Integrated Bi-FOV Endoscope for Detection of Precancer

描述（由申请人提供）：本提案的主要目标是构建一种用于癌前和早期癌症检测的双FOV内窥镜，结合两种：（1）高分辨率和（2）低分辨率成像系统。出于本提案的目的，我们将该仪器称为“双视野内窥镜”。在低放大率下，内窥镜将成像几平方厘米的区域，以识别可疑病变。这些区域将以更高的分辨率成像，以可视化亚细胞形态和分子特征，从而明确识别癌前病变。简而言之，我们将通过将高分辨率光学系统与大FOV内窥镜耦合在一起来克服小FOV对于高分辨率光学系统的限制。我们的成像系统的高分辨率组件是一个多模态微型显微镜“4 M设备”。4 M器械的功能是利用光与组织的相互作用，以多种方式对体内形态学和生物化学进行成像，从而产生可更好地描绘肿瘤的工具。在本研究中，我们将使用其中一种方式-结构照明反射成像。集成微型显微镜的原型是在我们以前的研究中设计和组装的，在那里我们展示了这种系统用于癌前组织检测的潜力。在本提案中，我们将扩展该4 M设备的FOV，集成CMOS检测和数字信号处理功能，以实现真实的时间的组织亚细胞分辨率图像。将对4 M器械系统进行优化，然后与用于初步选择样本区域的低分辨率/大FOV内窥镜结合使用。我们将设计和组装一个小型化的光学系统，视场为15毫米和60微米的横向分辨率。与4 M器械相同的平台（微型光学台- MOT）技术（LIGA -深X射线光刻）和探测器（CMOS阵列）将应用于新型低分辨率内窥镜。使用相同的基础MOT方法将使整个系统更紧凑，组装简单，成本效益高。在开发Bi-FOV内窥镜的同时，我们将在一系列越来越复杂的生物模型系统中测试每个系统组件以及耦合的低分辨率和高分辨率内窥镜，最终在切除的肿瘤标本中进行实验。

DESCRIPTION (provided by applicant): The major goal of this proposal is to build a dual FOV endoscope for pre-cancer and early cancer detection combining two: (1) high and (2) low resolution imaging systems. For the purpose of this proposal we call this instrument the "Bi-FOV Endoscope". At low magnification, the endoscope will image an area of several square centimeters, in order to identify suspicious lesions. These areas will then be imaged at higher resolution, to visualize the subcellular morphologic and molecular features which definitively identify precancerous lesions. In short, we would overcome the limitation of a small FOV for high resolution optical systems by coupling it together with a large FOV endoscope. The high resolution component of our imaging system is a Multi-Modal Miniaturized Microscope "4M Device". The function of the 4M Device is to utilize the interaction of light with tissues in many modalities to image morphology and biochemistry in vivo, yielding tools that provide better delineation of tumors. In this grant, we will use one of these modalities - reflectance imaging with structured illumination. The prototype of the integrated miniaturized microscope was designed and assembled in our previous research, where we showed the potential of this system for pre-cancerous tissue detection. In this proposal, we will extend the FOV of this 4M device, integrate CMOS detection and digital signal processing capabilities to achieve sub-cellular resolution images of tissue in real time. The 4M Device system will be refined and then coupled with a low resolution / large FOV endoscope used for preliminary selection of a sample region. We will design and assemble a miniaturized optical system with FOV of 15 mm and 60 microns lateral resolution. The same platform (Miniaturized Optical Table - MOT) technology (LIGA - deep X-ray lithography) and detector (CMOS array) as used for the 4M Device will be applied to a new, low resolution endoscope. Using the same base MOT approach will make entire system more compact, simple in assembly and cost effective. In parallel with the Bi - FOV Endoscope development, we will testing each system component, as well as the coupled low and high resolution endoscopes in a series of progressively more complex biological model systems, culminating with experiments in excised tumor specimens.