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

囊性纤维化中动态 19F MRI 气道功能障碍的定量和空间配准

• 批准号: 10688254
• 负责人: Jennifer L Goralski
• 金额: $ 20.1万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688254
• 关键词: 17 year old; Acute; Address; Adolescent; Adopted; Adult; Adverse effects; Age; Air; Airway Disease; Alveolar; Anesthetics; Asthma; Biochemical; Biological; Biological Markers; Biometry; Biostatistical Methods; Blood; Blood capillaries; Breathing; Bronchiectasis; Child; Childhood; Chronic; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Contrast Media; Cross-Sectional Studies; Cystic Fibrosis; Data; Development; Disease; Early Diagnosis; Ensure; Feasibility Studies; Fluorine; Functional disorder; Gases; Goals; Grant; High Resolution Computed Tomography; Image; Infant; Inhalation; Ionizing radiation; Life; Longitudinal Studies; Lung; Lung Transplantation; Lung diseases; Magnetic Resonance Imaging; Measurement; Measures; Medical; Medical Imaging; Methods; Mucous body substance; Nitrogen; Outcome; Outcome Measure; Oxygen; Patients; Performance; Pharmaceutical Preparations; Physiological; Population; Protons; Pulmonary Cystic Fibrosis; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Quality of life; Questionnaires; Radiation exposure; Reporting; Research; Research Design; Research Personnel; Respiratory Failure; Respiratory Tract Infections; Risk; Sedation procedure; Site; Solubility; Spirometry; Structure; Symptoms; Techniques; Technology; Testing; Time; Training; Vulnerable Populations; absorption; advanced disease; airway inflammation; chest computed tomography; children with cystic fibrosis; clinical outcome measures; cohort; cost; cystic fibrosis patients; effectiveness evaluation; healthy volunteer; indexing; informal learning; innovation; lung imaging; novel therapeutics; pediatric patients; preservation; prevent; public health relevance; pulmonary function; training opportunity; treatment response; triplet state; ventilation

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).

摘要 囊性纤维化气道功能障碍的动态19F MRI定量和空间配准 依据：目前用于CF新疗法测试的可用终点通常对局灶性不敏感 肺部疾病和早期肺部疾病的变化（例如肺功能测定），或需要电离辐射（例如胸部CT）。 这些问题限制了它们的实用性，并且通常防止重复使用，特别是在幼儿中。添加 作为对比剂的吸入气体，以量化通气，同时使用MRI保留空间信息 技术是肺部成像的重要进步，但尚未广泛使用。我们建议发展 使用全氟化气体进行MRI成像，这可能比其他方法具有几个重要的优点。 技术，包括易于转移到其他研究中心。方法：囊性纤维化患者 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）MRI。在纵向研究中，我们将评估短期变异性， 19F MRI对疾病状态变化的反应性，同时探索功能变化之间的关系 通气和肺结构。平行测量传统的结局指标（肺功能测定、肺 清除指数和患者症状）将有助于评估是否增加额外的敏感性和价值， 这种技术。还将检测受试者的肺部急性加重，以确定测量 不同生理状态下的性能。19F MRI将扩展至儿科年龄范围， 确定在幼儿中进行这些研究的可行性，以及检测儿童疾病的能力 肺量测定正常培训：Goralski博士将接受临床研究主题的专业培训 （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，以进一步实现她的目标， 成为独立调查员。她还将寻求正规和非正规教育的预先研究 设计和生物统计学方法。预期结果：我们预计19F MRI将很容易检测到异常 在患有CF肺病受试者的小气道功能中，测量将在较短的时间范围内有效， 并且它们将反映疾病活动的急性变化（即恶化）。我们进一步预计， 将在幼儿中可行，并能够检测通气不均匀性，即使在年轻的CF受试者中也是如此 通过常规方法（即肺活量测定法）测试肺功能正常。