Raman Probe for Bronchial Premalignant Lesions

描述(申请人提供)：该项目的目标是通过检查由光纤拉曼探头确定的被观察组织的分子成分的附加信息来提高诊断的敏感性，特别是自体荧光内窥镜的特异性。这种组合的仪器将首先使用自体荧光成像来快速识别可能发育不良或癌变的组织区域。在标准的支气管镜检查程序中，取该区域的一小部分组织样本，用钳子穿过内窥镜狭窄的活检通道。在这个项目中，光纤拉曼探头将首先通过这个活组织检查通道，并轻轻地按在可疑组织区域。1秒的830纳米窄带光脉冲将通过位于探头远端的中央光纤和透镜组件被引导到组织上。探头尖端的长通滤光片将阻挡后向散射的830 nm激发波长，但会将更长波长的组织荧光和拉曼位移的光传递到收集光纤的环中。这些收集光纤将把散射的光带回光谱仪，光谱仪将其分散成特征的拉曼“指纹”光谱。该光谱包含许多与组织中特定分子的浓度相对应的单独的峰。然后，标准的活检将从组织部位取出，并被送到病理实验室进行检查，以寻找异常增生或癌症的证据。该程序将对测量的光谱进行分类，并将它们与病理结果相关联。一旦光谱目录包含了正常、发育不良和癌变组织的指纹样本，就可以开始实时预测病理结果。然而，在预测结果可能可靠之前，需要收集已发现癌症的许多不同阶段的大量光谱。在支气管镜检查过程中使用自体荧光成像已被证明比仅通过白光观察可以提高癌症诊断的敏感性。这意味着很少有真正的癌变或发育异常的组织区域被认为是正常的(癌症的假阴性确定)。另一方面，该方法经常将正常组织归类为癌症(假阳性确定)，这会给患者带来额外的风险，因为不必要的活组织检查、手术过程中浪费的时间和额外的成本。来自拉曼探针的额外信息有望识别出其中许多假阳性部位为真正正常的，从而增加组织特征的特异性。一旦这种方法被证明是有效的，它将降低患者的风险，减少手术所需的时间，并降低不必要的活检成本。

DESCRIPTION (provided by applicant): The goal of this program is to improve the diagnostic sensitivity and especially the specificity of autofluorescence endoscopes by examining additional information on the molecular constituents of the tissue being observed as determined by a fiberoptic Raman probe. The combined instrument will first use autofluorescence imaging to quickly identify areas of tissue which are likely to be dysplastic or cancerous. In a standard bronchoscopy procedure a small sample of tissue from this area would be taken with forceps passed through the narrow biopsy channel of the endoscope. In this program, a fiberoptic Raman probe will first be passed through this biopsy channel and pressed lightly against the suspect area of tissue. A 1-second pulse of narrowband, 830 nm light will be directed onto the tissue through a central fiber and lens assembly at the distal tip of the probe. A long-pass filter in the tip of the probe will block the backscattered 830 nm excitation wavelength but pass the longer wavelength tissue fluorescence and Raman-shifted light into a ring of collection fibers. These collection fibers will carry the scattered light back to a spectrometer which will disperse it into a characteristic Raman "fingerprint" spectrum. This spectrum contains many individual peaks corresponding to the concentration of specific molecules in the tissue. The standard biopsy will then be taken from the tissue site and sent to a pathology lab to be examined for evidence of dysplasia or cancer. This program will catalog the measured spectra and correlate them with the results of pathology. Once the catalog of spectra contains samples of normal, dysplastic and cancerous tissue fingerprints it will be possible to begin to predict, in real-time, what the results of pathology will be. A large number of spectra will need to be collected, however, from many different stages of discovered cancers before the predicted results are likely to be reliable. The use of autofluorescence imaging during bronchoscopy procedures has been shown to improve the sensitivity of cancer diagnosis over that which can be achieved by white light observation alone. This means there are few instances where a truly cancerous or dysplastic area of tissue is seen to be normal (a false negative determination of cancer). On the other hand, the method often classifies normal tissue as cancerous (a false positive determination) which leads to an additional risk to the patient from unnecessary biopsies, wasted time during the procedure and additional costs. The additional information from the Raman probe is expected to be able to identify many of these false positive sites as truly normal, increasing the specificity of the tissue characterization. Once the method is proven to be effective it will reduce patient risk, reduce the time required for procedures and reduce the cost of unnecessary biopsies.