Probe-Based Confocal Light Endomicroscopy and the Optical Biopsy

Optical biopsy eliminates traditional biopsy risks

Probe-Based Confocal Light Endomicroscopy and the Optical Biopsy

By Sonali Sethi, MD, Joseph Cicenia, MD, and Marie Budev, DO, MPH

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Transbronchial biopsy is one of the most important, albeit risky, medical procedures performed after lung transplantation. It is the least invasive way to assess for acute cellular rejection of the lung allograft but is accompanied by the risk of pneumothorax and bleeding. The consequences of these complications can be particularly severe in single-lung transplant recipients since the remaining native lung may not provide sufficient reserve to maintain the patient if the allograft is compromised.

An evolving diagnostic option

Probe-based confocal light endomicroscopy (pCLE) is an evolving technique that permits acquisition of real-time microscopic images of the lung parenchyma at an alveolar level. Based on preliminary studies regarding the utility of this new technology, Cleveland Clinic’s lung transplant and bronchoscopy teams are collaborating to determine whether optical biopsies using pCLE can be used to diagnose acute cellular rejection, ideally obviating the need for transbronchial biopsies in this high-risk patient group.

How it works

pCLE is based on the principle of illuminating tissue with a lowpower laser and then detecting fluorescent light reflected from the tissue. Using confocal principles, the laser is focused at a specific depth; the light reflected back from that plane is refocused and able to pass through the pinhole confocal aperture, which minimizes scattered light from above and below the plane of interest, increasing spatial resolution. Using inherent autofluorescent properties of tissue, laser scanning can be done at excitatory wavelengths, allowing visualization of target tissue such as elastin, collagen and leukocytes.

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pCLE is performed using Mauna Kea Technologies’ Cellvizio® system (Mauna Kea Technologies, Paris). Cellvizio is an endomicroscopy system that generates optical biopsies by using a flexible catheter carrying tens of thousands of optical fibers to scan tissue. The system provides physicians with instantaneous microscopic images of tissue through minimally invasive techniques. Images of the lung parenchyma generated by this system prompted intense interest in applying this technique to a wide variety of pulmonary disorders.

Optical vs. traditional biopsy

Lung transplant histologic grading is based on guidelines published by the Lung Rejection Study Group in 1990 and revised in 2007. Grading is based exclusively on the location and extent of lymphocytic infiltration around vessels within the lung interstitium. If these patterns can be visualized using pCLE, then it may become possible to use optical biopsies in evaluating for rejection, eliminating the risk of traditional biopsy.

We recently completed enrollment of 200 lung transplant recipients in a prospective study comparing pCLE image acquisition and interpretation with simultaneously obtained transbronchial biopsies in the diagnosis of acute cellular rejection. Data are now being analyzed with the goals of:

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  1. Identifying image characteristics that correlate with rejection
  2. Determining the performance characteristics (e.g., sensitivity, specificity, positive and negative predictive value) of pCLE images in diagnosing rejection
  3. Developing a novel grading system of acute rejection based on images rather than histology

Enhanced capabilities

We anticipate that the imaging capabilities of pCLE will be further enhanced in the near future with the introduction of specific molecular fluorescent probes that can target particular matrix components (e.g., collagen), cell lines or pathogens (e.g., bacteria). This may not only improve the diagnostic utility of pCLE in the transplant population, but also facilitate wider application of the technique to answer questions related to other pulmonary disorders.

Dr. Sethi is a member of the Department of Pulmonary Medicine and can be reached at 216.445.1631 or   Dr. Cicenia is a member of the Department of Pulmonary Medicine and can be reached at 216.445.8606 or   Dr. Budev is the Medical Director of Lung Transplantation and can be reached at 216.444.3194 or