Ultra-Miniature Multi-Modal Endoscopes

描述(申请人提供)：本研究的主要目标是：1)制造能够同时进行漫反射白光成像和荧光成像的超小型内窥镜，以及2)展示这些仪器独特的科学和临床应用。超微型内窥镜的导管将基于现有的纤维束和GRIN透镜技术，但需要沿着中心成像通道进行照明。一种新型的NA共享光学设计，结合了偏振技术、减反射涂层、光谱限制和数据处理，将被用来克服光纤束照明产生的背景信号的固有问题。该系统将采用一种新颖的分瞳概念，实现高灵敏度彩色图像和荧光图像的多模式同时采集。该仪器的开发针对多种科学和临床应用。一个重要的科学应用是对Barrett‘s食道的小鼠模型进行成像。在R21阶段，将开发仪器的概念，将测量小鼠食道的内源性漫反射和自体荧光对比度以优化系统设计，将研究使用外源造影剂增强图像对比度，并将该仪器用于评估小鼠食道的活体成像。假设达到了里程碑，R33阶段将需要建立一个全功能的多模式成像仪器，包括具有必要功能的导管。将在小鼠食道中进行验证研究，以证明该仪器在这一特定应用中的科学实用性和有效性。更多的研究将通过体外人体组织标本和动物模型进行，以评估拟议的临床应用在支气管和血管成像方面的可行性和有效性。

DESCRIPTION (provided by applicant): The primary objectives of this research are: 1) to build ultra-miniature endoscopes with the capability for simultaneous diffuse white-light reflectance imaging and fluorescence imaging, and 2) to demonstrate unique scientific and clinical applications for these instruments. The catheter of the ultra-miniature endoscope will be based on existing fiber bundle and GRIN lens technology, but will require illumination down the central imaging channel. A novel NA-sharing optical design combined with polarization techniques, anti-reflection coatings, spectral confinement, and data processing will be used to overcome the inherent problem of background signal generated from illumination down the fiber bundle. A novel split-pupil concept will be employed in the system to achieve simultaneous multi-modal acquisition of color images and fluorescence images with high sensitivity. The development of the instrumentation is aimed at multiple scientific and clinical applications. One important scientific application is imaging the esophagus of a mouse model of Barrett's esophagus. During the R21 phase, the instrument concepts will be developed, endogenous diffuse reflectance and autofluorescence contrast will be measured in the mouse esophagus to optimize the system design, image contrast enhancement using exogenous contrast agents will be investigated, and the instrument will be used to evaluate in vivo imaging in mouse esophagus. Assuming the milestones are met, the R33 phase will entail building a fully functional multi-modal imaging instrument including catheters with the necessary functionality. A validation study will be carried out in mouse esophagus to demonstrate the scientific utility and efficacy of the instrument for this particular application. Additional studies will be carried with ex-vivo human tissue specimens and animal models to evaluate the feasibility and efficacy of the proposed clinical applications in bronchial and vascular imaging.