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: 10055245
• 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/10055245
• 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 Airway Disease; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Contrast Media; Cross-Sectional Studies; Cystic Fibrosis; Data; Development; Disease; Effectiveness; Ensure; Feasibility Studies; Fluorine; Functional disorder; Gases; Goals; Grant; High Resolution Computed Tomography; Image; Infant; Infection; 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; Research Training; Respiratory Failure; Respiratory physiology; 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; cohort; cost; cystic fibrosis patients; healthy volunteer; indexing; informal learning; innovation; lung imaging; novel therapeutics; pediatric patients; preservation; prevent; public health relevance; structured data; 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