Diagnosis of Cervical & Vulvar Precancers

据估计，仅在美国就有4400人死于这种疾病，2001年将诊断出12900例新的浸润性宫颈癌病例。现有的筛查和检测技术，如巴氏涂片和阴道镜，有几个缺陷，阻碍了对原本可控的疾病的有效管理。具有更高的灵敏度和特异度的自动化诊断将显著改善对疾病的管理，从而能够实现“见即治”方案。光学光谱学可以为正常和非正常组织提供自动、快速和非侵入性的表征。特别是，拉曼光谱可以用来对早期疾病提供准确的鉴别诊断。初步结果表明，使用拉曼光谱诊断宫颈癌前病变并将其应用于外阴疾病的检测是有潜力的。特别是，体外研究表明，拉曼光谱可以区分宫颈癌前病变和所有其他组织类别，灵敏度和特异度分别为91%和90%，明显优于荧光光谱。更重要的是，最初的13名患者的体内研究结果表明，1可以在体内测量宫颈组织的拉曼光谱，以及(2)拉曼光谱可以在体内识别宫颈病变I(光谱与体外观察到的相似)。因此，这项建议寻求开发一种实时的、光学的方法，通过提供实时、自动化、非侵入性的组织生化和病理信息来鉴别诊断宫颈癌前病变。此外，这项建议寻求扩大这项技术的能力，以包括外阴疾病。该项目的具体目标如下：(1)研究活体宫颈组织的拉曼特征。(2)开发诊断算法，将正常和非癌前病变组织与癌前病变组织区分开来。(3)利用显微光谱分析、细胞化学分析和模拟等方法研究光谱特征差异的依据。(4)对开发的算法进行回顾和前瞻性评估，以获得对其性能的估计。(5)评估光学光谱学用于外阴疾病的可行性，并验证该技术用于外阴癌前病变检测的能力。(6)开发软件接口，以实现和自动化数据采集和提供实时诊断，并开发紧凑型临床拉曼系统，以减少系统的规模，同时保持其准确性。这些目标一旦实现，将产生一种获得实时、非侵入性检测宫颈癌前病变的方法，这将促进对这种疾病的高敏感性和特异性的即时治疗。此外，还将评估将拉曼光谱技术应用于其他器官，特别是外阴的可能性。

It was estimated that 4,400 deaths would occur in the United States alone from this disease and 12,900 new cases of invasive cervical cancer would be diagnosed in 2001. Existing screening and detection techniques, the Pap smear and colposcopy, have several deficiencies that prevent efficient management of an otherwise controllable disease. An automated diagnostic with improved sensitivity and specificity that could allow for a "See and Treat" protocol would significantly improve the management of the disease. Optical spectroscopy can provide automated, fast and non-intrusive characterization of normal and non-normal tissues. In particular, Raman spectroscopy can be used to provide accurate differential diagnosis of early disease. Preliminary results indicate the potential of using Raman spectroscopy for the diagnosis of cervical precancers and to translate its application for the detection of vulvar disease. In particular, in vitro studies show that Raman spectroscopy can differentiate between cervical precancers and all other tissue categories with a sensitivity and specificity of 91 percent and 90 percent, significantly better than fluorescence spectroscopy. More importantly, the results from the initial 13 patients studied in vivo, indicate that 1 it is possible to measure Raman spectra from cervical tissue in vivo and (2) Raman spectroscopy can identify cervical lesions in vivo I (with spectra similar to that observed in vitro). Thus this proposal seeks to develop a real-time, optical method for the differential diagnosis of cervical precancerous lesions by providing real-time, automated, non-intrusive information of the tissue biochemistry and pathology. In addition, this proposal seeks to extend the capability of this technique to include vulvar disease. The specific aims of the proposed project are as follows; (1) Characterize Raman signatures of cervical tissues in vivo. (2) Develop diagnostic algorithms that separate normal and non- precancerous tissues from precancerous tissues. (3) Study the basis of observed differences in the spectral characteristics using microspectroscopy, cyto-chemical analysis, and modeling. (4) Conduct retrospective and prospective evaluation of the algorithms developed to obtain estimates of their performance. (5) Assess the feasibility of using optical spectroscopy for vulvar disease and verify the performance capability of this technique for vulvar precancer detection. (6) Develop software interface to implement and automate data acquisition and provide real-time diagnosis and to develop a compact clinical Raman system to reduce the scale of the system while maintaining its accuracy. These objectives when achieved will yield a method of obtaining real-time, non intrusive detection of cervical precancers that will facilitate the immediate management of the disease with high sensitivity and specificity. In addition, the potential of translating the application of Raman spectroscopy to other organs and in the vulva, in particular, will be assessed.