Fiber Probe designs for Epithelial Precancer Detection

描述（由申请人提供）：一种正在开发的用于上皮癌前病变检测的令人兴奋的新模式是紫外-可见（UV-VIS）荧光光谱法。该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其对比源。最近的研究表明，内源性荧光对比在上皮癌前病变是深度依赖性的。目前用于组织荧光光谱的光纤探针几何形状体积平均上皮组织中的内源性荧光。我们的假设是，一个光纤探针，可以检测从上皮组织的深度分辨荧光将增强内源性荧光对比度在上皮precancer.The拟议的工作的目标是开发一种新的角度照明光纤探针，利用深度依赖内源性荧光对比度在上皮precancer。拟议的工作将通过（1）数值（蒙特卡罗）建模研究，（2）合成组织模型的试点测试，和（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临床环境中实施的第二代原型的开发提供令人信服的可行性和指导证据。新型角度照明探针的发展将为研究生物组织中的深度依赖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体内癌前上皮组织内源性荧光的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荧光标记的深度依赖性光学对比度，从而在其他医学应用中具有实用性，例如监测药物递送和摄取。

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.