50 research outputs found

    Endoscopic Optical Coherence Tomography: Design and Application

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    This thesis presents an investigation on endoscopic optical coherence tomography (OCT). As a noninvasive imaging modality, OCT emerges as an increasingly important diagnostic tool for many clinical applications. Despite of many of its merits, such as high resolution and depth resolvability, a major limitation is the relatively shallow penetration depth in tissue (about 2∼3 mm). This is mainly due to tissue scattering and absorption. To overcome this limitation, people have been developing many different endoscopic OCT systems. By utilizing a minimally invasive endoscope, the OCT probing beam can be brought to the close vicinity of the tissue of interest and bypass the scattering of intervening tissues so that it can collect the reflected light signal from desired depth and provide a clear image representing the physiological structure of the region, which can not be disclosed by traditional OCT. In this thesis, three endoscope designs have been studied. While they rely on vastly different principles, they all converge to solve this long-standing problem. A hand-held endoscope with manual scanning is first explored. When a user is holding a hand- held endoscope to examine samples, the movement of the device provides a natural scanning. We proposed and implemented an optical tracking system to estimate and record the trajectory of the device. By registering the OCT axial scan with the spatial information obtained from the tracking system, one can use this system to simply ‘paint’ a desired volume and get any arbitrary scanning pattern by manually waving the endoscope over the region of interest. The accuracy of the tracking system was measured to be about 10 microns, which is comparable to the lateral resolution of most OCT system. Targeted phantom sample and biological samples were manually scanned and the reconstructed images verified the method. Next, we investigated a mechanical way to steer the beam in an OCT endoscope, which is termed as Paired-angle-rotation scanning (PARS). This concept was proposed by my colleague and we further developed this technology by enhancing the longevity of the device, reducing the diameter of the probe, and shrinking down the form factor of the hand-piece. Several families of probes have been designed and fabricated with various optical performances. They have been applied to different applications, including the collector channel examination for glaucoma stent implantation, and vitreous remnant detection during live animal vitrectomy. Lastly a novel non-moving scanning method has been devised. This approach is based on the EO effect of a KTN crystal. With Ohmic contact of the electrodes, the KTN crystal can exhibit a special mode of EO effect, termed as space-charge-controlled electro-optic effect, where the carrier electron will be injected into the material via the Ohmic contact. By applying a high voltage across the material, a linear phase profile can be built under this mode, which in turn deflects the light beam passing through. We constructed a relay telescope to adapt the KTN deflector into a bench top OCT scanning system. One of major technical challenges for this system is the strong chromatic dispersion of KTN crystal within the wavelength band of OCT system. We investigated its impact on the acquired OCT images and proposed a new approach to estimate and compensate the actual dispersion. Comparing with traditional methods, the new method is more computational efficient and accurate. Some biological samples were scanned by this KTN based system. The acquired images justified the feasibility of the usage of this system into a endoscopy setting. My research above all aims to provide solutions to implement an OCT endoscope. As technology evolves from manual, to mechanical, and to electrical approaches, different solutions are presented. Since all have their own advantages and disadvantages, one has to determine the actual requirements and select the best fit for a specific application.</p

    Development of polarization-resolved optical scanning microscopy imaging techniques to study biomolecular organizations

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    Light, as electromagnetic radiation, conveys energy through space and time via fluctuations in electric and magnetic fields. This thesis explores the interaction of light and biological structures through polarization-resolved imaging techniques. Light microscopy, and polarization analysis enable the examination of biological entities. Biological function often centers on chromatin, the genetic material composed of DNA wrapped around histone proteins within cell nuclei. This structure's chiral nature gives rise to interactions with polarized light. This research encompasses three main aspects. Firstly, an existing multimodal Circular Intensity Differential Scattering (CIDS) and fluorescence microscopy are upgraded into an open configuration to be integrated with other modalities. Secondly, a novel cell classification method employing CIDS and a phasor representation is introduced. Thirdly, polarization analysis of fluorescence emission is employed for pathological investigations. Accordingly, the thesis is organized into three chapters. Chapter 1 lays the theoretical foundation for light propagation and polarization, outlining the Jones and Stokes-Mueller formalisms. The interaction between light and optical elements, transmission, and reflection processes are discussed. Polarized light's ability to reveal image contrast in polarizing microscopes, linear and nonlinear polarization-resolved microscopy, and Mueller matrix microscopy as a comprehensive technique for studying biological structures are detailed. Chapter 2 focuses on CIDS, a label-free light scattering method, including a single point angular spectroscopy mode and scanning microscopy imaging. A significant upgrade of the setup is achieved, incorporating automation, calibration, and statistical analysis routines. An intuitive phasor approach is proposed, enabling image segmentation, cell discrimination, and enhanced interpretation of polarimetric contrast. As a result, image processing programs have been developed to provide automated measurements using polarization-resolved laser scanning microscopy imaging integrated with confocal fluorescence microscopy of cells and chromatin inside cell nuclei, including the use of new types of samples such as progeria cells. Chapter 3 applies a polarization-resolved two-photon excitation fluorescence (2PEF) microscopy to study multicellular cancerous cells. A homemade 2PEF microscope is developed for colon cancer cell analysis. The integration of polarization and fluorescence techniques leads to a comprehensive understanding of the molecular orientation within samples, particularly useful for cancer diagnosis. Overall, this thesis presents an exploration of polarization-resolved imaging techniques for studying biological structures, encompassing theory, experimental enhancements, innovative methodologies, and practical applications

    Specific diagnostics needs for different machines

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    Beam Diagnostic Requirements: an Overview

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    Beam diagnostics and instrumentation are an essential part of any kind of accelerator. There is a large variety of parameters to be measured for observation of particle beams with the precision required to tune, operate, and improve the machine. In the first part, the basic mechanisms of information transfer from the beam particles to the detector are described in order to derive suitable performance characteristics for the beam properties. However, depending on the type of accelerator, for the same parameter, the working principle of a monitor may strongly differ, and related to it also the requirements for accuracy. Therefore, in the second part, selected types of accelerators are described in order to illustrate specific diagnostics needs which must be taken into account before designing a related instrument.Comment: 102 pages, contribution to the CAS - CERN Accelerator School: Beam Instrumentation, 2-15 June 2018, Tuusula, Finlan

    Simulation and measurement of the dynamics of ultra-short electron bunch profiles for the generation of coherent THz radiation

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    The shape of an electron bunch has a tremendous impact on its emission of synchrotron radiation. Especially the formation of sub-structures can increase the yield in the THz region. This thesis investigates the micro-bunching instability, a mechanism where structures form due to self-interaction of the electrons with their own wake-field. The methods include simulation and measurements. On the simulation side, the thesis describes the optimization of simulation algorithms to increase numerical stability as well as computational performance. On the experimental side, an optimized monitor for single-shot bunch profile measurements was designed to allow continuous bunch profile measurements with high signal-to-noise ratio and a sub-ps resolution at 2.7 MHz repetition rate

    POSITRONIUM LASER EXCITATION IN THE AEGIS EXPERIMENT

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    The AEgIS experimental program on antimatter systems involves the formation of antihydrogen atoms for gravitational and CPT studies. One of the key ingredients of the AEgIS strategy for the synthesis of antihydrogen atoms is the creation and manipulation of Positronium (Ps) atoms laser excited to Rydberg states (n > 15). In AEgIS, Ps is produced in bunched mode and the Rydberg excitation is achieved with a two laser pulse technique, by passing through a n = 3 intermediate level. Because excitation on Ps n = 3 state has never been proposed before, in AEgIS a dedicated experimental apparatus and several detection strategies have been studied in order to observe the first measurement ever on this interesting process. In this work we present and discuss the experimental findings about the successful Ps n = 3 excitation. Moreover, in this thesis, a study of the impact of involved nonlinear processes on the excitation efficiency of a Doppler broadened atomic cloud is carried out. Presented simulation results show that, by exploiting properly nonlinear processes in the generation of the desired wavelength, it is possible to improve the excitation efficiency of a laser pulse. It is crucial, in AEgIS, the use of a periodically poled crystal in quasi phase matching regime. This gives a broadband continuous output spectrum whose wings survive to the spectral cutting of the last nonlinear crystal of the chain (which has insufficient spectral acceptance). This means that, at high laser energies, these wings can be amplified and the spectrum gaps can be filled in, leading to high reachable saturation efficiencies. On the contrary, in a laser pulse with a comb-shaped spectrum with a Gaussian envelope, both wings and gaps drop rapidly to zero, and amplification hardly occurs at usually employed energy regimes. The presented model is finally used to fit AEgIS Ps n = 3 excitation experimental data

    Stable, ultra-relativistic electron beams by laser-wakefield acceleration

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    IRIDE: Interdisciplinary Research Infrastructure Based on Dual Electron Linacs and Lasers

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    Laser-driven proton acceleration and detection at high repetition rate

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    [ES]Durante más de dos décadas, la aceleración de protones impulsada por láser ha sido un campo importante de investigación con un interés potencial para varias aplicaciones en diferentes campos de la física, la química y la ciencia de los materiales, así como en el área biomédica y el patrimonio cultural. Sin embargo, la interacción láser-materia es un proceso complejo que todavía no está totalmente controlado y la interacción resultante depende principalmente de los parámetros del láser y del plasma. Se están desarrollando diversas actuaciones para comprender el proceso detrás de este mecanismo a través de la caracterización de las propiedades espectrales y espaciales del haz de protones. Con la llegada de los láseres de alta potencia que funcionan con alta repetición, por lo tanto, es esencial un desarrollo cuidadoso de diagnósticos de partículas adecuados para el análisis en tiempo real de disparo a disparo. La tesis doctoral se centra en la generación, transporte y detección de una fuente de protones generada por láser. En la primera parte de la tesis se explorará la teoría de los protones y los electrones rápidos generados por la interacción de un pulso láser ultra intenso en un plasma sobredenso. En la segunda parte, se presenta el desarrollo de un detector de protones basado en centelleo, capaz de medir tanto la energía del haz de protones como su distribución espacial y capaz de operar en un modo de alta repetición. El detector ha sido diseñado y construido en el Centro de Láseres Pulsados (CLPU) y probado en colaboración con instalaciones europeas. El trabajo relacionado con el desarrollo de este nuevo diagnóstico, incluidas las investigaciones tanto teóricas como experimentales, se describe en la tesis. La parte final de la tesis está dedicada a los experimentos de puesta en marcha del sistema láser de petavatio VEGA-3. Se presentan la implementación de nuestro detector de centelleo y los resultados preliminares del experimento.[EN]For more than two decades, laser-driven proton acceleration has been an important eld of research with a potential interest for several applications in di erent elds of physics, chemistry and material science as well as biomedical and cultural heritage. However, the laser-matter interaction is a complex process which is still not totally controlled and the resulting interaction depends mainly on laser and plasma parameters. Still many studies are carried out to understand the process behind this mechanism through the characterization of the spectral and spatial properties of the proton beam. With the advent of high power lasers working at high repetition rate, a careful development of particle diagnostics suitable for online shot-to shot analysis is therefore essential. The PhD thesis focuses on the generation, transport and detection of laser-driven proton source. The theory of protons and fast electrons driven by the interaction of ultra-intense laser pulse in overdense plasma will be explored in the rst part of the thesis. In a second part, the development of a scintillator-based proton detector, able to measure both the proton beam energy and its spatial distribution and capable of being set in a high repetition mode is presented. The detector has been designed and built at the Spanish Center for Pulsed Lasers (CLPU) and tested in collaboration with facilities across the EU. The work related to the development of this new diagnostic, including both theoretical and experimental investigations, is described in the thesis. The nal part of the thesis is dedicated to the commissioning experiments of the petawatt laser system VEGA 3, which has recently started the operation phase. Implementation of our scintillator detector and preliminary results of the experiment are presente

    Tumor vasculature and microenvironment during progression and treatment : insights from optical microscopy

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    Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, February 2010.Vita. Cataloged from PDF version of thesis.Includes bibliographical references.In addition to cancer cells, solid tumors consist of a variety of cell types and tissues defining a complex microenvironment that influences disease progression and response to therapy. To fully characterize and probe the tumor microenvironment, new tools are needed to quantitatively assess microanatomical and physiological changes during tumor growth and treatment. Particularly important, is the metabolic microenvironment defined in tumors by hypoxia (low p02) and acidity (low pH). These parameters have been shown to influence response to radiation therapy and chemotherapy. However, very little is known about spatio-temporal changes in p02 and pH during tumor progression and therapy. By modifying the technique of intravital multiphoton microscopy (MPM) to perform phosphorescence quenching microscopy, I developed a non-invasive method to quantify oxygen tension (p02) in living tissue at high three-dimensional resolution. To probe functional changes in the metabolic microenvironment, I measured in vivo P02 during tumor growth and antiangiogenic (vascular targeted) treatment in preclinical tumor models. Nanotechnology is rapidly emerging as an important source of biocompatible tools that may shape the future of medical practice. Fluorescent semiconductor nanocrystals (NCs), also known as quantum dots, are a powerful tool for biological imaging, cellular targeting and molecular sensing.(cont.) I adapted novel fluorescence resonance energy transfer (FRET) -based nanocrystal (NC) biosensors for use with MPM to qualitatively measure in vivo extracellular pH in tumors at high-resolution. While intravital multiphoton microscopy demonstrates utility and adaptability in the study of cancer and response to therapy, the requisite high numerical aperture and exogenous contrast agents result in a limited capacity to investigate substantial tissue volumes or probe dynamic changes repeatedly over prolonged periods. By applying optical frequency domain imaging (OFDI) as an intravital microscopic tool, the technical limitations of multiphoton microscopy can be circumvented providing unprecedented access to previously unexplored, critically important aspects of tumor biology. Using entirely intrinsic mechanisms of contrast within murine tumor models, OFDI is able to simultaneously, rapidly, and repeatedly probe the microvasculature, lymphatic vessels, and tissue microstructure and composition over large volumes. Using OFDI-based techniques, measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy were demonstrated, thereby highlighting the potential of OFDI to facilitate the exploration of pathophysiological processes and the evaluation of treatment strategies.by Ryan M. Lanning.Ph.D
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