Raman-Guided Bronchoscopy: Feasibility and Detection Depth Studies Using Ex Vivo Lung Tissues and SERS Nanoparticle Tags

Image-guided and robotic bronchoscopy is currently under intense research and development for a broad range of clinical applications, especially for minimally invasive biopsy and surgery of peripheral pulmonary nodules or lesions that are frequently discovered by CT or MRI scans. Optical imaging and spectroscopic modalities at the near-infrared (NIR) window hold great promise for bronchoscopic navigation and guidance because of their high detection sensitivity and molecu-lar/cellular specificity. However, light scattering and background interference are two major factors limiting the depth of tissue penetration of photons, and diseased lesions such as small tumors buried under the tissue surface often cannot be detected. Here we report the use of a miniaturized Raman device that is inserted into one of the bronchoscope channels for sensitive detection of “phantom” tumors using fresh pig lung tissues and surface-enhanced Raman scattering (SERS) nanoparticle tags. The ex vivo results demonstrate not only the feasibility of using Raman spectroscopy for endoscopic guidance, but also show that ultrabright SERS nanoparticles allow detection through a bronchial wall of 0.85 mm in thickness and a 5 mm-thick layer of lung tissue (approaching the fourth-generation air-way). This work highlights the prospects and potential of Raman-guided bronchoscopy for minimally invasive imaging and detection of lung lesions.