Diffuse illumination in fiber bundle microendoscopy for deep tissue imaging

描述（由申请人提供）：显微内窥镜成像正迅速成为生物医学成像的一个日益重要的领域。在内窥镜检查过程中，能够在护理点为临床医生提供组织学信息， 手术活检和改进临床决策。一种方法采用与简单荧光显微镜耦合的柔性相干纤维束图像引导，以在与荧光标记的上皮组织接触时生成图像。这种落射照明策略的显著限制是在高度散射的组织中缺乏穿透深度。为了提高该装置的诊断效果，我们提出了一种光纤束显微内窥镜成像系统，该系统采用一种新型的离轴近红外照明光纤，光纤束将用于对漫反射光进行成像。利用成熟的光子在组织中传播的Monte Carlo正向模型，我们可以有效地预测在散射组织中给定吸收体分布的三维漫反射模式。利用这种建模方法，可以预测从组织表面发出并由图像引导束收集的漫反射光的图案。使用吸收材料，它也将有可能开发分层光学幻影与离散的异质性，可以使用修改后的显微内窥镜进行定量分析。这些光学幻影将由越来越复杂的系统组成，包括简单的吸收染料，调谐NIR吸收金纳米笼，和胶原蛋白悬浮液中的标记细胞。这些幻影将使性能的模拟Monte Carlo估计值与实际实验测量值之间能够进行清晰的比较。漫反射光的成像将展示光学吸收造影剂的使用，包括分子特异性纳米材料，其已被优化以在NIR波长范围内吸收。所提出的成像系统将允许使用这些代理使用一个简单的纤维束显微内窥镜设备，并使询问上皮组织内的深层结构。我们相信这种方法将大大拓宽纤维束显微内窥镜可用造影剂的范围，并显着提高这种技术在一系列平移应用中的能力。

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.