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

使用相位分辨光学成像技术对纤毛跳动动力学进行体内成像和量化

基本信息

批准号：
10033635
负责人：
ZHONGPING CHEN
金额：
$ 59.36万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10033635
关键词：
3-Dimensional Absenteeism Adult Allergic rhinitis American Antibiotics Asthma Biomedical Engineering Biophysics Blood Pressure Catheters Child Chronic Obstructive Airway Disease Cilia Clinical Collaborations Congestive Heart Failure Cystic Fibrosis Data Development Device or Instrument Development Devices Diagnosis Discipline Disease Drug Delivery Systems Drug Monitoring Drug usage Endoscopes Endoscopy Excision Failure Frequencies Functional Imaging Functional disorder General Anesthesia Health Health Expenditures Heart Rate Human Image Imaging Device Imaging technology In Vitro Industry Inflammatory Interferometry Investigation Knowledge Lasers Light Link Maps Measurement Measures Medical Methods Microscope Modeling Monitor Morbidity - disease rate Morphologic artifacts Motion Mucociliary Clearance Mucous Membrane National Institute of Biomedical Imaging and Bioengineering Noise Nose Operative Surgical Procedures Optical Coherence Tomography Optics Oryctolagus cuniculus Outcome Measure Parkinson Disease Patient Outcomes Assessments Patients Pattern Performance Performance at work Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacotherapy Phase Physicians Physiological Physiology Pilot Projects Population Prevalence Primary Ciliary Dyskinesias Property Publishing Quality of life Reporting Research Research Project Grants Resolution Respiration Disorders Respiratory Mucosa Scanning Scheme Schools Scientist Series Severity of illness Sinus Site Source Speed Standardization Structure Structure of mucous membrane of nose Surface Surveys Swab System Technology Temperature Testing Therapeutic Time Tissue Sample Tissue imaging Tissues Translating United States Visual Visualization Work allergic airway disease awake base body system burden of illness chronic back pain chronic rhinosinusitis clinical application clinical translation cost design design and construction drug development economic cost economic impact experience human subject imaging modality imaging system in vivo in vivo imaging in vivo imaging system innovation minimally invasive mortality operation optical imaging recruit research clinical testing response rhinosinusitis success treatment response virtual

项目摘要

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.

项目概要每年有 5000 万美国人患有慢性鼻窦炎 (CRS) 和过敏性鼻炎 (AR)。这经济影响仅在医疗保健支出中就占每年超过 35B 美元，涉及超过 350 万个工作和 200 万个工作岗位每年都失去上学时间。因此，每年进行超过 60 万例手术来治疗鼻窦疾病。疾病负担巨大，生活质量严重下降，但常常被忽视，因为死亡率低，而发病率高。目前，患者报告的结果测量用于评估 CRS 和 AR 中的疾病状态，因为没有可靠的定量方法来衡量疾病的严重程度或对治疗的反应。成功或失败取决于患者的主观报告，或者通过医生指导的内窥镜检查，其解释也可能是主观的。一种潜在的生物物理变量可以测量的是纤毛跳动频率（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。 CBF 在临床环境中进行体内测量具有挑战性，但在监测粘膜健康和治疗反应方面具有潜在价值。该提案是对 PAR-19-158 NIBIB 生物工程研究补助金的回应，旨在开发并验证创新的体内成像系统来测量 CBF 和相关的生理学表征粘膜健康的参数。博士。陈和黄已经持续合作超过 20 年在光学成像、系统和探头设计以及转化这些台式技术方面拥有丰富的专业知识技术到临床应用。该提案以设计、施工和临床评估为中心相位分辨光谱编码内窥镜 (PR-SEE) 与光学相干断层扫描集成（十月）。 PR-SEE 将能够对体内鼻粘膜进行功能成像，从而能够测量 CBF 整个鼻粘膜的景观以及促进纤毛跳动模式（CBP）的分析。更多的重要的是，PR-SEE 将提供严格的方法来评估速度、幅度和传播粘膜异时波（MW），是粘膜纤毛运输的可量化终点函数。所提出的成像设备集中于包含光谱的同轴扫描方案编码干涉测量和 OCT 克服了目前体内纤毛成像的局限性。评估和为了验证我们的设备，我们将首先在兔子鼻气道模型上执行 PR-SEE，然后进行成像在手术室麻醉患者以获得纤毛功能参数（CBF、CBP、MWs）。六十接受鼻部手术（正常对照，例如鼻中隔成形术）或鼻窦手术（CRS 患者）的受试者将被招募参加该研究。手术室成功的临床转化将为 PR-SEE 成像做好准备在随后的研究中，办公室里的病人是清醒的。我们坚信，实现功能量化粘膜健康将推动药物治疗、设备和外科手术的发展。