High Resolution Optical Coherence Tomography for Early Airway Cancer Detection

描述（申请人提供）：背景：肺癌是美国癌症死亡的主要原因。新型高分辨率内镜的发展对支气管内恶性肿瘤的准确诊断、分期和治疗至关重要。快速采集高分辨率柔性光纤和刚性探头光学相干断层扫描（OCT）的最新进展为内窥镜实时近组织学水平光学成像提供了潜力，从而大大推进了气道癌的检测、诊断和治疗方法。将内窥镜OCT应用于气道诊断和治疗将是一项重大进步，需要：1）开发二维和三维MEMS内窥镜探头，2）改善采集时间、分辨率和对比度，3）硬件和技术优化的转化临床前研究，4）用于证明OCT检测气道癌症的能力和验证的临床患者研究。该资助提案重点关注针对特定肺癌应用的实时高分辨率内窥镜OCT技术的开发和临床研究，其中明确定义了对柔性和刚性高分辨率光学内窥镜的需求：1）评价和评估支气管内癌症边缘，以及2）评估改进的支气管内癌症检测可行性。宗旨和目标：本研究计划的总体目标是开发高分辨率三维功能性OCT（F-OCT）内窥镜，并评估其用于患者气道早期癌症检测和评估的能力。具体目标是：1）进一步开发i）小直径（1 mm）光纤MEMS和ii）用于刚性支气管镜检查的内窥镜三维网格OCT探头。刚性探头也可用于胸腔镜检查和其他内窥镜检查应用）。2)将F-OCT技术用于肺癌诊断，并确定OCT用于气道癌症诊断的灵敏度和特异性。3)在临床研究中将联合收割机OCT与荧光内窥镜技术相结合，以检测支气管镜下气道肿瘤，与组织学相比具有较高的诊断特异性研究设计：用于检测气道恶性肿瘤边缘和早期气道癌症的柔性光纤和刚性内窥镜探头原型将在临床前研究中针对支气管镜和内窥镜成像应用进行优化，然后在临床研究中检测疑似气道恶性肿瘤患者的癌症。相关性：该项目将开发功能齐全的实时近显微分辨率气道成像方法，并证明其在改善患者早期气道癌症诊断方面的有效性。这种将新的工程成像理念扩展到治疗中的做法，也应该能够实现一系列其他肺部和非肺部内窥镜成像应用

DESCRIPTION (PROVIDED BY APPLICANT): Background: Lung cancer is the leading cause of cancer death in the US. Development of novel high resolution endoscopy is essential for more accurate diagnosis, staging, and treatment of endobronchial malignancy. Recent advances in rapid acquisition high-resolution flexible fiberoptic and rigid probe optical coherence tomography (OCT) offer the potential for endoscopic real-time near histologic level optical maging to substantially advance detection, diagnostics, and treatment approaches to airway cancer. Adaptation of endoscopic OCT to airway diagnostics and therapeutics will be a major advance that requires: 1) development of 2 and 3 dimensional MEMS endoscopic probes, 2) improved acquisition times, resolution, and contrast, and 3) translational pre-clinical studies for hardware and technique optimization, and 4) clinical patient studies for demonstration of capabilities and validation of OCT for airway cancer detection. This grant proposal focuses on advancing development and clinical investigation of real-time high- resolution endoscopic OCT technology directed at specific lung cancer applications where the need for flexible and rigid high-resolution optical endoscopy is well-defined: 1) evaluation and assessment of endobronchial cancer margins, and 2) assessment of improved endobronchial cancer detection feasibility. Objectives and Aims: The overall objectives of this research proposal are to develop high resolution 3- dimensional functional OCT (F-OCT) endoscopy and evaluate its capabilities for airway early cancer detection and assessment in patients. The Specific Aims are: 1) Further the development of i) small diameter (1mm) fiberoptic, MEMS, and ii) endoscopic 3-D grid OCT probes for rigid bronchoscopy. The rigid probes will also be usable for thoracoscopy and other endoscopy applications). 2) Translate F-OCT technology to diagnosis of lung cancer and to determine OCT sensitivity and specificity capabilities for airway cancer diagnosis. 3) Combine OCT with fluorescence endoscopic technologies in clinical studies to detect bronchoscopic airway tumor with high diagnostic specificity compared to histology Study Design: Flexible fiberoptic and rigid endoscopic probe prototypes for detecting airway malignancy margins and early airway cancers will be optimized for bronchoscopic and endoscopic imaging applications in pre clinical studies, then in clinical studies to detect cancer in patients with suspected airway malignancy. Relevance: This project will develop fully functional real-time near microscopic resolution airway imaging methods and demonstrate their effectiveness in improving early airway cancer diagnosis in patients. This extension of novel engineering imaging ideas to the treatment should also enable a range of other pulmonary and non-pulmonary scope imaging applications