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    Widefield micro-camera integrated into the objective lens of a reflectance confocal microscope for concurrent image registration
    (Montana State University - Bozeman, College of Engineering, 2023) Aist, Joseph Nicholas; Chairperson, Graduate Committee: David L. Dickensheets
    With millions of new skin disease cases reported annually, non-invasive imaging methods have been developed to diagnose skin disease accurately. Reflectance confocal microscopes (RCM) have led these new technologies with high sensitivity and specificity. However, current methods use multiple devices: a digital camera, a dermoscope, and an RCM, which are not co-registered. Therefore, locating small, microscopic RCM fields-of-view (0.5x0.5 mm) at specific suspicion sites within the larger dermoscopic field-of-view (10x10 mm) is extremely difficult. This 'blind' RCM imaging results in lower and more variable diagnostic accuracy, particularly sensitivity, where positive and negative predictive values can drop by up to 30%. Our team has designed a new objective lens with an integrated micro-camera to deliver a concurrent widefield image of the skin surface surrounding the location of microscopic RCM imaging. The widefield image can be used directly to provide context for RCM or can be registered to a previously stored high-resolution clinical image to show where RCM imaging is occurring. In this thesis, the micro-camera is characterized and tested in laboratory and clinical settings. In addition, this thesis investigates a co- and cross-polarized micro-camera and LED system. It compares them to the non-polarized system to explore whether the cross-polarized version enhances feature contrast and enables better dermoscopic imaging. Non-polarized, co-polarized, and cross-polarized mock-up probes of the objective lens with a micro-camera were designed and built for testing. Images of resolution targets, color charts, and skin were taken to obtain modulation transfer function (MTF) measurements, color analysis data, and representative skin images. The results showed improvement in the MTF for the cross- polarized probe when compared to the co- and non-polarized probes. It was also found that the polarization of the imaging system did not significantly affect the color quality of the images. When tested by scientists at Memorial Sloan Kettering Cancer Center, sub-surface features not seen with the co- and non-polarized probes were observed with the cross-polarized probe. The cross-polarized probe suppressed the surface reflections, allowing for sub-surface information to be captured.
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    MEMS 3-dimensional scanner with SU-8 flexures for a handheld confocal microscope
    (Montana State University - Bozeman, College of Engineering, 2018) Liu, Tianbo; Chairperson, Graduate Committee: David Dickensheets
    The conventional method for diagnosing skin cancer is to perform a biopsy followed by pathology. However not only are biopsies invasive and likely to leave permanent scarring, they also sample the body sparsely. Fortunately, a non-invasive method of imaging called confocal laser scanning microscopy has shown great potential to replacing invasive biopsies. Confocal microscopy can use light to achieve high-resolution imaging of cells that lie underneath the surface of the skin. However, the large size of current confocal microscopes limits their application to all but the most accessible sites. In this dissertation, I address the miniaturization of confocal microscopy through the development of a new microelectromechanical systems scan mirror that can scan a focused beam in three dimensions. The scanner has a 4 mm aperture, and has the capability to replace all of the bulky beam scanners and focus mechanisms that contribute to the large size of current confocal microscopes. The fabrication of the scanner explores the use of the polymer SU-8 for its mechanical structures. The gimbal mirror has demonstrated scan angles in excess of plus or minus 3° mechanical for lateral scanning, and its deformable surface provided controllable deflection up to 10 microns for focus control. This newly developed scanner was integrated into a confocal system to test its imaging capabilities. The device demonstrated high-resolution scanning with simultaneous focus adjustment suitable for the next generation of miniaturized confocal laser scanning microscopes.
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