Diagnosis of Cervical & Vulvar Precancers

据估计，仅在美国就将有4 400人死于这种疾病，2001年将诊断出12 900例侵袭性宫颈癌新病例。现有的筛查和检测技术，如巴氏涂片检查和阴道镜检查，存在一些缺陷，妨碍了对一种本来可以控制的疾病的有效管理。提高敏感性和特异性的自动诊断，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、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，利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。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，最初的13例患者体内研究结果表明，1可以测量体内宫颈组织的拉曼光谱；2拉曼光谱可以识别体内宫颈病变1（光谱与体外观察到的相似）。因此，本研究旨在通过提供实时、自动、非侵入性的组织生化和病理信息，开发一种实时、光学的宫颈癌前病变鉴别诊断方法。此外，本建议旨在扩大该技术的能力，包括外阴疾病。拟议项目的具体目标如下：(1)对体内宫颈组织的拉曼特征进行表征。(2)开发将正常和非癌前组织与癌前组织分开的诊断算法。(3)利用显微光谱学、细胞化学分析和模型研究观察到的光谱特征差异的基础。(4)对所开发的算法进行回顾性和前瞻性评估，以获得对其性能的估计。(5)评估使用光谱学检测外阴疾病的可行性，验证该技术在外阴癌前病变检测中的性能。(6)开发软件接口，实现和自动化数据采集，提供实时诊断，并开发紧凑型临床拉曼系统，以减少系统规模，同时保持其准确性。这些目标一旦实现，将产生一种实时、非侵入性检测宫颈癌前病变的方法，这将有助于以高灵敏度和特异性立即管理该疾病。此外，还将评估将拉曼光谱应用于其他器官，特别是外阴的潜力。

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.