Quantitation and Spatial Registration of Airways Dysfunction with Dynamic 19F MRI in Cystic Fibrosis

摘要 囊性纤维化患者动态~(19)F MRI对呼吸道功能障碍的定量和空间配准 基本原理：目前可用于在CF中测试新疗法的终点通常对焦点不敏感 肺部疾病和早期肺部疾病的变化(例如，肺活量测定)，或需要电离辐射(例如，胸部CT)。 这些问题限制了它们的用途，通常会阻止重复使用，特别是在幼儿中。加法 使用MRI将吸入气体作为造影剂在保留空间信息的同时量化通气量 技术是肺部成像的一个重要进步，但还没有广泛应用。我们建议开发 使用全氟化气体进行核磁共振成像，这可能比其他方法有几个重要的优点 技术，包括可随时转移到其他研究中心。方法：囊性纤维化受试者 除1H外，还将接受全氟丙烷(PFP)增强磁共振成像(19F MRI) 超短回波时间(UTE)磁共振成像。在纵向研究中，我们将评估短期变异性和 ~(19)F-MRI对疾病状态变化的反应性及其与功能变化的关系 在通风和肺结构方面。传统结果测量的平行测量(肺活量测定法、肺 清除指数和患者症状)将有助于评估以下各项是否增加了敏感性和价值 这项技术。受试者还将接受与肺恶化有关的测试，以确定 在不同生理状态下的表现。19F核磁共振将扩展到儿科年龄范围 确定在幼儿中进行这些研究的可行性，以及在儿童中检测疾病的能力 肺活量正常。培训：戈拉尔斯基博士将开始临床研究课题的专门培训 (高级研究设计和生物统计学)，以及医学成像分析方面的培训，以促进她的目标 成为一名独立的调查员。她还将在预科阶段寻求正规和非正规教育。 设计和生物统计学方法。预期结果：我们预计19F核磁共振能很容易地发现异常 在慢性肺病受试者的小气道功能方面，这些测量在短时间内是有效的， 它们将反映疾病活动的急剧变化(即病情恶化)。我们还预计19F核磁共振 在幼儿中是可行的，并将能够检测到通风不均匀，即使在年轻的CF受试者中也是如此 经常规方法(即肺活量测定)检测肺功能正常的患者。

ABSTRACT Quantitation and Spatial Registration of Airways Dysfunction with Dynamic 19F MRI in Cystic Fibrosis Rationale: Currently available endpoints for testing of new therapies in CF typically are either insensitive to focal changes in lung disease and early lung disease (e.g. spirometry), or require ionizing radiation (e.g. chest CT). These problems limit their utility, and typically prevent repetitive use, particularly in young children. The addition of an inhaled gas as a contrast agent to quantify ventilation while preserving spatial inforrmation using MRI techniques is an important advance in pulmonary imaging, but is not yet widely available. We propose to develop the use of a perfluorinated gas for MRI imaging, which may have several important advantages over other techniques, including being readily transferrable to other research centers. Methods: Subjects with cystic fibrosis will undergo perfluoropropane (PFP)-enhanced magnetic resonance imaging (19F MRI), in addition to 1H ultrashort echo time (UTE) MRI. In a longitudinal study, we will evaluate the short-term variability and responsiveness of 19F MRI to disease state changes while exploring the relationship between functional changes in ventilation and lung structure. Parallel measurement of traditional outcome measures (spirometry, lung clearance index, and patient symptoms) will help evaluate whether additional sensitivity and value is added by this technique. Subjects will be tested in relation to pulmonary exacerbations as well to determine measure performance over different physiologic states. 19F MRI will be extended down to the pediatric age range to determine the feasibility of performing these studies in young children, and the ability to detect disease in children with normal spirometry. Training: Dr. Goralski will embark upon specialized training in clinical research topics (advanced study design and biostatistics), as well as training in medical imaging analysis to further her goal in becoming an independent investigator. She will also seek both formal and informal education in advance study design and biostatistical methods. Expected Results: We expect that 19F MRI will readily detect abnormalities in small airway function in subjects with CF lung disease, that measurements will be valid over short time frames, and that they will reflect acute changes in disease activity (i.e. exacerbations). We further expect that 19F MRI will be feasible in young children and will be able to detect ventilation inhomogeneity, even in young CF subjects with normal lung function tested by conventional means (i.e. spirometry).