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

项目总结 每年有5000万美国人患有慢性鼻窦炎(CRS)和过敏性鼻炎(AR)。这个 仅在医疗保健支出方面，经济影响就超过350亿美元/年，超过350万个工作岗位和200万个工作岗位 每年损失的在校天数。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，严重降低了生活质量，而且经常被忽视，因为 死亡率低，而发病率高。目前，使用患者报告的结果衡量标准来评估 CRS和AR中的疾病状态，因为没有可靠的量化方法来衡量疾病的严重性或 对治疗的反应。成败是由患者的主观报告决定的，或者通过 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 可以测量的是睫状体搏动频率(CBF)。纤毛控制粘液纤毛的运输，这是 鼻窦粘膜的终点生理功能。在临床环境中活体测量脑血流是具有挑战性的， 但在潜在监测粘膜健康和治疗反应方面有价值。 这项建议是对PAR-19-158 NIBIB生物工程研究补助金的回应，旨在 开发和验证一种创新的活体成像系统来测量脑血流量和相关的生理 表征粘膜健康状况的参数。陈博士和王博士已经连续合作了超过 在光学成像、系统和探头设计以及翻译这些台式计算机方面拥有20年的专业经验 将技术转化为临床应用。该方案以设计、施工和临床评估为中心。 相位分辨光谱编码内窥镜(PR-SEE)与光学相干层析成像的集成 (10月)。PR-SEE将能够对活体鼻黏膜进行功能成像，从而能够测量CBF 此外，它还可以显示整个鼻黏膜的图像，并便于分析纤毛搏动模式(CBP)。更多 重要的是，PR-SEE将提供一种严格的方法来评估 粘膜异染色质波(MWs)，这是粘液纤毛运输的可量化终点功能。 所提出的成像设备集中在包含光谱的同轴扫描方案上 编码干涉测量和OCT，以克服目前体内纤毛成像的限制。评估和 验证我们的设备，我们将首先在兔鼻气道模型上进行PR-SEE，然后进行成像 麻醉患者在手术室获取睫状体功能参数(CBF、CBP、MWs)。六十 接受鼻部手术(正常对照，如鼻中隔成形术)或鼻窦手术(CRS患者)的受试者将 被招募参加这项研究。在手术室成功的临床翻译将为PR-SEE成像做准备 在随后的研究中，在办公室唤醒患者。我们坚信，启用功能量化 粘膜健康将推动药物治疗、设备和外科干预的发展。

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.