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

Abstract

Introduction: Diagnosing 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).

Aim: To 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.

Methods: Patients 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.

Results: The 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).

Conclusion: Bronchoscopic 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.

Keywords: bronchoscopy; histology/cytology; imaging/CT MRI etc; lung cancer; non-small cell lung cancer.

Conflict of interest statement

Competing interests: MdB has nothing to disclose. TR has nothing to disclose. TvL has nothing to disclose. PB has nothing to disclose. LW has nothing to disclose. JTA reports financial and material support from Mauna Kea Technologies during the conduct of this investigator initiated study. TK reports use of the research grant from Mauna Kea Technologies obtained by Professor JTA.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Study flow diagram. *In total, three patients (10 nCLE videos) were excluded from the video selection of the training and validation sessions due to poor nCLE image quality and a non-malignant final diagnosis (organising pneumonia). #Of every nCLE-imaged lung tumour at least one video was included in the validation set to make the selection most representative. nCLE, needle-based confocal laser endomicroscopy.

Figure 2

(A) Chest CT scan with a lung tumour in the left upper lobe (arrow) and (B) radial endobronchial ultrasound image with an eccentric tumour visualisation. (C) Preloading of the needle:after adjusting the luer lock (L) on the 18G Broncus needle, the confocal miniprobe is advanced through the luer lock, positioning the tip of the probe (P) 4 mm past the needle tip (N). (D) In-vivo needle-based confocal laser endomicroscopy image at the tip of the needle showing real-time pleomorphic enlarged tumour cells (T) representing a sarcoma metastasis.

Figure 3

(A–C) Real-time needle-based confocal laser endomicroscopy (nCLE) imaging of different lung tumours demonstrating the two ‘static’ nCLE malignancy criteria (enlarged pleomorphic cells and dark clumps) and the ’dynamic’ phenomenon of directional streaming (online example). (D–F) Corresponding cytology of the fine needle aspirate representing squamous cell carcinoma, adenocarcinoma and sarcoma metastasis. (G–I) Schematic display of malignant nCLE features.

Figure 4

(A–D) Real-time needle-based confocal laser endomicroscopy (nCLE) imaging at the needle tip showing three nCLE airway criteria (elastin fibres, bronchial epithelium and still image) and the alveoli of the lung parenchyma. (E–H) Histology (E, G and H) and cytology (F) of the different structures in the airway and lung parenchyma. (I–L) Schematic display of the airway (I–K) and lung parenchyma (L) nCLE features. (A) Autofluorescent elastin fibre bundles (indicated in E by arrow) along the lumen of the airway (indicated in E by L*). (B) Small homogeneous and equally distributed cells representing the bronchial epithelium (F). (C) Still nCLE image as the result of the CLE-probe being advanced in the lumen of a larger airway (indicated in G by L*) without touching the airway wall. (D) Autofluorescent alveoli with a hexagonal architecture (H). Scale bar: (A–F and H) 20 µm and (G) 50 µm.