Non-linear multimodal mircoendoscopy for lung cancer pathology

肺癌是癌症相关死亡的主要原因（约28%）。该建议解决了肺癌高危人群管理中的两个主要挑战：A)外周肺病变的鉴别诊断，B)中央支气管发育不良病变的检测。目前的技术，如低剂量CT和标准白光支气管镜，可以显示发育不良病变，但其检测恶性组织的特异性很差。因此，迫切需要以微创的方式对检测到的病变进行准确的原位分类。我们建议优化、验证和整合互补的非线性光学技术，包括两个或多个二次谐波产生（SHG）、三次谐波产生（THG）、相干反斯托克斯拉曼散射（CARS）和2光子自身荧光（TPF），用于无标记的原位微成像。我们假设，将非线性内镜微成像与超薄扫描纤维支气管镜（一种新兴的颠覆性医疗技术）相结合，将显著提高可疑肺病变（包括周围结节）鉴别诊断的准确性，尤其是特异性，从而实现对恶性组织的靶向局部破坏。

Lung cancer is the leading cause (~28%) of cancer-related deaths. This proposal addresses two major challenges in the management of individuals at high-risk for lung cancer: A) differential diagnosis of peripheral lung lesions, and B) detection of dysplastic lesions in the central bronchus. Current technologies, such as low-dose CT and standard white-light bronchoscopy, can image dysplastic lesions but their specificity for detecting malignant tissue is very poor. Hence, there is an urgent need to classify detected lesions in situ accurately and in a minimally-invasive way. We propose to optimize, validate and integrate complementary non-linear optical techniques, including two or more of second harmonic generation (SHG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS) and 2-photon autofluorescence (TPF), for label-free in situ microimaging. We hypothesize that non-linear endoscopic microimaging, integrated into ultrathin scanning-fiber bronchoscopy (an emerging disruptive medical technology), will significantly increase the accuracy, and particularly the specificity, of differential diagnosis of suspicious lung lesions, including peripheral nodules, and thereby enable targeted local destruction of malignant tissue.