In vivo Imaging and Quantification of Cilia Beating Dynamics Using Phase-Resolved Optical Imaging Technology

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PROJECT SUMMARY Each year, 50M Americans suffer from chronic rhinosinusitis (CRS) and allergic rhinitis (AR). The economic impact accounts for over $35B/year in health care expenditures alone, with over 3.5M work and 2M school days lost each year. Accordingly, over 600K operations per year are performed to treat sinonasal disease. The disease burden is immense with a profound reduction in quality of life, and is often overlooked because mortality is low, while morbidity is high. Currently, patient-reported outcome measures are used to evaluate disease status in CRS and AR, as there are no reliable quantitative methods to gauge disease severity or response to therapy. Success or failure is determined by the subjective reports from the patient alone, or via physician-directed endoscopy, where interpretation may also be subjective. One potential biophysical variable that can be measured is ciliary beat frequency (CBF). The cilia control mucociliary transport, which is the endpoint physiologic function of the sinonasal mucosa. CBF is challenging to measure in vivo in a clinical setting, but has value in potentially monitoring mucosal health and the response to therapy. This proposal is in response to the PAR-19-158 NIBIB Bioengineering Research Grants and aimed to develop and validate an innovative in vivo imaging system to measure CBF and the related physiological parameters that characterize mucosal health. Drs. Chen and Wong have had continuous collaborations for over 20 years with expertise in optical imaging, system, and probe designs, as well as translating these bench-top technologies to clinical applications. This proposal centers on the design, construction, and clinical evaluation of phase-resolved spectrally encoded endoscopy (PR-SEE) integrated with optical coherence tomography (OCT). PR-SEE will enable functional imaging of the nasal mucosa in vivo, allowing surveying the CBF landscape across the nasal mucosa as well as facilitating the analysis of ciliary beat pattern (CBP). More importantly, PR-SEE will provide a rigorous means to assess the speed, amplitude, and propagation of the mucosal metachronal waves (MWs), which are the quantifiable endpoint function of mucociliary transport. The proposed imaging device concentrates on a coaxial scanning scheme encompassing spectrally encoded interferometry and OCT to overcome the current limitations for in vivo cilia imaging. To evaluate and validate our device, we will first perform PR-SEE on a rabbit nasal airway model, followed by imaging of anesthetized patients in the operation room to obtain ciliary functional parameters (CBF, CBP, MWs). Sixty subjects undergoing nasal operations (normal control, e.g., septoplasty) or sinus surgeries (CRS patients) will be recruited for the study. Successful clinical translation in the operation room will prepare PR-SEE for imaging awake patients in the office in subsequent studies. We firmly believe that enabling functional quantification of mucosal health will jumpstart the developments in pharmacotherapy, devices, and surgical intervention.