstract)
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    Committee: Sai HS Boddu PhD (Committee Chair) Subjects: Pharmaceuticals; Pharmacy Sciences

  • 15. Fosnight, Tyler Echo Decorrelation Imaging of In Vivo HIFU and Bulk Ultrasound Ablation

    MS, University of Cincinnati, 2015, Engineering and Applied Science: Biomedical Engineering

    Echo decorrelation imaging, a pulse–echo method that maps heat-induced changes in ultrasound echoes, was investigated for in vivo monitoring of thermal ablation in a liver cancer model. In open surgical procedures, rabbit liver with implanted VX2 tumor were imaged by image-ablate arrays and treated with bulk ultrasound (unfocused) ablation (N=10) or high-intensity focused ultrasound (HIFU) (N=13). Echo decorrelation and integrated backscatter (IBS) images were formed from pulse-echo images recorded during rest periods following each sonication pulse. Echo decorrelation images were corrected for motion- and noise-induced artifacts using measured echo decorrelation from corresponding sham trials. Sectioned ablated tissue was vitally stained with triphenyl tetrazolium chloride (TTC) and binary images were constructed based on local TTC staining. Analysis was performed for the focused exposures, unfocused exposures and for all exposures combined. Motion correction significantly reduced echo decorrelation in non-ablated liver regions. The reduction was significant in non-ablated VX2 tumor regions for focused exposures and all exposures combined. The reduction was not significant in ablated VX2 tumor regions for unfocused exposures. Echo decorrelation reduction was marginally significant in ablated regions for focused and unfocused exposures and was significant for all exposures combined. Prediction of ablation by echo decorrelation and IBS imaging was assessed using receiver operating characteristic (ROC) curves. Areas under the ROC curve (AUC) were significantly greater than chance for ablated liver prediction by corrected echo decorrelation and IBS. Echo decorrelation did not predict ablated VX2 tumor significantly better than chance for focused exposures. IBS did not predict ablated VX2 tumor better than chance for focused exposures and unfocused exposures. Corrected echo decorrelation predicted ablated liver significantly better than IBS for the focused exposu (open full item for complete abstract)
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    Committee: T. Douglas Mast Ph.D. (Committee Chair); Syed Arif Ahmad M.D. (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Biomedical Research

  • 16. Salgaonkar, Vasant Passive Imaging and Measurements of Acoustic Cavitation during Ultrasound Ablation

    PhD, University of Cincinnati, 2009, Engineering : Biomedical Engineering

    Cavitation is known to affect therapeutic ultrasound applications such as tissue ablation, where it may complicate heat deposition and make treatment control difficult. In this thesis, acoustic emissions from cavitating bubbles are measured and imaged to serve as indicators of thermal ablation progress. Cavitational acoustic emissions were measured using a 1-MHz transducer during thermal ablation of excised bovine livers with a 32-element linear array (3.1 MHz, 0.8-1.4 MPa pressure amplitude). Broadband, subharmonic and low-frequency emissions consistent with inertial, stable and vaporous cavitation respectively were observed. Broadband (r = 0.848) and low-frequency (r = 0.747) emissions exhibited statistically significant linear correlations with coagulated tissue volumes. Statistical models based on multinomial logistic regression were implemented to predict tissue temperature based on measured cavitational emission signals.To perform spatially sensitive measurements of cavitation activity, images were created from beamformed bubble emission signals received by a diagnostic imaging array. This method was called passive cavitation imaging. Analytic models for point spread functions were developed to test this imaging method. It was implemented on a 192-element linear array (7.5 MHz) and separate images of stable and inertial cavitation activity were created in free field and tissue media, with mm-level resolution along the array azimuth. Passive cavitation imaging techniques were used to record emissions during ablation of ex vivo bovine liver with 1.1-MHz (1984 W/cm2 focal intensity) focused ultrasound. Spatial correspondence was observed between harmonic emissions and tissue lesioning, along the array azimuth. This was assessed by a statistically significant correlation (r = 0.684) and area under a receiver operating characteristics (ROC) curve (AUROC = 0.71).The present cavitation detection and imaging techniques, implemented in this thesis to monitor ultrasound (open full item for complete abstract)
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    Committee: T. Douglas Mast PhD (Committee Chair); Christy Holland PhD (Committee Member); Marepalli Rao PhD (Committee Member) Subjects: Biomedical Research

  • 17. DATTA, SAURABH The Role of Cavitation in Enhancement of rt-PA Thrombolysis

    PhD, University of Cincinnati, 2007, Engineering : Biomedical Engineering

    Pulsed ultrasound, when used as an adjuvant to a thrombolytic, such as recombinant tissue plasminogen activator (rt-PA), could enhance therapeutic efficacy. Such enhancement would represent a significant breakthrough in the treatment of diseases like ischemic stroke, myocardial infarction, pulmonary embolism and deep vein thrombosis. Acoustic cavitation was hypothesized in this work to be the underlying mechanism responsible for thrombolytic enhancement. Existing theoretical models were employed to predict rectified diffusion and cavitation thresholds at 120 kHz. Stable and inertial cavitation thresholds were measured experimentally and clots were exposed to cavitational activity in the presence of rt-PA. Subsequently, an approach for cavitation nucleation using infusion of a contrast agent was tested experimentally in vitro. Finally, a technique for stable cavitation monitoring was developed which tracks the ultraharmonic emissions during the combined ultrasound and thrombolytic exposures in a human blood clot model. The stable cavitation activity was measured during clot mass loss experiments. A dual antibody immunofluorescence technique was employed to measure penetration depths of rt-PA and plasminogen into the clots. Porcine whole blood clots, when exposed to stable cavitation activity in the presence of rt-PA, resulted in the highest mass loss of 26.0 ± 4 %. The presence of inertial cavitation lowered the mass loss to 20.7 ± 1.6 %. A commercial contrast agent, Definity®, was successfully used to promote and sustain the nucleation of stable cavitation during pulsed ultrasound exposure at 120 kHz for 30 min. The largest clot mass loss of 26.2 ± 2.6 % was observed in human whole blood clots in the presence of sustained stable cavitation activity. A significant correlation was observed between clot mass loss and ultraharmonic signals (r=0.8549, p<0.0001, n=24). The largest mean penetration depth of rt-PA (222 µm) and plasminogen (241 µm) was observed in the presen (open full item for complete abstract)
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    Committee: Dr. Christy Holland (Advisor) Subjects:

  • 18. Tang, Junhua Ultrasonic Characterization of Corneal and Scleral Biomechanics

    Doctor of Philosophy, The Ohio State University, 2012, Biomedical Engineering

    Cornea and sclera are the major load-bearing tissue of the eye and the biomechanics of the cornea and sclera have been shown to be critical in the understanding, diagnosis and management of glaucoma. It is therefore important to non-invasively measure the mechanical properties of the cornea and sclera and examine their effects in glaucoma. The current study was designed to investigate the effect of corneal stiffness on intraocular pressure (IOP) and central corneal thickness (CCT) measurements and develop ultrasound-based techniques for non-invasive characterization of corneal and scleral biomechanics under physiological loadings and configurations. We first examined the effect of the natural variation in speed of sound in cornea on the measurement of corneal thickness, which is an important parameter affecting the IOP measurement and a risk factor of glaucoma. The effect of the variation in corneal stiffness on IOP measurement was examined experimentally, and a non-invasive ultrasound method for measuring acoustic impedance was used to estimate the corneal stiffness and potentially provide corrections for IOP measurement. An ultrasound strain imaging method based on speckle tracking was developed to characterize the mechanical response of the sclera under IOP elevations, and the performance of the ultrasound method was evaluated both experimentally and using simulations. The mechanical responses of the porcine and human sclera under IOP elevations were then examined by this ultrasound strain imaging method. The variance of speed of sound in cornea was shown to potentially produce significant error in corneal thickness measurement using the current clinical setting of speed of sound in ultrasound pachymetry. Corneal acoustic impedance was significantly correlated with the speed of sound in cornea and could potentially be used to improve corneal thickness measurement accuracy. The effect of corneal stiffness on IOP measurement was found to be significant, and the co (open full item for complete abstract)
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    Committee: Jun Liu PhD (Advisor); Richard Hart PhD (Committee Member); Paul Weber MD (Committee Member); Cynthia Roberts PhD (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Ophthalmology

  • 19. Chandrana, Chaitanya Development of A Focused Broadband Ultrasonic Transducer for High Resolution Fundamental and Harmonic Intravascular Imaging

    Doctor of Engineering, Cleveland State University, 2008, Fenn College of Engineering

    Intravascular ultrasound (IVUS) is increasingly employed for detection and evaluation of coronary artery diseases. Tissue Harmonic Imaging provides different tissue information that could additionally be used to improve diagnostic accuracy. However, current IVUS systems, with their unfocussed transducers, may not be capable of operating in harmonic imaging mode. Thus, there is a need to develop suitable transducers and appropriate techniques to allow imaging in multi modes for complementary diagnostic information.Focused PVDF TrFE transducers were developed using MEMS (Micro-Electro-Mechanical-Systems) compatible protocols. The transducers were characterized using pulse-echo techniques and exhibited broad bandwidth (110% at -6dB) with axial resolutions of <19 micron. These transducers were demonstrated to be suitable for harmonic imaging in IVUS. Improvements in lateral resolution for harmonic signals were investigated. A method was developed to present five modes of images (standard 40 MHz, fundamental 20 MHz (F20), fundamental 40 MHz (F40), harmonic 40 MHz (H40) and harmonic 80 MHz (H80)) using a single transducer.. Ex vivo human aorta and coronary ostium were imaged using PVDF TrFE transducers and compared to corresponding images from commercial systems. PVDF TrFE transducers demonstrated improved image quality and showed better definition of the calcific area in the coronary ostium when compared to the corresponding images from current IVUS systems. Standard mode40 MHz images of the human cadaveric aorta were obtained using PVDF TrFE transducers and compared to histology. The images demonstrated near histologic resolution and identified the loose connective tissue and focal necrotic area in the aorta. Such promising results suggest that focused, broadband PVDF TrFE transducers have opened up the potential to incorporate harmonic imaging modality in IVUS and also improve the image quality. In addition, the transducer's multimodality imaging capability, not possi (open full item for complete abstract)
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    Committee: Aaron J. Fleischman PhD (Committee Chair); Shuvo Roy PhD (Committee Member); George Chatzimavroudis PhD (Committee Member); Randolph Setser PhD (Committee Member); Miron Kaufman PhD (Committee Member) Subjects: Biomedical Research

  • 20. Wang, Ruolei Applications of Unconventional Processes in Polymer Synthesis – Supercritical Fluids and Sonochemistry

    Doctor of Philosophy, University of Akron, 2005, Engineering

    The polymer industry has become one of the fastest growing areas in the materials industry for several decades, and would be continue to do so in the foreseeable future. However, due to growing environmental and health concern, the polymer manufacturers have faced increasing pressure to apply environmentally benign technologies in order to accommodate tightened environmental regulations. In the process of searching for clean and low emission polymerization techniques, supercritical fluid technology and sonochemistry have attracted more and more interest because of their unique advantages over conventional techniques. The present study is to expand our knowledge of polymer synthesis processes involving supercritical fluid, sonochemistry and microemulsion technologies. This study included three affiliated projects as supercritical dispersion polymerization, ultrasonically initiated polymerization in near-critical environment and ultrasound assisted microemulsion polymerization in aqueous solution. The success of projects will significantly broaden the application potential for these advanced chemical processes in both conventional and unconventional systems. In the study of dispersion polymerization in scCO2, a new PDMS macromonomer has been successfully applied as surfactant to stabilize the polymerization process. The polymerization results indicated that the conversion is increasing with the increasing of stabilizer concentration, and the particle morphology become more uniform at the same time. In the study of ultrasound irradiation in high-pressure medium, it has been confirmed that sonication alone could initiate the polymerization process. The monomer: CO2 ratio and ultrasound irradiation time appeared to have impact on the molecular weight and its distribution of the polymeric products. Discrete morphology from SEM image suggested that the polymer particles could be stabilized without surfactant during the polymerization process. In the study of ultrasound ass (open full item for complete abstract)
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    Committee: Henry Cheung (Advisor) Subjects: Engineering, Chemical
Release 3.2.12