By Benjamin Ross
July 11, 2018 | A study recently published in Transplantation provides the results of a multi-centered trial conducted by the Mayo Clinic that purported the effectiveness of optical biopsies as safe alternatives to invasive biopsies in the case of diagnosing acute cellular rejection (ACR) in lung transplant patients.
The study, titled “Diagnosis of Acute Cellular Rejection Using Probe-Based Confocal Laser Endomicroscopy in Lung Transplant Recipients: a Prospective, Multi-Center Trial” (DOI: 10.1097/TP.0000000000002306), describes how analyzing perivascular cellularity (PVC) through probe-based confocal laser endomicroscopy (pCLE) was a feasible and reproducible criterion for the assessment of ACR in vivo.
Cesar Keller, a doctor at the Mayo Clinic’s Lung Transplant Program in Jacksonville, Florida and first author of the study, told Diagnostics World that the most challenging aspect of the study was taking the time to interpret what they were looking for in the acquired images.
“We realized that it was indeed possible to recognize vascular structures with acute cellularity in a fashion similar to what regular biopsies show,” Keller said. However, “it takes a little bit of a learning curve for all investigators to have a comfort level during the analysis. You have to learn a certain level of skill with seeing the images and recognizing the patterns.”
According to Keller, the Mayo Clinic used Cellvizio, a pCLE platform developed by Mauna Kea, for the duration of the 2-year study.
“What we were doing was trying to use the Cellvizio probe in order to get in vivo images of the alveolar and vascular structures, and trying to correlate those findings with what later would be a standard diagnosis of [ACR],” Keller said. “The purpose was to see if there was a correlation that we could see immediately after seeing the images that could help us discern if a given patient was or was not having this acute rejection in the transplanted lung.”
Acquiring immediate images of the lung in vivo is invaluable, said Keller, because the lung is a difficult organ to successfully transplant. Unlike other transplanted organs like the heart or kidney, the lung engages with a person’s environment in close proximity, making it easily susceptible to ACR or other complications.
Keller said the transplanted lung is also at risk when using the standard methods of diagnosing ACR, invasive transbronchial biopsies.
“[With biopsies,] essentially you cut out tiny pieces of lung,” Keller explained. “With that process you could perforate the lung, causing pneumothorax or pulmonary bleeding.”
Twenty-four patients who had undergone a lung transplant within the prior year, and who were scheduled for diagnostic biopsies through the Mayo Clinic, were enrolled for the study.
Overall, 30 pCLE procedures were performed, which showed ACR in 8 of the patients. Keller said the next step will be confirming whether the results of this study can be reproduced on a larger scale.
“We have to understand we have more than 300 years where microscopes were used to look at tissues, and certainly ever since lung transplant technology started to evolve in the 1980s a lot of pathologists have dedicated themselves to find exactly what is the pattern that you see in lung biopsies showing acute rejection,” Keller said. “This technology has only been available for a few years. So we’re really starting to learn what the potential of this technology is.”
The pCLE platform is a tool that provides immediately-available images that could help decide whether a patient has ACR. “But, after all is said and done, it’s only 24 patients,” said Keller.
The upshot, according to Keller, is the capability and potential of the Cellvizio probe itself.
Keller believes the future of this technology will be its ability to evolve into a software that will do image analysis and pattern recognition in a computerized form, instead of relying on the researchers to interpret the data for themselves.
“I think the final word on how this technology may or may not be applicable to lung transplantation is yet to come. It’ll be exciting to see how this technology continues to evolve.”