Lizzy Wijmans

Optical coherence tomography and confocal laser endomicroscopy in pulmonary diseases

Purpose of review Current imaging techniques (X-ray, computed tomography scan, ultrasound) have limitations in the identification and quantification of pulmonary diseases, in particular, on highly detailed level. The purpose of this review is to provide an overview of the current knowledge of innovative light- and laser-based imaging techniques that might fill this gap. Recent findings Optical coherence tomography (OCT) and confocal laser endomicroscopy (CLE) are high-resolution imaging techniques, which, combined with bronchoscopy, provide ‘near histology’ detailed imaging of the airway wall, lung parenchyma, mediastinal lymph nodes, and pulmonary vasculature. This article reviews the technical background of OCT and CLE, summarizes study results, and discusses its potential clinical applications for various pulmonary diseases. Summary Although investigational at the moment, OCT and CLE are promising innovative high-resolution optical imaging techniques for the airway wall, lung parenchyma, mediastinal lymph nodes, and pulmonary vasculature. Clinical applications might contribute to improved disease identification and quantification, guidance for interventions/biopsies, and patient selection for treatments. Development of validated identification and quantification image-analysis systems is key for the future application of these imaging techniques in pulmonary medicine.

Validation of needle-based confocal laser endomicroscopy

We congratulate Benias et al. for their work on needle-based confocal laser endomicroscopy (nCLE) for the evaluation of malignant lymph nodes [1]. Confocal laser endomicroscopy is a laser-based optical technique that enables real-time visualization of tissue on a microscopic level. In combination with endoscopic ultrasound (EUS), the nCLE technique can possibly be helpful in identifying the optimal sampling location or even evolve to a real “optical biopsy” tool in the diagnosis and staging of pancreatic [2] and lung cancer [3]. At this stage, however, the nCLE technique is still investigational and requires validation in different tissue types. nCLE image interpretation by relating the videos to pathology is essential. Ideally, a one-to-one comparison of the nCLE images with the corresponding histology is indicated. In the Benias et al. paper, the assessed lymph nodes were punctured using a 19 G needle under EUS guidance and subsequently imaged with nCLE [1]. Several questions remain regarding the actual image interpretation and analysis. In the methods section, it is stated that the reviewers compared the nCLE imaging with histological core biopsies. Was a core biopsy always present, or were cell blocks and cytological smears also used as the reference standard? Although the histology images of Figs. 1a, 2a, and 6a are very illustrative, they do not seem to correlate directly with the case discussed. A direct comparison of nCLE images to the pathological substrate is a key component in understanding the diagnostic possibilities and limitations of this novel optical imaging technique. Could the authors clarify how they specifically performed this assessment? Clearly recognizable lymph node structures such as the cortex (Fig. 3a) and the capsule (Fig. 1b) are shown on nCLE imaging. However, the lymphoid follicles (Fig. 3b) and the sarcoid-type granuloma (Fig. 3e) seem very similar on appearance. What criteria are used to distinguish the lymphoid node follicles from epithelioid histiocytes? An official statement of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the utilization of advanced endoscopic imaging in gastrointestinal endoscopy was recently published in Endoscopy [4]. The development of validated classification systems is advocated to support the use of optical diagnosis in combination advanced endoscopic imaging [4]. The authors have made a first step in describing nCLE characteristics of normal and malignant involved lymph nodes. However, larger sample numbers and validation of the characteristics are essential to evaluate the value of the nCLE technique, as an add-on to EUS-guided fine-needle aspiration, for lymph node analysis.

Reply: Exploring Endomicroscopy in the Field of Pulmonology

With interest, we read the letter of Dr. Shulimzon regarding our clinical imaging case of an endoscopic ultrasound–guided real-time “optical biopsy” of a pulmonary tumor (1). In his letter, the history of microscopy and the concept of confocal laser endomicroscopy (CLE) are described. Needle-based confocal laser endomicroscopy (nCLE) enables visualization of tissue at a near-microscopic level, thereby acting as a real-time microscope. Recently, Shulimzon and colleagues described in a proof-of-principle study the use of nCLE for transthoracic computed tomography–guided biopsy of lung and mediastinal tumors (2). The novelty of the case under discussion is the application of nCLE in conjunction with endosonography (1). This is of potential clinical importance, as endosonography is the technique of choice for mediastinal tissue staging of lung cancer (3). Dr. Shulimzon underlines the importance of carefully assessing the added value of novel technologies over existing ones, and we fully agree with him. At this stage, needle-based tumor imaging by nCLE (visualization in a real-time fashion of tumor cells) is explorative. Further research is needed before the nCLE technique can be useful in clinical practice for the guidance of optimal needle placement. CLE is a promising novel imaging technique that needs further exploration to determine its value in pulmonary medicine. In our opinion, it is of particular importance to develop universally accepted criteria that relate CLE images to pathology that can be used internationally by CLE users. Recently, a technical review was published as an official statement of the European Society of Gastrointestinal Endoscopy that addresses the use of advanced endoscopic imaging in gastrointestinal endoscopy. The use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging is recommended (4). Currently, classifications systems for the CLE technique in pulmonary medicine are rare. To achieve this, we propose the following three-step approach: (1) identification of CLE imaging characteristics of nondiseased tissue compared with pathology; (2) identification of CLE imaging characteristics of diseased tissue compared with pathology; and (3) testing of the proposed CLE criteria by blinded observers. The realization of an internationally accepted validated classification system of CLE imaging is a necessary step to realize a real “optical biopsy.” n