Integrated Bi-FOV Endoscope for Detection of Precancer

描述(申请人提供)：这项建议的主要目标是建立一种双视野内窥镜，用于癌症前和癌症早期检测，结合两种：(1)高分辨率和(2)低分辨率成像系统。出于这一提议的目的，我们将这种仪器称为“双视野内窥镜”。在低倍放大率下，内窥镜将成像几平方厘米的区域，以识别可疑病变。然后，这些区域将以更高的分辨率进行成像，以可视化亚细胞的形态和分子特征，从而明确识别癌前病变。简而言之，我们将克服高分辨率光学系统中小视场的限制，将其与大视场内窥镜耦合在一起。我们成像系统的高分辨率部件是一个多模微型显微镜“4M装置”。4M设备的功能是利用光与多种形式的组织相互作用来成像体内的形态和生物化学，从而产生更好地描绘肿瘤的工具。在这笔赠款中，我们将使用其中一种模式--结构照明的反射成像。在我们前期的研究中，我们设计并组装了集成微型显微镜的原型，展示了该系统在癌前组织检测中的潜力。在这个方案中，我们将扩展这个4M设备的视场，集成CMOS检测和数字信号处理能力，以实现组织的亚细胞分辨率实时图像。4M设备系统将经过改进，然后与用于初步选择样本区域的低分辨率/大视野内窥镜相结合。我们将设计和组装一个小型化的光学系统，视场为15 mm，横向分辨率为60微米。用于4M设备的相同平台(微型光学台-MOT)技术(LIGA-深度X射线光刻)和探测器(CMOS阵列)将应用于新的低分辨率内窥镜。使用相同的基本MOT方法将使整个系统更紧凑、组装简单和成本效益更高。在开发双视野内窥镜的同时，我们将在一系列逐渐复杂的生物模型系统中测试每个系统组件以及低分辨率和高分辨率内窥镜，最终将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.