Fiber Probe designs for Epithelial Precancer Detection

描述（由申请人提供）：一种令人兴奋的用于上皮癌前检测的新方法是紫外可见（UV-VIS）荧光光谱。这种技术使用已经存在于组织中的生物分子的内源性荧光作为对比源。最近的研究表明上皮癌前病变的内源性荧光对比是深度依赖的。目前用于组织荧光光谱的光纤探针几何形状体积平均为上皮组织的内源性荧光。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。这项工作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中深度依赖的内源性荧光对比。这项工作将通过(1)数值（蒙特卡罗）建模研究，(2)合成组织幻影的试点测试，以及(3)动物模型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在临床环境中实施第二代原型的开发提供可行性和指导的令人信服的证据。新型角度照明探针的开发将为研究生物组织中深度依赖的荧光提供一种灵敏和特异的工具。此外，拟议的研究将提供关于体内癌前上皮组织内源性荧光深度依赖性变化的新信息，这可以提高目前的诊断准确性。此外，该技术可以扩展到表征基于外源性荧光标记的深度相关光学对比度，从而在其他医学应用中具有实用价值，例如监测药物输送和摄取。

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.