In vivo probe‐based confocal laser endomicroscopy in chronic interstitial lung diseases: Specific descriptors and correlation with chest CT

Abstract

Background and objective: Probe-based confocal laser endomicroscopy (pCLE) enables in vivo microimaging of the distal lung, during bronchoscopy. This study aims at identifying pCLE descriptors of chronic interstitial lung diseases (ILD), their correlations with chest HRCT and assessing inter-observer agreement. Methods: pCLE was performed in 21 healthy volunteers (HV) and 59 non-smoking ILD patients, including 19 patients with idiopathic pulmonary fibrosis (IPF) or asbestosis, 15 with connective tissue disease-associated ILD (CTD-ILD), 17 with sarcoidosis and 8 with hypersensitivity pneumonitis (HP). pCLE descriptors were identified in ILD on the basis of comparison with HV. Results: Nine pCLE descriptors were more frequent in ILD compared to HV, with good inter-observer agreement, including fluorescent bronchiolar cells (sarcoidosis, CTD-ILD and HP), fluorescent alveolar cells (CTD-ILD and HP), small alveolar entrance rings (IPF or asbestosis and CTD-ILD), enlarged axial elastic fibres (IPF or asbestosis), septal fibres (IPF or asbestosis, CTD-ILD and HP), disorganized acinar network and rigid acinar network (IPF or asbestosis and CTD-ILD), dense elastic network (IPF or asbestosis) and alveolar fluorescent nodular structures (in sarcoidosis) (P < 0.01, Fisher's exact test, all comparisons). The distribution of nodules on computed tomography (CT) appeared to correlate with pCLE alveolar nodular structures, rigid acinar network and septal fibres, while reticulations were associated with septal fibres and disorganized or dense acinar network; ground-glass opacities on CT with small alveolar entrances, rigid elastic network and septal fibres; and honeycombing with septal fibres. Conclusion:In the four groups of ILD studied, 9 pCLE descriptors are described, which appear specific and reproducible, and correlate with chest HRCT patterns. Clinical trial registration: NCT00377338 at ClinicalTrials.govProbe-based confocal laser endomicroscopy (pCLE) enables to image the acinar and alveolar areas at the microscopic level in vivo during flexible bronchoscopy. This study provides reproducible pCLE descriptors of idiopathic pulmonary fibrosis (IPF), asbestosis, connective-tissue disease-related interstitial lung diseases (ILD), sarcoidosis and hypersensitivity pneumonitis, which can be used to conduct prospective and follow-up studies.

In Vivo Endomicroscopy of Lung Injury and Repair in ARDS: Potential Added Value to Current Imaging

“…Of note, while traditionally relatively high in adult human lungs, this spontaneous autofluorescence is low to almost undetectable in young rat lung tissues depending on the setting and type of CLE device in use (see below). Additional contrast and information can be gained by the topical or systemic administration of optical fluorescent probes (a few are FDA-approved for human use: e.g., fluorescein, indocyanin green (ICG), methylene blue (MB), cresyl violet) [51,52] or fluorophore-bound macromolecules (e.g., albumin or moderate-to-high molecular weight polysaccharides such as dextran) to visualize and monitor microcirculation and possible real-time extravascular fluid leakage [19,52,53] (Figure 2) which is an essential component of ARDS. Additionally, agglutinins or specific antibodies fragments can specifically enhance the information provided by endomicroscopy imaging [52,54].…”

Novel exploratory data in interstitial lung disease

“…report on the use of probe‐based confocal laser endomicroscopy (pCLE) to identify morphological abnormalities apparent on direct visualization of alveoli and terminal bronchioles in patients with ILD (e.g. presence of fluorescent cells in bronchiolar areas and increased density of alveolar elastic fibres) . Fourteen variables, selected based on preliminary observations in ILD patients and healthy volunteers, were detectable with good to excellent inter‐observer agreement (with kappa values ranging from 0.66 to 0.97).…”

Automated evaluation of probe-based confocal laser endomicroscopy in the lung

“…To date, we know of no other quantitative analyses for the intricacies of a structure such as the presented structural connectivity value. Other observed structural changes [30] such as alveolar mouth size and increase of fluorescent were not taken into consideration in the presented methods.…”

“…Previous studies have focused on expert observer evaluation [14] or manual post processing methods [30,31] when comparing different elastin of the alveoli. The presented method instead offers quantitative values where the whole structure inside the FOV can be evaluated.…”

“…Since pCLE is an in-vivo imaging technique complementing bronchoscopy, it does not suffer the same increase of risk associated with invasive techniques such as biopsy and could be used to examine multiple sections. So far, procedures performed in multiple studies have shown no severe side effects other than minor bleeding in 3 out of 42 patients [13,30] making it ideal for longitudinal studies.…”