Chen, Wong Win NIH Grant to Characterize Mucosal Health

Sep. 21, 2020 - UC Irvine biomedical engineering professor Zhongping Chen and otolaryngologist/facial surgeon Dr. Brian Wong recently won a $2.3 million, four-year R01 award from the NIH’s National Institute of Biomedical Imaging and Bioengineering to develop a technology that could help doctors treat sinus and nasal ailments with more precise information. The two, who have collaborated for nearly 20 years, are creating an innovative in vivo imaging system they call a phase-resolved spectrally encoded endoscope (PR-SEE).

Approximately 50 million Americans each year suffer from painful sinus and allergic nasal upper respiratory ailments. Known medically as chronic rhinosinusitis and allergic rhinitis, the resulting headaches, stuffy/runny noses, itchy, watery eyes and sneezing are responsible for health care expenditures of more than $35 billion a year, along with 3.5 million missed work days. “It’s a quality of life issue,” says Wong, who has a joint appointment in the Samueli School’s biomedical engineering department. “You’re probably not going to die from it; you’re just going to be miserable.”

Doctors are limited in their ability to treat these patients, relying mostly on subjective information gleaned from the patients themselves. “Right now, the response to therapy is entirely based on patient-reported outcomes,” says Wong, who adds that it’s difficult to develop appropriate therapies with these “semi-quantitative responses.”

The PR-SEE will employ two distinct imaging techniques that will overcome current limitations on in vivo cilia imaging. (Cilia are the tiny, hairlike structures on airway cell surfaces that sweep in a rhythmic pattern to transport mucus.) The first, optical coherence tomography (OCT), uses two scanning mirrors to provide information from deep within tissue; the second is spectrally encoded interferometry, a method that uses one mirror, providing faster imaging speed, but which cannot achieve deep measurements like OCT. Used together, the two techniques can give medical professionals quantitative information they have not had access to. “This has never been done in vivo before,” Chen says.

The device will measure ciliary beat frequency (CBF) – the speed at which the cilia sweep. Along with other factors, the CBF determines the efficiency of mucus transport, providing a strong indicator of upper airway health.

The device also will assess amplitude and propagation of the mucosal metachronal waves. “CBF is only one of the many factors that dictate the ability of cilia to transport mucus,” explains Chen. “It is also important to study the sweeping pattern (the amplitude) and how well each cilium coordinates with each other (the metachronal waves).

“These quantitative factors – speed/frequency, amplitude, metachronal waves – will provide a more comprehensive understanding of how airway cilia work, and will go a long way toward determining upper airway health,” he says.

In order to obtain functional parameters, Chen and Wong will test their device first on a rabbit nasal airway model, then on anaesthetized patients undergoing nasal surgeries. Eventually, they plan to develop stabilization techniques to help keep non-anaesthetized patients from moving in order to translate the research into a device that can be used in a doctor’s office.

Rhinosinusitis alone currently accounts for more antibiotic prescriptions than any other diagnosis in ambulatory settings, and in more severe cases, results in 600,000-plus sinonasal operations annually.  

“Last time I checked, there were over 400 medications approved by the FDA for use in treating the nose. This additional information will help in identifying proper therapies and in determining whether those therapies are working,” Wong says. “We need a rigorous means to measure the response to pharmacological therapy and/or surgery by probing mucosal physiology at a fundamental level.”

Adds Chen: “This imaging modality establishes an objective means to gauge sinus health and the response to treatment, which in turn will aid scientists, clinicians and industry professional to better develop drugs, devices and other therapies.”

– Anna Lynn Spitzer

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