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

• 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
• 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

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.

项目摘要 每年，有5000万美国人患有慢性鼻鼻炎（CRS）和过敏性鼻炎（AR）。这 仅在医疗保健支出中，经济影响占35B美元以上，工作量超过350万和2M 每年的上学日子。因此，每年进行超过600K的手术以治疗鼻窦疾病。 这种疾病负担巨大，生活质量大幅降低，并且经常被忽视，因为 死亡率很低，而发病率很高。目前，使用患者报告的结果指标用于评估 CRS和AR中的疾病状况，因为没有可靠的定量方法来衡量疾病严重程度或 对治疗的反应。成功或失败是由患者或通过的主观报告确定的 医师定向内窥镜检查，解释也可能是主观的。一个潜在的生物物理变量 可以测量的是睫状节拍频率（CBF）。纤毛控制的粘毛转运，这是 鼻窦粘膜的终点生理功能。 CBF在临床环境中测量体内的挑战， 但是在潜在监测粘膜健康和对治疗的反应方面具有价值。 该提案是对尼比布生物工程研究补助的尼比布（Nibib 开发和验证一种创新的体内成像系统，以测量CBF和相关的生理 特征粘膜健康的参数。博士。 Chen和Wong持续合作 具有光学成像，系统和探针设计方面的专业知识20年，并翻译了这些台面 临床应用的技术。该提案以设计，构建和临床评估为中心 与光学相干断层扫描集成的相分辨频谱编码的内窥镜检查（PR-SEEE） （OCT）。 pr-Seee将启用体内鼻粘膜的功能成像，允许对CBF进行测量 横跨鼻粘膜的景观以及促进睫状节模式（CBP）的分析。更多的 重要的是，Pr-Seee将提供一种严格的手段来评估速度，振幅和传播 粘膜下波（MWS），这是粘毛转运的可量化端点功能。 所提出的成像装置集中在同轴扫描方案上，包括光谱 编码的干涉法和OCT克服了体内纤毛成像的当前局限性。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-SESE，然后成像 手术室中的麻醉患者获得睫状功能参数（CBF，CBP，MWS）。六十 接受鼻操作（例如，隔膜成形术）或鼻窦手术（CRS患者）的受试者将 被招募进行研究。在操作室成功的临床翻译将准备成像的PR-SESE 随后的研究中的办公室中清醒患者。我们坚信，实现功能量化 粘膜健康将在药物治疗，设备和手术干预措施中开始发展。