A minimally invasive imaging device that generates high-resolution images of nasal airways, including the cilia and mucus, allows researchers to visualize changes at the cellular level that underlie cystic fibrosis (CF) in patients.
The data confirms that mucus dehydration and abnormalities of the airway’s epithelia, as well as loss of cilia — hair-like structures that have diverse motility and sensory functions — are major hallmarks of the disease.
The findings of “Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies” were published in the journal Science Translational Medicine.
Dehydration of the airway and mucus abnormalities are thought to result in slower mucus transport in people with CF. This may result in obstruction of the airways, chronic infections, and unregulated inflammation. However, much of this research has used animal models and cell cultures, rather than the direct study of patients. This is especially true for research at the cellular level.
Now, a team led by researchers at Harvard Medical School, and the Wellman Center for Photomedicine at Massachusetts General Hospital, has developed a new imaging device which uses a technique known as micro-optical coherence tomography. The technique offers high-resolution of approximately 1 micrometer — approximately a 50th of the size of a human hair. That allows cellular details to be studied in vivo (in the body).
The technique uses a imaging catheter approximately 2 mm in diameter. The very small size makes it minimally invasive, and allows the nasal passages to be studied without requiring the patients to be sedated.
Researchers used the imaging device to compare the nasal airways of 10 CF patients and 10 healthy people (controls). They looked at cilia — the hair-like structures lining nasal airways — and mucus clearance.
Study participants reported minimal discomfort, and there were no clinical relevant adverse complications of the imaging procedure.
Results showed that the mucus in the nasal airways of CF patients was more dehydrated, and moved significantly more slowly, than in healthy controls. This affected the speed of the cilia — their beat had a significantly lower pace.
Moreover, a layer that lies between the cells in the airways and the mucus, called periciliary liquid layer, was depleted in people with CF — a hallmark of airway dehydration.
Taken together, these results favor “a longstanding but controversial hypothesis that dysregulated mucus hydration is a key feature that underlies CF pathogenesis,” the researchers said.
“It’s unprecedented to see this pathophysiology dynamically in living patients. It will allow us to begin to understand things we never even knew were there,” Guillermo Tearney, MD, PhD, the co-principal investigator of the study and professor at Harvard Medical School, said in a press release written by Bob Shepard.
A greater number of inflammatory cells were found in the mucus of CF patients, and their mucus was more viscous, or syrupy. Moreover, there were areas of cilia and the underlying epithelium that had been lost.
“We thought they [cilia] were there but just not functioning well,” Tearney said, “but in places, they were just completely gone.”
Researchers hope that the new imaging device will enable the earlier diagnosis and monitoring of CF. It also may be used to optimize treatment by allowing analysis of any changes in the airway microanatomy.
“Visualizing abnormal mucus will be a powerful tool,” said professor Steven M. Rowe, MD, director of the Gregory Fleming James Cystic Fibrosis Research Center, professor of medicine at the University of Alabama at Birmingham, and the other co-principal investigator of the study.
“Now we’ll be able to see how various treatments — not only those intended to fix the mucus, but also agents that repair the basic CF defect — affect airways,” Rowe added.
The team believes that the device might also be useful for other respiratory diseases.
“These results demonstrate the utility of μOCT [micro-optical coherence tomography] to determine epithelial function and monitor disease status of CF airways on a per-patient basis, with applicability for other diseases of mucus clearance,” the researchers said.