Raman Probe for Bronchial Premalignant Lesions

描述（由申请人提供）：本项目的目的是通过检查光纤拉曼探针确定的观察组织分子成分的附加信息，提高诊断灵敏度，尤其是自体荧光内窥镜的特异性。该组合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，将使用穿过内窥镜的狭窄活检通道的镊子从该区域获取少量组织样本。在该程序中，光纤拉曼探针将首先通过该活检通道，并轻轻按压组织的可疑区域。将通过穿刺针远端头端的中心光纤和透镜组件将1秒窄带830 nm光脉冲引导到组织上。探针尖端的长通滤波器将阻挡反向散射的830 nm激发波长，但将较长波长的组织荧光和拉曼位移光传递到收集光纤环中。这些收集光纤将把散射光带回光谱仪，光谱仪将把散射光分散成特征性的拉曼“指纹”光谱。该光谱包含与组织中特定分子的浓度相对应的许多单个峰。然后将从组织部位进行标准活检，并送往病理实验室进行检查，以确定发育不良或癌症的证据。该程序将对测得的光谱进行编目，并将其与病理学结果相关联。一旦光谱目录包含正常、异型增生和癌症组织指纹的样本，就有可能开始实时预测病理学的结果。然而，在预测结果可能可靠之前，需要从发现的癌症的许多不同阶段收集大量光谱。在支气管镜检查过程中使用自体荧光成像已被证明可以提高癌症诊断的灵敏度，超过仅通过白色光观察可以实现的灵敏度。这意味着很少有情况下，组织的真正癌变或发育不良区域被视为正常（癌症的假阴性确定）。另一方面，该方法通常将正常组织分类为癌性的（假阳性确定），这导致患者因不必要的活检、手术期间浪费的时间和额外的成本而面临额外的风险。来自拉曼探针的额外信息预期能够将这些假阳性位点中的许多鉴定为真正正常的，从而增加组织表征的特异性。一旦该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，并减少不必要的活检的成本。

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.