Browsing by Author "Gao, Liang"

Now showing 1 - 8 of 8
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    Clinical cancer diagnosis using optical fiber-delivered coherent anti-stokes ramon scattering microscopy
    (2012) Gao, Liang; Wong, Stephen T. C.
    This thesis describes the development of a combined label-free imaging and analytical strategy for intraoperative characterization of cancer lesions using the coherent anti-Stokes Raman scattering imaging (CARS) technique. A cell morphology-based analytical platform is developed to characterize CARS images and, hence, provide diagnostic information using disease-related pathology features. This strategy is validated for three different applications, including margin detection for radical prostatectomy, differential diagnosis of lung cancer, as well as detection and differentiation of breast cancer subtypes for in situ analysis of margin status during lumpectomy. As the major contribution of this thesis, the developed analytical strategy shows high accuracy and specificity for all three diseases and thus has introduced the CARS imaging technique into the field of human cancer diagnosis, which holds substantial potential for clinical translations. In addition, I have contributed a project aimed at miniaturizing the CARS imaging device into a microendoscope setup through a fiber-delivery strategy. A four-wave-mixing (FWM) background signal, which is caused by simultaneous delivery of the two CARS-generating excitation laser beams, is initially identified. A polarization-based strategy is then introduced and tested for suppression of this FWM noise. The approach shows effective suppression of the FWM signal, both on microscopic and prototype endoscopic setups, indicating the potential of developing a novel microendoscope with a compatible size for clinical use. These positive results show promise for the development of an all-fiber-based, label-free imaging and analytical platform for minimally invasive detection and diagnosis of cancers during surgery or surgical-biopsy, thus improving surgical outcomes and reducing patients' suffering.
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    Development of Image Mapping Spectrometer (IMS) for hyperspectral microscopy
    (2011) Gao, Liang; Tkaczyk, Tomasz S.
    A snapshot hyperspectral imaging device - Image Mapping Spectrometer (IMS) - has been developed for hyperspectral microscopy. The IMS replaces the camera in a digital imaging system, allowing one to add high speed snapshot spectrum acquisition capability to a variety of imaging modalities, e.g. microscopy, endoscopy, macroscopic imaging, to maximize the collection speed. The IMS described in this thesis is a parallel acquisition instrument that captures a hyperspectral datacube without scanning. It also allows" full" light throughput across the whole spectral collection range due to its snapshot operating format. The developments of three generations of the IMS (low sampling prototype, high sampling IMS, ruggedized IMS)have been reported in this thesis. Two illumination methods (filterless full-spectrum and structured illumination) are also developed for the IMS to achieve specific imaging aims. To show the application of the IMS in realtime hyperspectral imaging of live cells, the Calcium and a FRET-based biosensor are monitored simultaneously in ,B-cell dynamics. The imaging results demonstrate that the IMS has become an important spectral imaging modality in the biological imaging applications.
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    Development of image mapping spectrometer (IMS) for hyperspectral fluorescence microscopy
    (2010) Gao, Liang; Tkaczyk, Tomasz S.
    An image mapping spectrometer (IMS) for microscopy applications is presented. Its principle is based on the redirecting of image zones by specially organized thin mirrors within a custom fabricated component termed an image mapper. The demonstrated prototype can simultaneously acquire a 140nm spectral range within its 2D field of view from a single image. The spectral resolution of the system is 5.6nm. The FOV and spatial resolution of the IMS depend on the selected microscope objective and for the results presented is 45x45mu 2 and 0.45mum respectively. The system requires no scanning and minimal post data processing. In addition, the reflective nature of the image mapper and use of prisms for spectral dispersion make the system light efficient. Both of the above features are highly valuable for real time fluorescent-spectral imaging in biological and diagnostic applications.
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    Image mapping spectrometers
    (2014-02-18) Tkaczyk, Tomasz S.; Kester, Robert T.; Gao, Liang; Rice University; United States Patent and Trademark Office
    Devices and methods for hyperspectral and multispectral imaging are discussed. In particular, Image Mapping Spectrometer systems, methods of use, and methods of manufacture are presented. Generally, an image mapping spectrometer comprises an image mapping field unit, a spectral separation unit, and a selective imager. Image mapping spectrometers may be used in spectral imaging of optical samples. In some embodiments, the image mapping field unit of an image mapping spectrometer may be manufactured with surface shaped diamond tools.
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    Image mapping spectrometry: calibration and characterization
    (Society of Photo-Optical Instrumentation Engineers, 2012) Bedard, Noah; Hagen, Nathan; Gao, Liang; Tkaczyk, Tomasz S.
    Image mapping spectrometry (IMS) is a hyperspectral imaging technique that simultaneously captures spatial and spectral information about an object in real-time. We present a new calibration procedure for the IMS as well as the first detailed evaluation of system performance. We correlate optical components and device calibration to performance metrics such as light throughput, scattered light, distortion, spectral image coregistration, and spatial/spectral resolution. Spectral sensitivity and motion artifacts are also evaluated with a dynamic biological experiment. The presented methodology of evaluation is useful in assessment of a variety of hyperspectral and multi-spectral modalities. Results are important to any potential users/ developers of an IMS instrument and to anyone who may wish to compare the IMS to other imaging spectrometers.
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    Nanoshells in vivo imaging using two-photon excitation microscopy
    (2010) Gao, Liang; Dickinson, Mary E.
    This thesis describes the development and optical characterization of near infrared (NIR) gold nanoshells for the use as luminescent contrast agents for applications in small animal blood vessel imaging. Two types of gold-silica nanoshells excitable by NIR lasers are investigated: Type 1 nanoshells can be excited with a sub-mum NW laser, whereas Type 2 nanoshells can be excited with a NW laser in the micrometer range. Using NIR microscopy as an imaging platform, ex vivo and in vivo experiments are conducted to determine the efficacy of these nanoshells as suitable contrast agents. Specifically, individual particles of Type 1 nanoshells are successfully imaged and shown to provide bright optical contrast for blood vessel imaging both ex vivo and in vivo, while the Type 2 nanoshells are clearly imaged within the blood vessels ex vivo. These positive results suggest a promising possibility of developing a new class of contrast agents for deep tissue imaging and improving the imaging depth of NIR imaging techniques.
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    Real-time hyperspectral fluorescence imaging of pancreatic b-cell dynamics with the image mapping spectrometer
    (The Company of Biologists Ltd, 2012) Elliott, Amicia D.; Gao, Liang; Ustione, Alessandro; Bedard, Noah; Kester, Robert; Piston, David W.; Tkaczyk, Tomasz S.
    The development of multi-colored fluorescent proteins, nanocrystals and organic fluorophores, along with the resulting engineered biosensors, has revolutionized the study of protein localization and dynamics in living cells. Hyperspectral imaging has proven to be a useful approach for such studies, but this technique is often limited by low signal and insufficient temporal resolution. Here, we present an implementation of a snapshot hyperspectral imaging device, the image mapping spectrometer (IMS), which acquires full spectral information simultaneously from each pixel in the field without scanning. The IMS is capable of real-time signal capture from multiple fluorophores with high collection efficiency (,65%) and image acquisition rate (up to 7.2 fps). To demonstrate the capabilities of the IMS in cellular applications, we have combined fluorescent protein (FP)-FRET and [Ca2+]i biosensors to measure simultaneously intracellular cAMP and [Ca2+]i signaling in pancreatic b-cells. Additionally, we have compared quantitatively the IMS detection efficiency with a laser-scanning confocal microscope.
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    Snapshot advantage: a review of the light collection improvement for parallel high-dimensional measurement systems
    (Society of Photo-Optical Instrumentation Engineers, 2012) Hagen, Nathan; Kester, Robert T.; Gao, Liang; Tkaczyk, Tomasz S.
    The snapshot advantage is a large increase in light collection efficiency available to highdimensional measurement systems that avoid filtering and scanning. After discussing this advantage in the context of imaging spectrometry, where the greatest effort towards developing snapshot systems has been made, we describe the types of measurements where it is applicable. We then generalize it to the larger context of high-dimensional measurements, where the advantage increases geometrically with measurement dimensionality.