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UBC Theses and Dissertations

Versatile multimodality microscopy for in vivo skin characterization and skin disease diagnosis Wu, Zhenguo


Various optical imaging technologies have been used to optically biopsy the skin tissue to make an early diagnosis in vivo and noninvasively. However, compared to conventional gold standard- histology, these techniques often have limitations in resolution, contrast, the field of view (FOV), depth correlation, and practicability. This thesis presents a versatile multimodality microscopy system for in vivo and non-invasive skin evaluation at the bedside by providing three-dimensional tissue information with high resolution and multi-contrast in an extended field of view. It integrates reflectance confocal microscopy, two-photon excitation microscopy, second harmonic generation microscopy, and confocal Raman spectroscopy to provide tissue information with high resolution and complementary contrast. Besides horizontal-plane imaging, fast-vertical plane imaging is realized, and it further enabled the development of a motion tolerant y-stacking volumetric imaging method for acquiring three-dimensional tissue information in an extended length. For practical clinical application, the system is integrated with a white light imaging channel using the microscopy objective to take a macro image to guide the microscopic imaging. The use of an articulated mirror arm gives the system flexibility to measure different body sites. The system is tested on healthy skin and skin cancers. With false colour coding of different image modalities, various layers of the healthy skin could be differentiated in the vertical view of the acquired volume while the horizontal plane shows tissue morphology with sub-cellular resolution. For skin cancers, three-dimensional features of the basal cell carcinoma, squamous cell carcinoma and melanoma were described. With volume large enough to cover the cancer margin, we observed the gradual changes of cellular morphology and tissue structure from normal to cancer three-dimensionally. In addition to imaging, the thesis also demonstrates the potential of using the system to do the imaging-guided precise treatment using blood vessel closure on a mouse model as an example. The system is also capable of performing imaging-guided point of interest micro-Raman spectroscopy to provide biochemical information. All the results demonstrate the success of the versatile multimodality microscopy system and its usefulness for skin evaluation and skin disease diagnosis at the bedside. Supplementary materials available at: http://hdl.handle.net/2429/77382.

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