Advances in Optical Coherence Tomography and Confocal Laser Endomicroscopy in Pulmonary Diseases

Abstract

Diagnosing and monitoring pulmonary diseases is highly dependent on imaging, physiological function tests and tissue sampling. Optical coherence tomography (OCT) and confocal laser endomicroscopy (CLE) are novel imaging techniques with near-microscopic resolution that can be easily and safely combined with conventional bronchoscopy. Disease-related pulmonary anatomical compartments can be visualized, real time, using these techniques. In obstructive lung diseases, airway wall layers and related structural remodelling can be identified and quantified. In malignant lung disease, normal and malignant areas of the central airways, lung parenchyma, lymph nodes and pleura can be discriminated. A growing number of interstitial lung diseases (ILDs) have been visualized using OCT or CLE. Several ILD-associated structural changes can be imaged: fibrosis, cellular infiltration, bronchi(ol)ectasis, cysts and microscopic honeycombing. Although not yet implemented in clinical practice, OCT and CLE have the potential to improve detection and monitoring pulmonary diseases and can contribute in unravelling the pathophysiology of disease and mechanism of action of novel treatments. Indeed, assessment of the airway wall layers with OCT might be helpful when evaluating treatments targeting airway remodelling. By visualizing individual malignant cells, CLE has the potential as a real-time lung cancer detection tool. In the future, both techniques could be combined with laser-enhanced fluorescent-labelled tracer detection. This review discusses the value of OCT and CLE in pulmonary medicine by summarizing the current evidence and elaborating on future perspectives.

Keywords: Bronchoscopy; Confocal laser endomicroscopy; Interstitial lung disease; Lung cancer; Obstructive lung disease; Optical coherence tomography.

Fig. 1

Imaging techniques applied to the alveolar compartment with their corresponding resolution and imaging depth. a CLE. b OCT. c HRCT of the chest.

Fig. 2

Overview of the pulmonary anatomical compartments with corresponding OCT and CLE images. Airway wall: OCT, cross-sectional view of airway wall in segmental airway; CLE, pCLE image showing a typical helical ring-like pattern of terminal bronchiole. Lymph nodes: OCT, image in a reactive lymph node; CLE, nCLE image showing abundant lymphocytes in a reactive lymph node. Pleura: OCT, image of subpleural area, pl is indicated by the white arrow; CLE, lamellar organized elastin fibres in the pl as seen with pCLE. Alveolar compartment: OCT, cross-sectional view of alveolar compartment with network of alveolar s; CLE, pCLE image of alveolar compartment showing alveolar septae with rectangular airspaces. Pulmonary vasculature: OCT, cross-sectional view from pulmonary artery; CLE, nCLE image of an mv in a lymph node. OCT, optical coherence tomography; CLE, confocal laser endomicroscopy; Ln, lymph node; pl, pleura; s, septa; mv, microvessel.

Fig. 3

OCT imaging procedures of the airway wall and alveolar compartment (endobronchial OCT; a–c) and pulmonary artery (vascular OCT, d–f). a Bronchoscopic view of an OCT imaging procedure showing the guide sheath and the OCT catheter positioned in the right lower lobe. The metal mark guides the distance of 5.4 cm to the distal tip of the OCT catheter. b OCT image of a normal segmental airway wall showing the airway wall layer identification. c OCT image of the alveolar compartment showing normal alveoli and septae. d Angiography of the left lower lobe pulmonary artery with a stenosis in a chronic thromboembolic pulmonary hypertension (CTEPH) patient (white bracket). e OCT image of a normal proximal pulmonary artery. f OCT image of a pulmonary artery with webs/bands in a CTEPH patient. (Images provided by H.J. Bogaard, MD, PhD; N. van Royen, MD, PhD and M. Beijk, MD, PhD). OCT, optical coherence tomography; P, probe; A, alveolar space; S, septae; E, epithelium; LP, lamina propria; SM, submucosa; C, cartilage.

Fig. 4

pCLE imaging procedures in vivo with corresponding images of the normal alveolar and airway wall compartment (a–c); nCLE imaging in vivo with corresponding images of reactive lymph node capsula and cortex (d–f). a pCLE with the probe (p) positioned in the central airways of the right lower lobe on its way to be advanced to the alveolar compartment. 488 nm laser light reflecting at the airway wall (blue). b pCLE image of the distal airway wall showing a helical ring-like pattern of the terminal bronchiole. c pCLE image of the alveolar compartment showing air-filled alveoli (a) and alveolar septae (s). d nCLE during an EUS procedure for staging of lung cancer, with the probe (p) extending 2 mm distal to the tip of the needle (n). e nCLE image showing elastin fibres (e) of the capsula of a lymph node. f nCLE image showing lymphocytes (l) in a reactive lymph node Wijmans et al. [85]. pCLE, probe based confocal laser endomicroscopy; S, septae; A, alveolar space; nCLE, needle based confocal laser endomicroscopy.

Fig. 5

OCT images of the anterior segment (LB3) of the left upper lobe directly after ronchial thermoplasty (BT) treatment. a Normal, non-directly-BT-treated distal airway area. b BT-treated airway area with peribronchial oedema. c BT-treated airway area showing epithelial sloughing. d Corresponding reconstructed pullback of the airway (540 2D images, total length of 5.4 cm; Goorsenberg et al. [41]). P, probe.

Fig. 6

Endosonography guided nCLE of a mediastinal lymph node metastasis of a tumour in the left upper lobe. a PET-CT scan showing fludeoxyglucose-avid lymph node station 4 L, and the primary lung tumour (T). b EUS image showing an enlarged lymph nodes at station 4 L. c Real-time nCLE image of lymph node station 4 L showing large pleomorphic cells and dark clumps recognized as malignant cells (M). d Fine needle aspirate showing malignant cells of squamous cell carcinoma (Wijmans et al. [26]). 10, lymph node station 10 L (left); Aa, ascending aorta; Ad, descending aorta.

Fig. 7

pCLE images of the alveolar compartment in a patient with a fibrotic NSIP. a HRCT image showing diffuse reticulation and bronchi(ol)ectasis. b pCLE image showing an increased density of alveolar elastin fibre intact network. c pCLE image showing an increased density of thickened alveolar elastin fibre network with loss of normal architecture Wijmans et al. [85]. P, probe.