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Ultrasound-Encoded Optical Tomography And Time-Reversed Ultrasonically Encoded Optical Focusing, Xiao Xu
Ultrasound-Encoded Optical Tomography And Time-Reversed Ultrasonically Encoded Optical Focusing, Xiao Xu
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Ultrasound modulated optical tomography is a developing hybrid imaging modality that combines high optical contrast and good ultrasonic resolution to image soft biological tissue. We developed a photorefractive crystal-based, time-resolved detection scheme with the use of a millisecond long ultrasound burst to image both the optical and mechanical properties of biological tissues, with improved detection efficiency of ultrasound-tagged photons. We also applied spectral-hole burning: SHB) aided detection in ultrasound-modulated optical tomography: UOT) to image optical heterogeneities in thick tissue-mimicking phantom samples and chicken breast tissue. The efficiency of SHB was improved by using a Tm3+: YAG crystal of higher doping …
Simulation Of The Undiseased Human Cardiac Ventricular Action Potential: Model Formulation, Experimental Validation And Application, Thomas O'Hara
Simulation Of The Undiseased Human Cardiac Ventricular Action Potential: Model Formulation, Experimental Validation And Application, Thomas O'Hara
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Creation of an accurate model for the undiseased human ventricular action potential: AP) which reproduces a broad range of physiological behaviors requires extensive experimental data, of which essential elements have been unavailable. We developed and validated such a model using new experimental data from endocardium of 140 undiseased human hearts. 78 were from male: 56%). Average age was 41 with standard deviation of 12 years. New experiments include: Ca2+ versus voltage dependent inactivation of L-type Ca2+ current; kinetics for the transient outward, rapid delayed rectifier, Na+/Ca2+ exchange, and inward rectifier currents; AP recordings at all …
The Interaction Of Cofilin With The Actin Filament, Diana Wong
The Interaction Of Cofilin With The Actin Filament, Diana Wong
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The regulation of filamentous actin: F-actin) production from the polymerization of globular actin: G-actin) within the cell is critical for many cell functions. Since actin is found in all cells, understanding how actin-binding-proteins: ABPs) bind and how their regulating mechanisms work is not only important to the basics of cytoskeletal pathways, but also to understanding associated diseases and creating possible therapeutics to combat them. Cofilin is an ABP that plays an important part in the regulation process and in recent times, has come to be known as a player in maintaining a cell's homeostasis. It's activity has been shown to …
Inferring Aggregation Mechanisms Of Molecules Involved In Neurodegeneration Through Quantitative Studies Of Phase Behavior, Scott Crick
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Polyglutamine is involved in at least nine known neurodegenerative diseases, the most prominent of which is Huntington's Disease. It is thought that polyglutamine aggregation leads to disease. The biophysical mechanism of polyglutamine aggregation remains controversial as highlighted by conflicting proposals that have been put forth in the literature ranging from homogeneous nucleation to a more complex assembly mechanism that involves heterogeneous distributions of oligomers. Converging upon an accurate framework for describing polyglutamine aggregation in vitro is an essential first step for understanding how interactions in cis i.e., flanking sequences and trans i.e., heterotypic interactions in the cellular milieu shape self-assembly …
Advances In Real-Time Thoracic Guidance Systems, Ryan Smith
Advances In Real-Time Thoracic Guidance Systems, Ryan Smith
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Substantial tissue motion: >1cm) arises in the thoracic/abdominal cavity due to respiration. There are many clinical applications in which localizing tissue with high accuracy: <1mm) is important. Potential applications include radiation therapy, radio frequency ablation, lung/liver biopsies, and brachytherapy seed placement. Recent efforts have made highly accurate sub-mm 3D localization of discrete points available via electromagnetic: EM) position monitoring. Technology from Calypso Medical allows for simultaneous tracking of up to three implanted wireless transponders. Additionally, Medtronic Navigation uses wired electromagnetic tracking to guide surgical tools for image guided surgery: IGS). Utilizing real-time EM position monitoring, a prototype system was developed to guide a therapeutic linear accelerator to follow a moving target: tumor) within the lung/abdomen. In a clinical setting, electromagnetic transponders would be bronchoscopically implanted into the lung of the patient in or near the tumor. These transponders would ax to the lung tissue in a stable manner and allow real-time position knowledge throughout a course of radiation therapy. During each dose of radiation, the beam is either halted when the target is outside of a given threshold, or in a later study the beam follows the target in real-time based on the EM position monitoring. We present quantitative analysis of the accuracy and efficiency of the radiation therapy tumor tracking system. EM tracking shows promise for IGS applications. Tracking the position of the instrument tip allows for minimally invasive intervention and alleviates the trauma associated with conventional surgery. Current clinical IGS implementations are limited to static targets: e.g. craniospinal, neurological, and orthopedic intervention. We present work on the development of a respiratory correlated image guided surgery: RCIGS) system. In the RCIGS system, target positions are modeled via respiratory correlated imaging: 4DCT) coupled with a breathing surrogate representative of the patient's respiratory phase/amplitude. Once the target position is known with respect to the surrogate, intervention can be performed when the target is in the correct location. The RCIGS system consists of imaging techniques and custom developed software to give visual and auditory feedback to the surgeon indicating both the proper location and time for intervention. Presented here are the details of the IGS lung system along with quantitative results of the system accuracy in motion phantom, ex-vivo porcine lung, and human cadaver environments.
Nonuniform Power Changes And Spatial, Temporal And Spectral Diversity In High Gamma Band (>60 Hz) Signals In Human Electrocorticography, Charles Gaona
Nonuniform Power Changes And Spatial, Temporal And Spectral Diversity In High Gamma Band (>60 Hz) Signals In Human Electrocorticography, Charles Gaona
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High-gamma band: >60Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. In spite of discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60Hz. Based on non-uniformities in time-frequency analyses of electrocorticographic: ECoG) signals, we hypothesized …
Spray Techniques And Lung Cancer Chemoprevention, Huijing Fu
Spray Techniques And Lung Cancer Chemoprevention, Huijing Fu
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Chemoprevention is a promising approach to decrease the incidence of lung cancer in current and former smokers. Directly delivering drugs to the lung could lead to a high concentration in the target organ with a lower dose compared to other means of administration. The primary advantages of aerosol delivery in treating lung diseases include improving the bioavailability of the drug in the lung, decreasing the medicine dose, rapid action, and reducing the systemic toxicity as well as side effects. Spray techniques are widely used for aerosol delivery. Two spray techniques were evaluated in this study for their applications in lung …
Cellular And Cytoskeletal Responses Of Myofibroblasts In Three Dimensional Culture To Mechanical Stretch, Sheng-Lin Lee
Cellular And Cytoskeletal Responses Of Myofibroblasts In Three Dimensional Culture To Mechanical Stretch, Sheng-Lin Lee
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Myofibroblasts play important roles in wound healing and pathological organ remodeling, such as hypertensive cardiac fibrosis and promotion of metastasis. Differentiated myofibroblasts are characterized by increased production of extracellular matrix: ECM) proteins and by the development of α-smooth muscle actin: α-SMA) positive stress fibers that are connected to the ECM through focal adhesion assemblies. Moreover, mounting evidence suggests that development of myofibroblasts is profoundly influenced by the mechanical microenvironment, especially, by the structure, organization or stiffness of the ECM: Hinz and Gabbiani, 2003a). Myofibroblasts are likely signaled by mechanical changes in their environment transduced through their cytoskeletons, and the fundamental …
Engineering Noble-Metal Nanoparticles For Sensing And Imaging With Surface-Enhanced Raman Scattering, Matthew Rycenga
Engineering Noble-Metal Nanoparticles For Sensing And Imaging With Surface-Enhanced Raman Scattering, Matthew Rycenga
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This research investigated the surface-enhanced Raman scattering: SERS) from Ag and Au nanoparticles with an aim to better understand the SERS mechanism and to implement this technique for single-molecule detection and imaging. In addition, SERS was used as a sensitive probe to study molecules confined to a nanoparticle's surface. The first part of this work focused on measuring the SERS from different Ag and Au nanoparticles and determining how their structural and physical properties affect SERS. The effects of shape, size, and Au-Ag composition on SERS are determined using Ag nanocubes, Ag nanospheres, and Au-based nanocages. I also demonstrate several …
Quantitative Perfusion-Sensitive Mri Phantoms, Jeff Anderson
Quantitative Perfusion-Sensitive Mri Phantoms, Jeff Anderson
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Perfusion-sensitive MR methods are increasingly utilized in preclinical and clinical MR research studies with the promise of providing quantitative estimates of parameters that describe in vivo microvasculature. One of these techniques, dynamic contrast enhanced: DCE) MRI, has found particularly common use in oncology for the detection, staging, and monitoring of highly vascularized tumors. DCE-MRI has been qualitatively validated by various studies that show a high correlation between modeled parameters from DCE and histologically measured microvascular density: MVD). However, in the absence of a matching "gold-standard" technique, DCE-MRI has not yet been quantitatively validated: i.e., the accuracy of the estimated parameters …
Atrial Arrhythmogenic Substrates: The Role Of Structure And Molecular Remodeling, Christina Ambrosi
Atrial Arrhythmogenic Substrates: The Role Of Structure And Molecular Remodeling, Christina Ambrosi
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Atrial tachyarrhythmias, specifically atrial flutter: AFl) and fibrillation: AF), affect over 2.2 million Americans, leading to more hospitalizations than any other cardiac arrhythmia. These arrhythmias are defined by the presence of reentrant circuits of excitation leading to high atrial rates and uncoordinated activation of the ventricles. The underlying mechanisms of AFl/AF have proven complex and, despite a century of research, no one effective treatment has been developed. Surgical ablation and pharmacological therapies are both fraught with risks and potential pro-arrhythmic side effects. Electrical cardioversion, on the other hand, is extremely effective in terminating these arrhythmias, but the high-energy shocks required …
New Paradigm Of Defibrillation: Towards Painless Therapy, Wenwen Li
New Paradigm Of Defibrillation: Towards Painless Therapy, Wenwen Li
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Sudden cardiac death: SCD) causes approximately 300,000 - 400,000 deaths a year in the United States. It usually starts as ventricular tachycardia: VT) and then degenerates into ventricular fibrillation: VF). Implantable cardioverter defibrillator: ICD) therapy is the only reliable treatment of VT/VF and has been shown to effectively reduce mortality by many clinical trials. However, high-voltage ICD shocks could result in myocardial dysfunction and damage. The majority of patients receiving ICD therapy have a history of coronary disease; their hearts develop myocardium infarction, which could provide a substrate for reentrant tachy-arrhythmias. Other than lethal ventricular tachycardia, atrial fibrillation: AF) became …
Cardiac Remodeling Of Conduction, Repolarization And Excitation-Contraction Coupling: From Animal Model To Failing Human Heart, Qing Lou
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Heart failure is one of the leading causes of death worldwide, with rising impact with the increasing ageing population. This is in sharp contrast with the limited and non-ideal therapies available. Approximately 50% of deaths from heart failure are sudden and unexpected, and presumably the consequence of lethal ventricular arrhythmias. Despite significant reduction of mortality from sudden cardiac death achieved by ICDs and drugs such as beta-blockers, there remains a large room for improving the survivability of heart failure patients by advancing our understanding of arrhythmogenesis from molecular level to multi-cellular tissue level. Another important aspect of heart failure is …
Pathological And Biomedical Characteristics Of Spinal Cord Injury Determined Using Diffusion Tensor Imaging, Tsang-Wei Tu
Pathological And Biomedical Characteristics Of Spinal Cord Injury Determined Using Diffusion Tensor Imaging, Tsang-Wei Tu
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Traumatic spinal cord injury: SCI) is the most devastating injury that often causes the victim permanent paralysis and undergo a lifetime of therapy and care. It is caused by a mechanical impact that ultimately causes pathophysiological consequences which at this moment in time are an unresolved scientific challenge of great social impact. Scientists have long used animal contusion models to study the pathophysiology of SCI in the discovery of progressive secondary tissue degeneration, demyelination, and apoptosis. More importantly, most therapies that have gone to human clinical trial were first validated in spinal cord contusion models. Magnetic resonance imaging: MRI) is …
Photoacoustic Reporter Gene Imaging And Optical Coherence Computed Tomography, Li Li
Photoacoustic Reporter Gene Imaging And Optical Coherence Computed Tomography, Li Li
All Theses and Dissertations (ETDs)
Advances in imaging technologies have always been the major driving forces for the evolution of biomedical research. Compared with other modalities, optical imaging possesses several prominent merits. Because light interacts with tissue at the microscopic level through many distinct physical mechanisms, optical methods allow sensitive exploration of various aspects of the life down to the single-molecule level. From the technical perspective, optical systems utilize safe non-ionizing radiation, could be implemented at relatively low cost, also have the potential to be miniaturized for portable or endoscopic applications. As a result, optical imaging tools are playing an increasingly important role in both …
Optical-Resolution Photoacoustic Microscopy, Song Hu
Optical-Resolution Photoacoustic Microscopy, Song Hu
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Optical microscopy, providing valuable biomedical insights at the cellular and organelle levels, has been widely recognized as an enabling technology. Mainstream optical microscopy technologies, including single-/multi-photon fluorescence microscopy and OCT, have demonstrated extraordinary sensitivities to fluorescence and optical scattering contrasts, respectively. However, the optical absorption contrast of biological tissues, which encodes essential physiological/pathological information, has not yet been fully assessable. The emergence of biomedical photoacoustics has led to a new branch of optical microscopy--OR-PAM. As a valuable complement to existing optical microscopy technologies, OR-PAM detects optical absorption contrasts with exquisite sensitivity: i.e., 100%). Combining OR-PAM with fluorescence microscopy or optical-scattering-based …
Structural And Functional Studies On Bk(Ca) Channels, Akansha Saxena
Structural And Functional Studies On Bk(Ca) Channels, Akansha Saxena
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The long term goal of this research is to study the structure and function of the BKCa channels, by focusing on the effect of a single residue mutation, the epilepsy mutation. BKCa channels are potassium channels, activated by voltage, Ca2+ and Mg2+ ions. These factors control the opening and closing of the channel pore and thus regulate the large K+ current passing through them. Recently, a mutation D434G in humans, was found to make the channel hyperactive and more sensitive to the Ca2+ ions. The single residue mutation, resulting from a substitution of an Asp to Gly, was …
High-Speed Photoacoustic Microscopy In Vivo, Liang Song
High-Speed Photoacoustic Microscopy In Vivo, Liang Song
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The overarching goal of this research is to develop a novel photoacoustic microscopy: PAM) technology capable of high-speed, high-resolution 3D imaging in vivo. PAM combines the advantages of optical absorption contrast and ultrasonic resolution for deep imaging beyond the quasi-ballistic regime. Its high sensitivity to optical absorption enables the imaging of important physiological parameters, such as hemoglobin concentration and oxygen saturation, which closely correlate with angiogenesis and hypermetabolism--two hallmarks of cancer. To translate PAM to the clinic, both high imaging speed and high spatial resolution are desired. With high spatial resolution, PAM can detect small structural and functional changes early; …
Synthesis Of Complex Plasmonic Nanostructures For Applications In Surface-Enhanced Raman Spectroscopy And Biomedicine, Claire Cobley
Synthesis Of Complex Plasmonic Nanostructures For Applications In Surface-Enhanced Raman Spectroscopy And Biomedicine, Claire Cobley
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This research centers around techniques to engineer the properties of noble-metal nanostructures for applications in surface-enhanced Raman spectroscopy: SERS) and biomedicine. Many of these potential applications are made possible by the strong localized surface plasmon resonance: LSPR) of noble-metal nanostructures, which is heavily influenced by the particle's morphology. The first part of this work focuses on the solution-phase synthesis of Ag nanostructures. In this section, I demonstrate the synthesis of Ag nanostructures with two different morphologies that are interesting for fundamental SERS studies: anisotropically truncated octahedrons and large, single-crystalline spheres. In both syntheses, control over etching was critical to morphological …