Diffuse illumination in fiber bundle microendoscopy for deep tissue imaging

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DESCRIPTION (provided by applicant): Microendoscopic imaging is rapidly becoming an increasingly important field of biomedical imaging. With the ability to provide clinicians histologc information at the point of care during endoscopic procedures, it will be possible to better target surgical biopsies and improve clinical decision-making. One approach employs a flexible, coherent fiber bundle image guide coupled to a simple fluorescent microscope to generate images when in contact with fluorescently labeled epithelial tissues. A significant limitation of this epi-illumination strategy is lack of penetration depth in highly scattering tissues. In order o improve the diagnostic efficacy of this device, we propose a fiber bundle microendoscope imaging system employing a novel off-axis near infrared illumination fiber; the fiber bundle will be used to image the remitted diffusely reflected light. With the use of well-developed Monte Carlo forward models of photon propagation through tissue, we can effectively predict the pattern of diffuse reflection in three dimensions for a given distribution of absorbers in scatterig tissue. The pattern of diffusely reflected light remitted from the surface of tissue and collected y the image guide bundle can be predicted using this modeling approach. Using absorbing materials, it will also be possible to develop layered optical phantoms with discrete heterogeneities that can be quantitatively analyzed using the modified microendoscope. These optical phantoms will consist of systems of increasing complexity, comprising simple absorbing dyes, tuned NIR absorbed gold nanocages, and labeled cells in a collagen suspension. These phantoms will enable clear comparisons between simulated Monte Carlo estimates of performance, and actual experimental measurements. Imaging of diffusely reflected light will demonstrate the use of optically absorbing contrast agents, including molecule-specific nanomaterials, which have been optimized to absorb in the NIR wavelength range. The proposed imaging system will allow the use of these agents using a simple fiber bundle microendoscope device, and enable interrogation of deep structures within epithelial tissues. We believe this approach will greatly broaden the range of available contrast agents to fiber bundle microendoscopes, and significantly improve the capability of this technique across a range of translational applications.