Fiber Probe designs for Epithelial Precancer Detection

描述(由申请人提供)：一种令人兴奋的新方法正在开发中，用于检测上皮癌前病变是紫外线-可见(UV-VIS)荧光光谱学。这项技术使用组织中已经存在的生物分子的内源荧光作为对比的来源。最近的研究表明，上皮性癌前病变的内源性荧光对比度是深度相关的。目前用于组织荧光光谱的光纤探头几何形状--上皮组织中的内源性荧光体积平均化。我们的假设是，能够检测上皮组织深度分辨荧光的光纤探针将增强上皮癌前病变的内源性荧光对比度。本研究的目标是开发一种新型的角度照明光纤探针，以利用上皮癌前病变组织中随深度变化的内源荧光对比度。这项拟议的工作将通过(1)数值(蒙特卡罗)建模研究，(2)对合成组织模体的初步测试，以及(3)动物模型中上皮癌前病变的荧光光谱，来证明这种新方法的可行性和有效性。该项目的成功完成将为第二代原型的开发提供令人信服的可行性证据和指导，以便在临床环境中实施。这种新型角度照明探头的开发将为研究生物组织中的深度相关荧光提供一种灵敏而特异的工具。此外，拟议的研究将产生关于活体癌前上皮组织内源性荧光随深度变化的新信息，这可能会提高目前诊断的准确性。此外，这项技术还可以扩展到基于外源荧光标记的深度相关光学对比度的表征，从而在其他医学应用中具有实用价值，如药物输送和摄取的监测。

DESCRIPTION (provided by applicant): An exciting new modality under development for epithelial precancer detection is ultraviolet-visible (UV-VIS) fluorescence spectroscopy. This technique uses as its source of contrast, the endogenous fluorescence of biological molecules that are already present in the tissue. Recent studies have shown that the endogenous fluorescence contrast in epithelial precancers is depth-dependent. Current fiber-optic probe geometries used for tissue fluorescence spectroscopy volume-average the endogenous fluorescence in epithelial tissues. Our hypothesis is that a fiber-optic probe that can detect depth-resolved fluorescence from epithelial tissues will enhance the endogenous fluorescence contrast in epithelial precancers.The goal of the proposed work is to develop a novel angled illumination fiber-optic probe to exploit the depth-dependent endogenous fluorescence contrast in epithelial precancers. The proposed work will demonstrate the feasibility and effectiveness of this novel approach through (1) numerical (Monte Carlo) modeling studies, (2) pilot testing on synthetic tissue phantoms, and (3) fluorescence spectroscopy of epithelial precancers in an animal model. Successful completion of this project will provide compelling evidence of feasibility and guidance in the development of a second-generation prototype for implementation in a clinical setting. The development of the novel angled illumination probe will result in a sensitive and specific tool for investigating depth- dependent fluorescence in biological tissues. Additionally, the proposed studies will yield new information about the depth-dependent changes in the endogenous fluorescence of precancerous epithelial tissues in vivo, which could improve upon current diagnostic accuracy. Furthermore, this technology can be extended to characterize the depth-dependent optical contrast based on exogenous fluorescent markers and thus have utility in other medical applications such as monitoring of drug delivery and uptake.