Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer

Abstract

IntroductionDiagnosing peripheral lung cancer with the bronchoscope is challenging with near miss of the target lesion as major obstacle. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic tumour visualisation at the needle tip (smart needle).AimTo investigate feasibility and safety of bronchoscopic nCLE imaging of suspected peripheral lung cancer and to assess whether nCLE imaging allows real-time discrimination between malignancy and airway/lung parenchyma.MethodsPatients with suspected peripheral lung cancer based on (positron emission tomography-)CT scan underwent radial endobronchial ultrasound (rEBUS) and fluoroscopy-guided flexible bronchoscopy. After rEBUS lesion detection, an 18G needle loaded with the CLE probe was inserted in the selected airway under fluoroscopic guidance. The nCLE videos were obtained at the needle tip, followed by aspirates and biopsies. The nCLE videos were reviewed and compared with the cytopathology of the corresponding puncture and final diagnosis. Five blinded raters validated nCLE videos of lung tumours and airway/lung parenchyma twice.ResultsThe nCLE imaging was performed in 26 patients. No adverse events occurred. In 24 patients (92%) good to high quality videos were obtained (final diagnosis; lung cancer n=23 and organising pneumonia n=1). The nCLE imaging detected malignancy in 22 out of 23 patients with lung cancer. Blinded raters differentiated nCLE videos of malignancy from airway/lung parenchyma (280 ratings) with a 95% accuracy. The inter-observer agreement was substantial (κ=0.78, 95% CI 0.70 to 0.86) and intra-observer reliability excellent (mean±SD κ=0.81±0.05).ConclusionBronchoscopic nCLE imaging of peripheral lung lesions is feasible, safe and allows real-time lung cancer detection. Blinded raters accurately distinguished nCLE videos of lung cancer from airway/lung parenchyma, showing the potential of nCLE imaging as real-time guidance tool.

Targeted detection of cancer at the cellular level during biopsy by near-infrared confocal laser endomicroscopy

“…Existing NIR imaging modalities can identify tumor at the macroscopic level, but this study demonstrates microscopic NIR identification of cancer cells in vivo. CLE has been previously studied for endoscopic evaluation of nodules in a variety of organ systems 19 , 25 – 27 . Prior work in nCLE imaging has relied upon tissue autofluorescence or reverse-contrast imaging in the far-red spectrum after systemic administration of fluorescein 11 , 18 .…”

“…Fiber-based CLE is an adaptation of conventional microendoscopy technology in which a low-power laser illuminates a tissue of interest and transmits light reflected from the tissue via a flexible optical fiber bundle to generate high-resolution tissue images 17 . Both probe-based CLE (pCLE) and needle-based CLE (nCLE) permit autofluorescence imaging as well as reverse-contrast imaging of tissues after systemic administration of fluorescein 11 , 13 , 18 , 19 . Recent studies conducted by Annema and colleagues have shown the benefit of fluorescein-based nCLE as a diagnostic adjunct in the bronchoscopic diagnosis and staging of lung cancer 13 , 19 .…”

“…Both probe-based CLE (pCLE) and needle-based CLE (nCLE) permit autofluorescence imaging as well as reverse-contrast imaging of tissues after systemic administration of fluorescein 11 , 13 , 18 , 19 . Recent studies conducted by Annema and colleagues have shown the benefit of fluorescein-based nCLE as a diagnostic adjunct in the bronchoscopic diagnosis and staging of lung cancer 13 , 19 .…”

Getting innovative bronchoscopic techniques into real clinical practice

“…To conclude, the study by Kramer et al demonstrates the potential of nCLE imaging technology and will further contribute to the innovative bronchoscopy platforms combining a high tool-in-lesion navigation success and optical endomicroscopy based tissue verification 12. A near microscopy optical biopsy might complement invasive tissue sampling in order to optimise clinical lung nodule management in the near future.…”

“…In their proof-of-principle study, Kramer et al prospectively demonstrated the feasibility of bronchoscopic nCLE imaging, which aids accurate detection of peripheral pulmonary nodules at the needle tip in a selected patients 12. Good quality nCLE-videos were obtained in 24 out of 26 (92%) patients with suspected peripheral lung cancer (final pathological diagnosis of malignancy in 23 patients).…”