Xe129 MRI of the Lung: A New Technology to Assess Treatment for COPD

Xe129 肺部 MRI：评估 COPD 治疗的新技术

• 批准号: 8953629
• 负责人: Kun Qing
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-07 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8953629
• 关键词: Address; Advair; Alveolar; Blood; Blood gas; Breathing; Bronchodilator Agents; Carbon Monoxide; Cause of Death; Characteristics; Chest; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Clinical assessments; Data; Detection; Development; Diagnosis; Diagnostic; Diffuse; Disease; Environmental air flow; Evaluation; Exercise Tolerance; FDA approved; Foundations; Future; Gases; High Resolution Computed Tomography; Human; Image; Imaging Techniques; Individual; Inhalators; Investigation; Lobar; Lobe; Lung; Lung Capacity; Lung diseases; Magnetic Resonance Imaging; Mainstreaming; Maps; Measures; Medicine; Methods; Monitor; Outcome Measure; Pathologic; Pathologic Processes; Patients; Performance; Perfusion; Perfusion Weighted MRI; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Physiological; Pilot Projects; Process; Public Health; Pulmonary function tests; Quality of life; Research; Resolution; Respiratory physiology; Sensitivity and Specificity; Staging; Steroids; Structure of parenchyma of lung; Techniques; Testing; Therapeutic; Time; Tissues; United States; X-Ray Computed Tomography; Xenon; analog; base; clinically relevant; cost; density; disability; drug development; imaging modality; improved; lung lobe; new technology; non-invasive imaging; novel; novel therapeutics; public health relevance; response; tool; uptake

 DESCRIPTION (provided by applicant): COPD is the third leading cause of death in the US. Development of novel therapies for COPD is currently hampered by lack of clinical tools to assess therapeutic responses. Magnetic resonance imaging (MRI) using hyperpolarized xenon-129 (Xe129) gas has emerged as a candidate to address this need. Recently, our research group developed a new Xe129 MRI technique that permits 3D regional mapping of both ventilation (airflow) and gas uptake (gas exchange) by tissue and blood in the human lung through a single breath hold acquisition (<11 seconds). To our knowledge, it is the first non-invasive imaging method to measure regional gas exchange - the primary function of the human lung. Our preliminary studies showed a high potential of this technique to detect diverse functional and pathological changes in the lungs with COPD. So the primary objective of this application is to test the ability of Xe129 MRI as a diagnostic tool to detect a response to curren mainstream therapeutics for COPD, and compare it with performances of existing clinical tools. And the secondary objective is to use high resolution computed tomography (HRCT) and pulmonary perfusion MRI to verify the abnormalities of lung functions detected by Xe129 MRI (gas uptake by lung tissue and blood), and thus indirectly validate this technique. The central hypothesis is that Xe129 MRI enables detection of physiologically relevant and clinically important pathologic changes found in the lungs of COPD subjects with unprecedented sensitivity, specificity and 3D resolution, which are not obtainable by standard clinical methods, thus, can be used to promote rapid development of novel therapeutics to benefit patients diagnosed with COPD. Guided by strong preliminary data, the central hypothesis will be tested by pursuing two Specific Aims: 1). Implement an image post-processing method to co-register images from Xe129 MRI, perfusion MRI and HRCT acquisitions, and subdivide them to individual lung lobes; 2). Perform a pilot study in 30 COPD patients (10 in each of GOLD stages 1-3) starting a combined inhaler, Advair, for a 90-day trial to assess the functional responses in the COPD lungs to treatment using Xe129 MRI, and investigate the correlation between Xe129 MRI, perfusion MRI and HRCT. Achieving Aim 1 will lay the foundation for quantitative analysis of the regional lung function and investigation of the correlations between different imaging acquisitions in Aim 2. Aim 2 will test the central hypothesis that Xe129 MRI can detect potential diagnostic gains obtained by considering regional effects of Advair in lungs with COPD, which is not obtainable by using existing clinical tools, and also validate the Xe129 MRI technique. The results of the project are expected to improve our understanding of the functional response of the lungs with COPD to current therapeutics, and provide evidence to consider Xe129 MRI as a diagnostic strategy to assess and monitor therapeutic responses of existing and new pharmaceuticals, and thus this technique can stimulate development of novel therapies for COPD in the future.

 描述（由申请人证明）：y缺乏临床工具的临床工具。我们的研究小组为候选人​​提供了一个新的应用程序，该应用程序通过单一的呼吸获取，通过人类lungg中的组织和血液对烟气的吸收（气体交换）。 - 测量人类肺部的区域气体交换E的原始功能。对当前的COPD主流治疗方法的反应，并将其与现有临床工具的性能进行比较。中心假设是XE129 MRI可以在COPD的肺中检测生理学和临床上重要的病理学。 copd。每个阶段的1-3阶段）是为期90天的试验，以评估COPD肺部使用XE129 MRI治疗的功能，并研究XE129 MRI，灌注MRI和HRCT之间的相关性。为区域肺功能的定量分析奠定基础，并研究AIM 2 AIM 2中不同成像采集之间的相关性，将检验XE129 MRI可以通过考虑Advaine COPD的区域效应而获得的XE129 MRI可以脱口的假设，而不是ITH COPD的区域效应，这不是可通过使用临床工具获得，还可以验证XE129 MRI技术。药品和该技术可以激发未来COPD新型疗法的后期开发。