Diffuse illumination in fiber bundle microendoscopy for deep tissue imaging

描述(申请人提供)：显微内窥镜成像正在迅速成为生物医学成像的一个日益重要的领域。有了在内窥镜手术过程中向临床医生提供护理点的组织学信息的能力，将有可能更好地定位 手术活检和改善临床决策。一种方法是使用柔性的、连贯的纤维束图像导向器连接到简单的荧光显微镜上，以在与荧光标记的上皮组织接触时产生图像。这种表观照明策略的一个重要限制是在高散射组织中缺乏穿透深度。为了提高该设备的诊断效率，我们提出了一种新型的离轴近红外照明光纤的光纤束显微内窥镜成像系统，该光纤束将被用来成像被反射的漫反射光。利用发展成熟的光子在组织中传播的蒙特卡罗正演模型，我们可以有效地预测在给定的散射组织中的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反射并由像导束收集的漫反射光的图案。利用吸收材料，还可以开发具有离散异质性的层状光学模体，可以使用改进的显微内窥镜对其进行定量分析。这些光学模体将由越来越复杂的系统组成，包括简单的吸收染料，可调的近红外吸收金纳米笼，以及胶原蛋白悬浮液中的标记细胞。这些模型将使性能的模拟蒙特卡罗估计和实际实验测量之间能够进行明确的比较。漫反射光成像将展示光学吸收造影剂的使用，包括分子特定的纳米材料，它们已被优化为在近红外波长范围内吸收。建议的成像系统将允许使用这些试剂使用简单的纤维束显微内窥镜设备，并能够询问上皮组织内的深层结构。我们相信，这种方法将极大地拓宽纤维束显微内窥镜可用的造影剂范围，并显著提高这项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.