Increasing the diagnostic yield of low-risk bronchial biopsy in the evaluation of

描述（由申请人提供）：肺癌是癌症相关死亡的主要原因，死亡人数超过乳腺癌、前列腺癌和结肠癌的总和。早期诊断对患者的生存至关重要，然而，绝大多数肺部恶性肿瘤只有在症状出现并且癌症已经扩散时才被检测到，此时患者几乎没有治愈的机会。包括CT和支气管镜检查在内的宏观成像方式在增加早期检测方面取得了重大进展;然而，它们不具有诊断恶性肿瘤所需的特异性。诊断必须在显微镜水平上进行，目前只能通过切除活检来完成。不幸的是，用于取回活检样本的低风险支气管镜技术受到低诊断率的阻碍，并且经胸和手术方法具有较高的并发症内在风险。鉴于这些宏观成像平台的假阳性率非常高，因此必须避免高风险程序，并大大提高低风险方法的诊断准确性。在这项提案中，我们的目标是使用新的光学成像工具来局部引导活检部位选择，从而大大提高低风险支气管活检的诊断率， 获得样品用于组织病理学和分子分析。具体而言，我们将开发和翻译偏振敏感光学频域成像（PS-OFDI）系统，以及用于进行气道和外周肺PS-OFDI的新型导管。我们将制定和验证用于评估肺癌病理学PS-OFDI图像的诊断标准，并将开展临床研究，以证明活检率优于传统方法。这项工作将充分利用马萨诸塞州总医院和NinePoint Medical的专业知识、资源和研究人员之间的持续合作关系。已经形成的战略联盟将确保成功翻译和交付强大而强大的新型光学支气管镜工具，这可能会提高支气管活检评估肺癌的诊断率。

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer related death accounting for more deaths than breast, prostate and colon combined. Early diagnosis is critical to patient survival, however the vast majority of lung malignancies are detected only once symptoms arise and the cancer has spread, at which time patients have little chance of cure. Macroscopic imaging modalities including CT and bronchoscopy have made significant strides in increasing early detection; however they do not have the required specificity to diagnose malignancy. Diagnosis must be made on the microscopic level, which at present can only be accomplished with excisional biopsy. Unfortunately, low-risk bronchoscopic techniques for retrieving biopsy samples are hampered by low diagnostic yields, and trans-thoracic and surgical approaches carry higher intrinsic risk of complications. Given the very high false positive rates of these macroscopic imaging platforms it is imperative that high-risk procedures are avoided and the diagnostic accuracy of lower-risk approaches is greatly improved. In this proposal we aim to dramatically increase the diagnostic yield of low-risk bronchial biopsy using novel optical imaging tools to locally guide biopsy site selection ensuring that diagnostic quality samples are obtained for both histopathology and molecular profiling. Specifically, we will develop and translate polarization-sensitive optical frequency domain imaging (PS-OFDI) systems, and novel catheters for conducting PS-OFDI of the airways and peripheral lung. We will develop and validate diagnostic criteria for evaluating the PS-OFDI images of lung cancer pathology, and we will conduct clinical studies to demonstrate the improvement in biopsy yield over conventional approaches. This work will leverage the expertise, resources and ongoing collaborative ties between investigators at Massachusetts General Hospital and NinePoint Medical. Together the strategic alliance already formed will ensure the successful translation and delivery of a powerful and robust new optical bronchoscopy tool that will likely result in an increase in the diagnostic yield of bronchial biopsy for the assessment of lung cancer.