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

项目摘要 每年有5000万美国人患有慢性鼻窦炎（CRS）和过敏性鼻炎（AR）。的 经济影响仅在医疗保健支出方面就占每年350亿美元以上，有超过350万人工作，200万人失业， 学校每年都在流失。因此，每年进行超过60万次手术来治疗鼻窦疾病。 疾病负担是巨大的，生活质量严重下降，但往往被忽视，因为 死亡率低，而发病率高。目前，患者报告的结局指标用于评估 CRS和AR的疾病状态，因为没有可靠的定量方法来衡量疾病严重程度， 对治疗的反应。成功或失败仅由患者的主观报告确定，或通过 医生指导的内窥镜检查，其中解释也可能是主观的。一个潜在的生物物理变量 可以测量的是纤毛搏动频率（CBF）。纤毛控制粘膜纤毛的运输，这是 鼻窦粘膜的终点生理功能。CBF在临床环境中体内测量具有挑战性， 但在潜在地监测粘膜健康和对治疗的反应方面具有价值。 本提案是对PAR-19-158 NIBIB生物工程研究赠款的回应，旨在 开发并验证创新的体内成像系统，以测量CBF和相关的生理 表征粘膜健康的参数。陈博士和黄博士已经有了持续的合作超过 在光学成像、系统和探头设计方面拥有20年的专业知识，并将这些台式 技术应用于临床。该提案集中在设计，施工和临床评价 相位分辨光谱编码内窥镜（PR-SEE）与光学相干断层扫描相结合 （OCT）。PR-SEE将能够在体内对鼻粘膜进行功能成像，从而可以测量CBF 跨鼻粘膜的景观以及促进纤毛搏动模式（CBP）的分析。更 重要的是，PR-SEE将提供一种严格的手段来评估速度、幅度和传播。 粘膜异时波（MW），其是粘膜纤毛运输的可量化的终点功能。 所提出的成像设备集中于同轴扫描方案， 编码干涉测量和OCT，以克服目前的限制，在体内纤毛成像。评价和 为了验证我们的设备，我们将首先在兔鼻气道模型上进行PR-SEE，然后对 手术室麻醉患者，获取睫状体功能参数（CBF、CBP、MWs）。六十 接受鼻手术的受试者（正常对照，例如，鼻中隔成形术）或鼻窦手术（CRS患者）将 被招募参加研究。手术室中成功的临床翻译将为成像准备PR-SEE 在随后的研究中唤醒办公室里的病人。我们坚信，使功能量化 粘膜健康将推动药物治疗、器械和外科手术的发展。

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.