Diagnosis of Cervical & Vulvar Precancers

据估计，仅在美国就有4，400人死于这种疾病，2001年将诊断出12，900例新的侵袭性宫颈癌病例。 现有的筛查和检测技术，巴氏涂片和阴道镜检查，有几个缺陷，防止有效的管理，否则可控的疾病。 一种具有改进的灵敏度和特异性的自动化诊断，可以允许“看和治疗”方案，将显著改善疾病的管理。 光谱学可以提供正常和非正常组织的自动化、快速和非侵入性表征。 特别是，拉曼光谱可用于提供早期疾病的准确鉴别诊断。初步结果表明，使用拉曼光谱诊断宫颈癌前病变的潜力，并将其应用于检测外阴疾病。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，灵敏度和特异性分别为91%和90%，明显优于荧光光谱。更重要的是，来自最初的13名患者的体内研究结果表明，1可以在体内测量来自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（具有与体外观察到的光谱相似的光谱）。 因此，该提议寻求通过提供组织生物化学和病理学的实时、自动化、非侵入性信息来开发用于宫颈癌前病变的鉴别诊断的实时、光学方法。 此外，该提案寻求将该技术的能力扩展到包括外阴疾病。 本课题的具体目标如下：（1）研究活体宫颈组织的拉曼特征。 (2)开发诊断算法，将正常和非癌前组织与癌前组织分开。 (3)使用显微光谱学，细胞化学分析和建模研究观察到的光谱特性差异的基础。(4)对开发的算法进行回顾性和前瞻性评估，以获得其性能估计。(5)评估使用光学光谱学检测外阴疾病的可行性，并验证该技术检测外阴癌前病变的性能。 (6)开发软件接口，以实现数据采集和自动化，并提供实时诊断，并开发紧凑的临床拉曼系统，以减少系统的规模，同时保持其准确性。当这些目标实现时，将产生一种获得宫颈癌前病变的实时、非侵入性检测的方法，这将有助于以高灵敏度和特异性立即管理该疾病。 此外，潜在的翻译应用拉曼光谱到其他器官，特别是在外阴，将进行评估。

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.