Imaging of Pulmonary Mucociliary Clearance

描述(由申请人提供)：这项建议的总体目标是优化用于研究囊性纤维化(CF)患者肺部呼吸道生理学的成像技术。粘膜纤毛清除(MCC)是一种主要的呼吸道宿主防御机制，它的缺陷使CF患者更容易受到慢性感染，并最终危及生命。进一步开发量化MCC和CF潜在病理生理学的成像技术将增加它们作为结果衡量标准的实用性，从而允许加速评估最终延长这一人群生存的治疗方法。该提案的研究部分包括开发一种2-同位素核医学扫描，以同时评估粘液纤毛清除率和呼吸道表面液体容量。这是研究人员以前用来研究这一人群MCC的单同位素技术的扩展。还将利用手动和自动定量计算机断层扫描(CT)技术，使清除率的区域差异与肺部内的特定病理相匹配，并定位于特定大小范围内的呼吸道。还提出了一种新系统的设计，以更精确、可重复和更有针对性地提供用于评估肺清除的气雾剂。获奖期间提出的职业发展包括：(1)持续的CF研究培训，(2)先进核医学技术的指导研究，(3)CT图像量化指导，(4)生物医学基础的研究生课程，(5)与北卡罗来纳大学从事类似研究兴趣的研究人员的持续咨询，(6)继续参加关于纤毛、粘液和粘液纤毛相互作用的戈登会议，以及(7)每月从胸科放射科医生那里学习CT扫描解释。拟议的研究和培训将提供必要的核心技能，以便在工程学和医学之间的独特界面领域实现研究独立。(摘要结束)

DESCRIPTION (provided by applicant): The general aim of this proposal is to optimize the imaging techniques used to study airway physiology in the lungs of patients with cystic fibrosis (CF). Deficiencies in mucociliary clearance (MCC), a primary airway host defense mechanism, make patients with CF more vulnerable to chronic and ultimately life threatening infections. Further development of the imaging techniques that quantify MCC and the underlying pathophysiology of CF will increase their utility as outcome measures, allowing for the accelerated evaluation of treatments that will ultimately extend the survival of this population. The research portion of the proposal includes the development of a 2-isotope nuclear medicine scan to simultaneously assess mucociliary clearance rate and airway surface liquid volume. This is an extension of the single isotope technique previously used by the investigators to study MCC in this population. Manual and automated quantitative computed tomography (CT) techniques will also be utilized, allowing regional differences in clearance rate to be matched to specific pathologies within the lungs and localized to airways within specific size ranges. The design of a new system for more precise, repeatable, and targeted delivery of the aerosols used to assess pulmonary clearance is also proposed. Career development proposed during the award includes: (1) on going research training in CF, (2) the mentored study of advanced nuclear medicine techniques, (3) instruction in CT image quantification, (4) a graduate course in the Foundations of Biomedical Science, (5) an on-going consultation with researchers at the University of North Carolina who are pursuing similar research interests, (6) continued participation in Gordon Conferences on cilia, mucus, and mucociliary interactions, and (7) monthly instruction from a thoracic radiologist to learn CT scan interpretation. The proposed research and training will provide the core skills necessary to progress towards research independence in a field at a unique interface between engineering and medicine. (End of Abstract)