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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Neurovaskuläre Kopplung im somatosensorischen Kortex der Ratte

Royl, Georg Andreas 09 December 2002 (has links)
Die Grundlage der modernen funktionellen Bildgebung des Gehirns mit der BOLD-fMRT ist die neurovaskuläre Kopplung. Sie ist in ihren Mechanismen wenig verstanden und führt zu einem komplexen Zusammenspiel von Blutfluß, Blutvolumen und Oxygenierung. Die Aufklärung der Blutflußantwort mit ihren Auswirkungen auf die Meßsignale ist für eine genaue Interpretation des BOLD-Signals kritisch. Zudem stellt sich seit einigen Jahren die Frage, ob es bei funktioneller Aktivierung aufgrund eines vermehrten neuronalen Sauerstoffverbrauchs zu einer frühen Deoxygenierung kommt. Diese könnte sich als initialer BOLD-Abfall für eine hochauflösende Bildgebung eignen. Ein Vergleich von optischen Methoden und funktioneller Magnetresonanztomographie am gleichen Stimulationsmodell kann diesen Fragen nachgehen. Wir haben die kortikale Blutflußantwort auf somatosensorische Stimulation der Ratte mit den optischen Methoden Optical Imaging und Imaging Spectroscopy sowie mit BOLD-fMRT und blutvolumengewichteter MION-fMRT gemessen. Bei der Stimulation eines einzelnen Whisker-Haares grenzte sich die entsprechende kortikale Kolumne über eine optische Abschwächung ab. Spektroskopisch zeigte sich, daß diesem Signal eine initiale Blutvolumenzunahme zugrundeliegt. Eine Lambert-Beer-Analyse, die die differentiellen Pfadlängen des Lichtes im streuenden Gewebe vernachlässigt, konnte die gemessenen Spektren nicht linear anpassen. Mit einer Annäherung errechnete sie einen artifiziellen Anstieg des Deoxy-Hb in der frühen Antwort. Die quantifizierte Lambert-Beer-Analyse unter Einschluß der differentiellen Pfadlängen konnte die gemessenen Spektren linear anpassen. Im berechneten Konzentrationsverlauf stieg Oxy-Hb zum Stimulationsbeginn an, Deoxy-Hb blieb zunächst auf dem Ruhewert und fiel dann ab. Diese Verzögerung lag im Bereich der kapillären Transitzeit. Die spektroskopisch gemessene frühe Antwort fand sich auch in der Messung der Antwort auf Vorderpfotenstimulation. Zum Vergleich wurden fMRT-Messungen an diesem Stimulationsmodell herangezogen. Die MION-fMRT erfaßte einen initialen Anstieg des plasmatischen Blutvolumens (pCBV), das BOLD-Signal delta-R2* eine verzögerte Hyperoxygenierung. Die Hyperoxygenierung im weiteren Verlauf der Blutflußantwort zeigte in Imaging Spectroscopy und fMRT einen linearen Zusammenhang mit der Dauer der Stimulation. Dabei korrelierte die delta-R2* stark mit der spektroskopisch gemessenen Deoxy-Hb-Konzentration. Auch die Antwort auf das Stimulationsende stellte sich als von der Stimulationsdauer abhängig heraus und wurde als vaskuläres Speicherphänomen interpretiert. BOLD und Deoxy-Hb zeigten beide eine Hypooxygenierung nach dem Stimulationsende. pCBV und das spektroskopisch gemessene korpuskuläre Blutvolumen, cCBV, verhielten sich nach dem Stimulationsende spiegelbildlich. Die pCBV-Zunahme bildete sich nur allmählich zurück, während das cCBV steil unter seinen Ruhewert abfiel. Im Laufe der Messung nahm das cCBV wieder zu und erreichte seinen Ruhewert zeitgleich mit dem pCBV. Eine vermehrte Volumenspeicherung als Folge venöser Streßrelaxation und eine Verschiebung des Hämatokrits aufgrund des Fahraeus-Lindquist-Effekts werden als Grund für diese Veränderungen in Betracht gezogen. Die experimentellen Daten belegen, daß optische und magnetresonanztomographische Methoden korrespondierende Signale von Oxygenierung und Blutvolumen messen. Eine frühe Deoxygenierung wurde nicht gemessen. Allerdings zeigte sich die frühe Komponente der Blutvolumenzunahme an die initiale Kapillarnetzfüllung einer kortikalen Kolumne gebunden. Ihre Detektion mit der fMRT bietet eine Perspektive auf dem Weg zu einer hochauflösenden funktionellen Bildgebung des Gehirns. / Neurovascular coupling forms the basis of modern functional brain imaging with BOLD-fMRI. Its mechanisms are poorly understood as it leads to a complex interaction of blood flow, blood volume and oxygenation. The investigation of the blood flow response with its influences on measured signals is critical for the exact interpretation of the BOLD-Signal. In addition to that, the question on whether or not an increase in oxygen consumption during functional activation leads to an early deoxygenation is not resolved yet. This early deoxygenation could cause an initial BOLD decrease suitable for high resolution imaging. A comparison of optical methods and functional magnetic resonance imaging on the same stimulation model can help to answer these questions. We have measured the cortical blood flow response on somatosensory stimulation of the rat with the optical methods Optical Imaging and Imaging Spectroscopy and with BOLD-fMRI and blood volume weighted MION-fMRI. During stimulation of a single whisker vibrissa the corresponding cortical column delineated itself as an area of increased optical attenuation. A spectroscopical analysis showed an initial blood volume increase responsible for this signal. A Lambert-Beer-Analysis that ignored the differential pathlength of light in scattering tissue could not fit the measured spectra. The result of its closest approximation showed an artificial increase of deoxy-Hb during the early response. The quantified Lambert-Beer-Analysis with inclusion of differential pathlengths succeeded in fitting the measured spectra. The calculated concentration time course showed an increase of oxy-Hb at stimulus onset with deoxy-Hb staying at baseline values and then decreasing. This delay was as long as the capillary mean transit time. The spectroscopically measured early response was also found when measuring the response to forepaw stimulation. For comparison, fMRI measurements on this stimulation model were done. MION-fMRI detected an early increase of plasmatic blood volume (pCBV), the BOLD-Signal delta-R2* a delayed hyperoxygenation. The time course of the hyperoxygenation during the blood flow response showed a linear relationship with the stimulus duration in Imaging Spectroscopy and fMRI. The delta-R2* correlated strongly with spectroscopically measured concentration changes of deoxy-Hb. In addition to that, the response on the stimulus offset was dependent on the stimulus duration. It was interpreted as a vascular storage phenomenon. Both BOLD and deoxy-Hb showed a hypooxygenation after stimulus offset. pCBV and the spectroscopically measured corpuscular blood volume, cCBV, showed mirroring signals after stimulus offset. While pCBV returned to baseline values gradually, cCBV fell below baseline values immediately. During the further measurement cCBV increased and returned to baseline values at the same time as pCBV. To explain this, an increased volume storage due to venous stress relaxation and a hematocrit shift due to the Fahraeus-Lindquist effect are taken into consideration. The experimental data proves that optical and fMRI methods measure corresponding signals of oxygenation and blood volume. An early deoxygenation was not seen. However, the early component of the blood volume increase seems to be restricted to the initial filling of the capillary net supplying a cortical column. Its detection with fMRI offers a perspective on the way to high resolution functional imaging of the brain.
22

Order under the guise of chaos: functional neuroanatomy of the somatosensory "barrel" cortex of the reeler mutant mouse

Guy, Julien 01 December 2015 (has links)
No description available.
23

Thermoacoustic Imaging and Spectroscopy for Enhanced Cancer Diagnostics

Bauer, Daniel Ryan January 2012 (has links)
Early detection of cancer is paramount for improved patient survival. This dissertation presents work developing imaging techniques to improve cancer diagnostics and detection utilizing light and microwave induced thermoacoustic imaging. In the second chapter, the well-established pre-clinical mouse window chamber model is interfaced with simultaneously acquired high-resolution pulse echo (PE) ultrasound and photoacoustic (PA) imaging. Co-registered PE and PA imaging, coupled with developed image segmentation algorithms, are used to quantitatively track and monitor the size, shape, heterogeneity, and neovasculature of the tumor microenvironment during a month long study. Average volumetric growth was 5.35 mm³/day, which correlated well with two dimensional results from fluorescent imaging (R = 0.97, p < 0.01). Spectroscopic PA imaging is also employed to probe the assumed oxygenation status of the tumor vasculature. The window chamber model combined with high-resolution PE and PA imaging could form a powerful testbed for characterizing cancers and evaluating new contrast and therapeutic agents. The third chapter utilizes a clinical ultrasound array to facilitate fast volumetric spectroscopic PA imaging to detect and discriminate endogenous absorbers (i.e. oxy/deoxygenated hemoglobin) as well as exogenous PA contrast agents (i.e. gold nanorods, fluorophores). In vivo spatiotemporal tracking of administered gold nanorods is presented, with the contrast agent augmenting the PA signal 18 dB. Furthermore, through the use of spectral unmixing algorithms, the relative concentrations of multiple endogenous and exogenous co-localized absorbers were reconstructed in tumor bearing mice. The concentration of Alexaflour647 was calculated to increase nearly 20 dB in the center of a prostate tumor after a tail-vein injection of the contrast agent. Additionally, after direct subcutaneous injections of two different gold nanorods into a breast tumor, the concentration of each nanoparticle was discriminated in vivo with a signal-to-noise ratio of greater than 25 dB. This technique has great potential for improved early cancer detection and individualized cancer treatment through advanced pharmacokinetic monitoring of therapeutic agents. Finally, the fourth chapter presents significant improvements made to enhance breast cancer detection with thermoacoustic (TA) imaging. In a breast cancer simulating phantom, the initial demonstration of TA spectroscopy (TAS) is used to detect and discriminate relative water / fat composition based solely on the sample's intrinsic spectral absorption. The slope of the TA signal was highly correlated with that of the absorption coefficient (R² = 0.98, p < 0.01), indicating TAS can distinguish materials based on their dielectric properties. Furthermore, the use of carbon nanotubes as a potential TA contrast agent is explored. These nanoparticles significantly enhance the magnitude of the TA signal (8 dB larger than water), and also demonstrate unique absorption spectra. Finally, short microwave pulses (Δt ≥ 10 ns) are achieved through novel microwave hardware, and used to generate high-frequency TA signals. In conclusion, this section presents advancements made to the sensitivity, contrast, and resolution of TA imaging. Overall, this dissertation presents enhancements made to the diagnostic capabilities of PA and TA imaging for improved detection and characterization of cancer.
24

Bacterial protein complexes studied by single-molecule imaging and single-cell micromanipulation techniques in microfluidic devices

Reuter, Marcel January 2010 (has links)
Biological systems of bacteria were investigated at the single-cell and single-molecule level. Additionally, aspects of the techniques employed were studied. A unifying theme in each project is the reliance on optical imaging techniques coupled to microfluidic devices. Hypo-osmotic shock experiments with an Escherichia coli mechanosensitive channel deletion mutant were carried out at the single-cell level. E. coli MJF465 cells in which the three major mechanosensitive channel genes are deleted (∆mscL, ∆mscS, ∆mscK) show only 10% cell viability upon hypo-osmotic shock (from LB + 0.5 M NaCl into distilled water), compared to 90% viability of the wild-type strain. Bacterial cells were trapped with optical tweezers in microfluidic devices, enabling the first direct observation of single-cell behaviour upon hypo-osmotic shock. Phase-contrast microscopy revealed intra-population diversity in the cells response: Different features of lysis included cells bursting rapidly and leakage of ribosomes, DNA and protein from the cytoplasm. Fluorescence microscopy of hypo-osmotically-shocked GFP-expressing MJF465 cells showed either bursting of cells, which was a rare event, or fast leakage of GFP, indicating cell membrane ruptures. Data were analysed in terms of their kinetic behaviour and showed that lysis occurs on a timescale of milliseconds to seconds. The implications of these findings for the bacterial cell wall and cell membranes are discussed. Enzymes involved in homologous recombination and repair of double-stranded DNA (dsDNA) breaks are essential for maintaining genomic integrity in both eukaryotes and prokaryotes. RecBCD of E. coli and AddAB, found widely in bacteria, are involved in these processes, carrying out the same function. Both enzymes were studied kinetically with single-molecule total internal reflection fluorescence microscopy (TIRFM). Surface-tethered, hydrodynamically stretched lambda-DNA molecules, stained with YOYO-1, were imaged with TIRFM in a microfluidic flowcell. The RecBCD enzyme is a well characterised DNA helicase and was introduced to this system for method validation purposes. The AddAB enzyme of Bacteroides fragilis was then characterised as a helicase acting on lambda-DNA. It was found that AddAB helicase unwinds dsDNA with high processivity of on average 14,000 bp and up to 40,000 bp for individual enzyme complexes at an ATP-dependent rate ranging from 50-250 bp s−1 (for Mg2+-ATP concentrations larger or equal than 0.1 mM). This activity was detected by DNA binding dye (YOYO-1) displacement from the dsDNA and studied for different Mg2+-ATP concentrations, flow (shear) rates and different YOYO-1 staining ratios of DNA. Aspects of this last experimental setup were investigated. A kinetic analysis of intercalation of YOYO-1 into lambda-DNA is presented, occurring on a timescale of minutes. Different flow rates and staining ratios that influence the apparent (stretched) DNA molecule length were also examined. Several image analysis techniques were employed to enhance the data quality in images showing stretched lambda-DNA molecules. The Singular Value Decomposition was found to be the most effective technique which strongly reduces the noise in the obtained kymograph images.
25

Enhancing visual cortical plasticity in mice by enriching their environment: a combined imaging and behavioural study

Kalogeraki, Evgenia 15 February 2016 (has links)
No description available.
26

Development of an Autonomous Mammalian <i>lux</i> Reporter System

Close, Daniel Michael 01 May 2011 (has links)
Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of the bioluminescent signal, along with its characteristic lack of substrate amendment required for bioluminescent production, makes a mammalian-based lux reporter system ideal for real-time monitoring of cell culture or murine model systems. The delectability of a lux-based system provides for a functionally equivalent process to monitoring firefly luciferase-expressing cells under cell culture or subcutaneous imaging conditions without the well-documented uncertainties stemming from additional substrate introduction. However, the relatively blue-shifted emission wavelength of the lux reporter system, along with its low quantum yield, has been shown to reduce its effectiveness for use during deep tissue imaging of animal subjects. Despite these disadvantages, it has been demonstrated that a human cell line expressing the human codon-optimized lux genes can function as a biosensor for determination of human bioavailability of toxic compounds and that, by regulating the production of the luxC and luxE genes, the lux system can be employed as the first mammalian, real-time, fully autonomous bioreporter. These cell lines provide unique and efficient models for the detection and monitoring of human-relevant compounds of interest. The limiting reagent for bioluminescent production in the mammalian cellular background has been determined to be the cytosolic availability of the FMNH2 co-substrate and, in light of this evidence, directions for future optimization have been characterized and evaluated in respect to their ability to increase bioluminescent yield under these conditions.
27

Computational Optical Imaging Systems for Spectroscopy and Wide Field-of-View Gigapixel Photography

Kittle, David S. January 2013 (has links)
<p>This dissertation explores computational optical imaging methods to circumvent the physical limitations of classical sensing. An ideal imaging system would maximize resolution in time, spectral bandwidth, three-dimensional object space, and polarization. Practically, increasing any one parameter will correspondingly decrease the others.</p><p>Spectrometers strive to measure the power spectral density of the object scene. Traditional pushbroom spectral imagers acquire high resolution spectral and spatial resolution at the expense of acquisition time. Multiplexed spectral imagers acquire spectral and spatial information at each instant of time. Using a coded aperture and dispersive element, the coded aperture snapshot spectral imagers (CASSI) here described leverage correlations between voxels in the spatial-spectral data cube to compressively sample the power spectral density with minimal loss in spatial-spectral resolution while maintaining high temporal resolution.</p><p>Photography is limited by similar physical constraints. Low f/# systems are required for high spatial resolution to circumvent diffraction limits and allow for more photon transfer to the film plain, but require larger optical volumes and more optical elements. Wide field systems similarly suffer from increasing complexity and optical volume. Incorporating a multi-scale optical system, the f/#, resolving power, optical volume and wide field of view become much less coupled. This system uses a single objective lens that images onto a curved spherical focal plane which is relayed by small micro-optics to discrete focal planes. Using this design methodology allows for gigapixel designs at low f/# that are only a few pounds and smaller than a one-foot hemisphere.</p><p>Computational imaging systems add the necessary step of forward modeling and calibration. Since the mapping from object space to image space is no longer directly readable, post-processing is required to display the required data. The CASSI system uses an undersampled measurement matrix that requires inversion while the multi-scale camera requires image stitching and compositing methods for billions of pixels in the image. Calibration methods and a testbed are demonstrated that were developed specifically for these computational imaging systems.</p> / Dissertation
28

HelioScan : A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility

Langer, Dominik, van 't Hoff, Marcel, Keller, Andreas J., Nagaraja, Chetan, Pfaeffli, Oliver A., Goeldi, Maurice, Kasper, Hansjoerg, Helmchen, Fritjof January 2013 (has links)
Intravital microscopy such as in vivo imaging of brain dynamics is often performed with custom-built microscope setups controlled by custom-written software to meet specific requirements. Continuous technological advancement in the field has created a need for new control software that is flexible enough to support the biological researcher with innovative imaging techniques and provide the developer with a solid platform for quickly and easily implementing new extensions. Here, we introduce HelioScan, a software package written in LabVIEW, as a platform serving this dual role. HelioScan is designed as a collection of components that can be flexibly assembled into microscope control software tailored to the particular hardware and functionality requirements. Moreover, HelioScan provides a software framework, within which new functionality can be implemented in a quick and structured manner. A specific HelioScan application assembles at run-time from individual software components, based on user-definable configuration files. Due to its component-based architecture, HelioScan can exploit synergies of multiple developers working in parallel on different components in a community effort. We exemplify the capabilities and versatility of HelioScan by demonstrating several in vivo brain imaging modes, including camera-based intrinsic optical signal imaging for functional mapping of cortical areas, standard two-photon laser-scanning microscopy using galvanometric mirrors, and high-speed in vivo two-photon calcium imaging using either acousto-optic deflectors or a resonant scanner. We recommend HelioScan as a convenient software framework for the in vivo imaging community. / <p>Paid Open Access</p>
29

Multimodal Optical Imaging for Detection of Cervical Neoplasia

Bubi, Tefo 16 September 2013 (has links)
Despite being the most preventable cancer, cervical cancer remains the third leading cause of cancer death worldwide. Over 85% of cervical cancer incidence and mortality occurs in low-resource countries where screening programs for early detection are either inadequate or unavailable. In the developed world, where screening programs are well organized, incidence and mortality rates are greatly reduced. Recent advances in optical imaging have the potential to enable cervical cancer screening at the point-of-care, even in the hands of less experienced providers. High performance optical imaging systems can be constructed at relatively low cost, and image analysis can be automated; thus, these technologies may provide a way to bridge the gap to cervical cancer screening for developing countries. This work focuses on the design, construction, and clinical testing of a novel multimodal optical imaging (combination of wide-field imaging and high-resolution) for early detection of cervical neoplasia. The Multimodal Digital Imager (MDI) acquires in vivo images of cervical tissue in fluorescence, narrow band reflectance, and orthogonal polarized reflectance modes using multiple illumination wavelengths. The High Resolution Microendoscope (HRME) was used to interrogate clinically suspicious areas with subcellular spatial resolution, revealing changes in nuclear to cytoplasmic area ratio. In vivo image data from the wide-field system was combined with image data from a high- resolution microendoscope (HRME) in order to test the effectiveness of the multimodal optical imaging in discriminating between cervical neoplasia and non-neoplastic. Multimodal optical imaging coupled with computer aided diagnostic achieved a sensitivity of 82% and specificity of 85% for discriminating cervical neoplastic from non-neoplastic This work has demonstrated that multimodal optical imaging; combination of wide-field and high-resolution optical imaging of the cervix can assist in the detection of cervical neoplasia and can be implemented effectively in a low-resource setting.
30

Optical Contrast Agents to Visualize Molecular Expression in Breast Cancer

Langsner, Robert 16 September 2013 (has links)
Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxy-glucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous tissue, a portable, inexpensive device was developed as a tool to help physicians visualize expression of surface markers. The system visualizes absorbance from nanoshell aggregates and fluorescence in the visible and near-infrared light spectrum. This study represents the first step in the development of an intraoperative optical imaging device to enhance the visualization of molecular markers overexpressed in cancerous cells.

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