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.
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