Multispectral Imaging for Oral Cancer Detection

口腔癌是一个重大的健康问题。所有口腔癌患者的总体5年生存率仅略高于50%；对于晚期疾病患者，30年来生存率一直保持在30-40%或更低。患有早期疾病的患者有更好的治愈机会和良好的功能预后，但即使在这个国家，大多数患者仍然存在晚期肿瘤。早期发现可以改善口腔癌患者的预后，但早期发现的临床工具的敏感性和特异性有限。因此，需要确定有效的筛查手段和早期癌症诊断，以提高早期发现的努力。本提案的目标是开发一种新的技术，多光谱数字显微（MDM）成像，用于口腔肿瘤的无创检测。MDM是一种新型的数码显微镜，可以提供高分辨率的组织彩色图像。它可以在两种模式下工作：(1)它可以成像从组织反射的光的颜色，(2)它可以用来成像组织在单色光照射下产生的自身荧光。我们的研究表明，癌变的过程会引起上皮细胞和支持基质的光学特性的变化。我们以前的工作仅限于取样小的、活检大小的组织区域，这可以用铅笔大小的光纤探针进行评估。在这个提议中，我们将测试一个假设，即在癌变过程中产生的生物化学和组织形态的变化可以使用多光谱数字显微镜实时成像。在目的1中，我们将在一项小型临床研究中比较MDM成像与标准白光检查评估口腔病变的能力。在目的2中，我们将评估MDM成像与标准白光检查相比描绘口腔癌和不典型增生周围粘膜边缘的能力。在这两项试验中，标准组织病理学评估将被用作金标准。在Aim 3中，我们将根据我们使用MDM成像的结果开发初步诊断算法，并确定这些算法在非侵入性区分非典型增生和早期癌与良性病变和正常粘膜的敏感性和特异性。此外，我们将确定在未来大规模临床试验中测试的最佳波长组合。本研究的成功完成将确定MDM成像作为临床工具改善口腔肿瘤的检测和监测的可行性。

DESCRIPTION (provided by applicant): Oral cancer is a major health problem. Overall five-year-survival rates for all oral cancer patients are barely over 50%; for patients with advanced stage disease survival rates have remained at 30-40% or less for thirty years. Patients with early disease have better chances for cure and good functional outcome, but even in this country, most patients still present with advanced tumors. Early detection improves outcomes for oral cancer patients, yet clinical tools for early detection have limited sensitivity and specificity. Thus, identification of effective means of screening and early cancer diagnosis is needed to improve early detection efforts. The goal of this proposal is to develop a new technology, multispectral digital microscopic (MDM) imaging, for non-invasive detection of oral neoplasia. The MDM is a new type of digital microscope, which provides high-resolution color images of tissue. It can operate in two modes: (1) it can image the color of light reflected from tissue, and (2) it can be used to image the autofluorescence produced by tissue when illuminated with monochromatic light. Our group has shown that the process of carcinogenesis produces changes in the optical properties of epithelial cells and the supporting stroma. Our previous work has been limited to sampling small, biopsy-sized areas of tissue, which can be assessed with a pencil-sized fiber optic probe. In this proposal, we will test the hypothesis that changes in biochemistry and tissue morphology produced during carcinogenesis can be imaged in real time using multi-spectral digital microscopy. In Aim 1 we will compare the ability of MDM imaging to that of standard white light examination for assessment of oral lesions in a small clinical investigation. In Aim 2, we will assess the ability of MDM imaging compared to standard white light examination to delineate peripheral mucosal margins of oral carcinoma and dysplasia. In both trials, standard histopathologic evaluation will be used as the gold standard. In Aim 3, we will develop preliminary diagnostic algorithms based on our results using MDM imaging, and determine the sensitivity and specificity of these algorithms to non-invasively distinguish dysplasia and early carcinoma from benign lesions and normal mucosa. In addition, we will determine the optimal wavelength combinations to be tested in future large-scale clinical trials. Successful completion of this research will determine the feasibility for MDM imaging as a clinical tool to improve detection and monitoring of oral neoplasia.