Fiber-optic confocal imaging for in vivo detection and diagnosis of precancerous lesions

This dissertation describes the design, analysis, and construction of a confocal fiber optic reflectance imaging system. The intended application of the device is in vivo detection and diagnosis of precancerous lesions in epithelial tissue.; The efficacy of in vivo confocal imaging for the intended application depends upon the ability of the technique to penetrate the full thickness of the epithelium. Previously it was thought that the penetration depth was fundamentally limited by the background signal from photons originating outside the focal volume. Experiments with tissue phantoms have shown that the background scattering is not the limiting factor with the proper choice of confocal pinhole diameter.; The ability of confocal imaging to image in vivo cell anatomy has previously been carried out in pigmented tissue where melanin within the cells provides the confocal signal and image contrast. Confocal images of amelanotic breast cancer cells resolved the structure within the nuclei as well as the gross cellular structure. The potential of contrast agents for improving in vivo confocal imaging was also demonstrated.; A design analysis of the fiber optic system revealed the complexity and potential problems in its construction. To simplify the construction, the development of the instrument was broken into three stages; each one increasing the complexity of the instrumentation. The initial stage was assembling the core confocal optics into a point detection system with micron resolution and high sensitivity. In the second stage, a confocal microscope was constructed by including the optics and electronics of a scanning system into the first system. The assembled microscope produced images of physiological structure with micron resolution at 15 frames per second. In the final stage, a series of lenses were designed and constructed to incorporate the fiber optic bundle into the second system and to control the specular reflections from the face of the fiber optic bundle. Controlling the specular reflections was the primary engineering challenge in the construction of the device. The assembled fiber optic system demonstrated the potential for clinical use in the near future.