Registry Trial to Determine pCLE Image Interpretation Criteria and Preliminary Accuracy in the Lung


About this study

Patients will be enrolled that are undergoing bronchoscopy for diagnosis of discrete lung lesions or for detection of acute rejection following lung transplants. The hypothesis is that bronchoscopy together with probe-based endomicroscopy (pCLE) results in improved and/or incremental diagnostic yield (definitive diagnosis) over conventional bronchoscopy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female ≥ 18 years of age
  • Willing and able to comply with study procedures and provide written informed consent to participate in the study
  • Indeterminate discrete nodule(s) suspicious for cancer scheduled for diagnostic bronchoscopy
  • Newly discovered &/or prior discovered non classified nodules, hard to define based on CT scan
  • Purpose of bronchoscopy is for diagnosis of lesion(s) - can be solitary pulmonary nodule or multiple lesions
  • All lesion locations are acceptable
  • Any patient undergoing clinically indicated bronchoscopies after lung transplantation
  • Patients post transplant showing clinical signs of acute rejection >3 weeks; < 1 year
  • Patient with single or double lung transplant

Exclusion Criteria:

  • Contraindication to short-acting anesthetic agents;
  • Contraindications to transbronchial biopsy
  • Bleeding diathesis;
  • A pacemaker/defibrillator;
  • A diagnosis by other means (sputum cytology, microbiology).
  • Unwilling To Consent
  • Unable To Safely Tolerate A Bronchoscopic Procedure
  • Unwilling To Comply With Surveillance Bronchoscopy Follow Up
  • Chronic Rejection
  • Fungal Disease
  • Ax Histological Assessment Or Incomplete Biopsy Procedure Should Be Considered As A Screen Failure

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Jacksonville, Fla.

Mayo Clinic principal investigator

Francisco Alvarez, M.D.

Closed for enrollment

More information


  • The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R-EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here. Read More on PubMed
  • Bronchoscopy is a minimally invasive method for diagnosis of diseases of the airways and the lung parenchyma. Standard bronchoscopy uses the reflectance/scattering properties of white light from tissue to examine the macroscopic appearance of airways. It does not exploit the full spectrum of the optical properties of bronchial tissues. Advances in optical imaging such as optical coherence tomography (OCT), confocal endomicroscopy, autofluorescence imaging and laser Raman spectroscopy are at the forefront to allow in vivo high-resolution probing of the microscopic structure, biochemical compositions and even molecular alterations in disease states. OCT can visualize cellular and extracellular structures at and below the tissue surface with near histological resolution, as well as to provide three-dimensional imaging of the airways. Cellular and subcellular imaging can be achieved using confocal endomicroscopy or endocytoscopy. Contrast associated with light absorption by haemoglobin can be used to highlight changes in microvascular structures in the subepithelium using narrow-band imaging. Blood vessels in the peribronchial space can be displayed using Doppler OCT. Biochemical compositions can be analysed with laser Raman spectroscopy, autofluorescence or multispectral imaging. Clinically, autofluorescence and narrow-band imaging have been found to be useful for localization of preneoplastic and neoplastic bronchial lesions. OCT can differentiate carcinoma in situ versus microinvasive cancer. Endoscopic optical imaging is a promising technology that can expand the horizon for studying the pathogenesis and progression of airway diseases such as COPD and asthma, as well as to evaluate the effect of novel therapy. Read More on PubMed
  • "Optical biopsy" using bronchoscopic probe-based confocal endomicrosocopy (pCLE) provides real time images of the autofluorescent elastin scaffold of the healthy acinus. Read More on PubMed
  • Because of the low sensitivity of current ERCP-guided tissue sampling methods, management of patients with indeterminate pancreaticobiliary strictures is a challenge. Probe-based confocal laser endomicroscopy (pCLE) enables real-time microscopic visualization of strictures during an ongoing ERCP. Read More on PubMed
  • Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been extensively evaluated. Read More on PubMed
  • The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. Read More on PubMed
  • Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated. Read More on PubMed
  • Fibered confocal fluorescence microscopy (FCFM) is a new imaging modality in bronchoscopy. The purpose of this study was to assess FCFM reliability, interpretation, and to make image-pathologic correlations. Read More on PubMed
  • Fibred confocal fluorescence microscopy, also named probe based confocal laser endomicroscopy (pCLE), is a new endoscopic technique that can be applied for in-vivo microscopic imaging of both upper airways and distal lung structures during bronchoscopy. Read More on PubMed
  • In the past 15 years, new endoscopic methods have been developed in order to improve the detection of early bronchial cancers, with autofluorescence bronchoscopy being the leading technique. However, autofluorescence bronchoscopy is hampered by the low specificity of the fluorescence defect which ranges from 25 to 50%, and its limitation to the proximal bronchial tree from which arise only half of the lung cancers that are currently diagnosed. To overcome these limitations, other techniques emerge including video/autofluorescence bronchoscopy, narrow band imaging, optical coherence tomography, and 'endomicroscopy' using confocal fluorescent laser microscopy. These emerging techniques provide new insight into bronchology, extending the field of exploration from the proximal bronchus down to the most distal part of the lungs, and from macroscopy to in vivo cellular imaging. In the near future, they may enable in vivo, minimally invasive, 'pathological grade' evaluation of abnormal bronchial or parenchymal lung tissue. Whereas promising pioneer work has recently been published, careful assessment is required before these methods find a place in the evaluation strategy of early lung cancer and other lung diseases. Read More on PubMed
  • The aim of the present study was to assess fibred confocal fluorescence microscopy (FCFM) as a tool for imaging the alveolar respiratory system in vivo during bronchoscopy. A 488-nm excitation wavelength FCFM device was used in 41 healthy subjects including 17 active smokers. After topical anaesthesia, the 1.4-mm miniprobe was introduced into the bronchoscope working channel and advanced distally to the alveoli. Morphometric and cellular analyses were performed on selected frames harbouring a minimal compression effect. In vivo acinar microimaging was obtained from each lung segment except for the apical and posterior segments of both upper lobes. Reproducible patterns, corresponding to the elastic framework of the axial and peripheral interstitial systems, were recorded from 192 separate acini. The mean+/-sd thickness of the acinar elastic fibres was 10+/-2.7 microm. Alveolar mouth diameters (mean+/-sd 278+/-53 microm) were normally distributed but appeared smaller in the right upper lobe and right medial basal segment. Lobular microvessels (median diameter 90 microm) were equally distributed throughout the lungs. Alveolar macrophages were not detectable in nonsmokers, whereas a specific tobacco-tar-induced fluorescence was observed in smoking subjects, providing fine details of the alveolar walls and macrophages. A strong correlation was found between the number of cigarettes smoked per day and the amount of large and mobile macrophages observed in vivo, as well as with the intensity of the macrophage alveolitis. Fibred confocal fluorescence microscopy enables accurate exploration of the peripheral lung in vivo in both smokers and nonsmokers. Read More on PubMed
  • The biggest challenge in endoscopic surveillance of Barrett's oesophagus is better detection of neoplasia in mucosa of normal macroscopic appearance. We evaluated in vivo miniprobe confocal laser microscopy (CLM) for the detection of invisible Barrett's neoplasia. Read More on PubMed
  • Due to advances in interventional bronchoscopy, curative treatment has become possible for central type lung cancer if it is detected in the early stage. However, expertise is required to diagnose the extent of tumor invasion and the depth of tumor involvement by conventional white light bronchoscopy alone, but judgement is still subjective. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) has had a large impact on diagnostic bronchoscopy in the past decade and have been employed especially for the diagnosis of central type tumors. Objective evaluation by a comprehensive approach using AFB, EBUS and optical coherence tomography (OCT) enables selection of the optimal therapeutic strategy for central type early lung cancer (CELC). Read More on PubMed
  • Electromagnetic navigation bronchoscopy using superDimension/Bronchus System is a novel method to increase diagnostic yield of peripheral and mediastinal lung lesions. Read More on PubMed
  • Lung nodules are detected very commonly on computed tomographic (CT) scans of the chest, and the ability to detect very small nodules improves with each new generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years or older have pulmonary nodules on CT scans. However, the existing guidelines for follow-up and management of noncalcified nodules detected on nonscreening CT scans were developed before widespread use of multi-detector row CT and still indicate that every indeterminate nodule should be followed with serial CT for a minimum of 2 years. This policy, which requires large numbers of studies to be performed at considerable expense and with substantial radiation exposure for the affected population, has not proved to be beneficial or cost-effective. During the past 5 years, new information regarding prevalence, biologic characteristics, and growth rates of small lung cancers has become available; thus, the authors believe that the time-honored requirement to follow every small indeterminate nodule with serial CT should be revised. In this statement, which has been approved by the Fleischner Society, the pertinent data are reviewed, the authors' conclusions are summarized, and new guidelines are proposed for follow-up and management of small pulmonary nodules detected on CT scans. Read More on PubMed
  • Most lung transplant recipients experience improvement in their underlying pulmonary condition but are faced with the threat of allograft rejection, the primary determinant of long-term survival. Several studies examined predictors of rejection, but few focused on the early period after transplantation. Read More on PubMed
  • To evaluate the sensitivity, specificity, predictive values, and accuracy of thin-section computed tomography (CT) for the diagnosis of acute rejection following lung transplantation and to determine whether any individual CT abnormalities are associated with histopathologically proved acute rejection. Read More on PubMed
  • The Early Lung Cancer Action Project (ELCAP) was designed to evaluate the usefulness of annual computed tomography (CT) screening for lung carcinoma. With the baseline results having been reported previously, the focus of the current study was on the early results of the repeat screenings. Read More on PubMed

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