Imaging of human airways by endoscope-compatible dynamic microscopic optical coherence tomography

Cornelia Holzhausen^1,2*Hinnerk Schulz-Hildebrandt³Martin Ahrens^2,4Noah Heldt^2,4Mario Pieper^1,2Heike Biller⁵Sönke Von Weihe⁵David Ellebrecht⁵Mustafa Abdo^2,5Stefan Steurer⁶Christoph Fraune⁶Klaus F Rabe^2,5Gereon Hüttmann^2,4Peter König^1,2

• ¹Institute of Anatomy, University of Lübeck, Lübeck, Germany
• ²Airway Research Center North (ARCN), German Center for Lung Research (DZL), Großhansdorf, Germany
• ³Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, United States
• ⁴Institute of Biomedical Optics, University of Lübeck, Lübeck, Germany
• ⁵LungenClinic Grosshansdorf GmbH, Großhansdorf, Germany
• ⁶Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Introduction: Microscopy is a cornerstone for diagnostics in lung disease but was traditionally restricted to biopsies and explanted tissue. Microscopic optical coherence tomography (mOCT) produces images with microscopic resolution without the need for exogenous makers. As recently demonstrated in excised mouse tissue, the combination with dynamic contrast (dmOCT) generates high contrast images of airway tissue. DmOCT therefore has the potential to be used for virtual biopsies in humans. Methods: To assess the potential of dmOCT combined with endoscopic imaging, we scanned excised human lung tissue through a custom-built endoscope optic and compared the resulting dmOCT images with conventional histologic sections of the same tissue. We also assessed if imaging time can be substantially reduced while keeping sufficient dmOCT image quality. Results: Endoscopic dmOCT successfully visualized the epithelium and subepithelial tissue of human airways including smooth muscle cells and glands The technique detected key structural changes such as inflammatory cell infiltration, basement membrane thickening, epithelial damage, and the transition to carcinoma in situ. In addition, dmOCT distinguished between different morphologies of human lung cancer present in the examined tissue. The image contrast for discriminating these structures remained sufficient even after the acquisition time was reduced to 0.054 s. Discussion: We have shown that dmOCT, when combined with endoscopic optics, reaches the image quality and imaging speed making its use for virtual biopsies in vivo realistic in the future.