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（由适用提供）：COPD是美国第三大死亡原因。目前，由于缺乏评估治疗反应的临床工具而开发了新型COPD疗法。使用超极化XENON-129（XE129）气体的磁共振成像（MRI）已成为解决此需求的候选者。最近，我们的研究小组开发了一种新的XE129 MRI技术，该技术允许通过单个呼吸获取（<11秒）在人类肺中通过组织和血液对通风（气流）和气体吸收（气体交换）的3D区域映射（<11秒）。据我们所知，这是测量区域气体交换的第一种非侵入性成像方法 - 人类肺的主要功能。我们的初步研究表明，通过COPD检测肺中的潜水功能和病理变化的技术可能很高。因此，本应用的主要目的是测试XE129 MRI作为检测对CURREN主流治疗COPD的反应的诊断工具的能力，并将其与现有临床工具的性能进行比较。次要目标是使用高分辨率计算机断层扫描（HRCT）和肺灌注MRI来验证XE129 MRI（肺组织和血液吸收的气体吸收）检测到的肺功能异常，从而间接验证了这项技术。假设是，XE129 MRI能够检测出具有前所未有的敏感性，特异性和3D分辨率的COPD受试者肺中与物理相关和临床上重要的病理变化，因此不能通过标准临床方法获得，因此可以使用这些方法来促进诊断为COPD诊断的新型患者的快速疗法。在强大的初步数据的指导下，将通过追求两个具体目标来检验中心假设：1）。实施一种图像后处理方法，以从XE129 MRI，灌注MRI和HRCT获取中共同注册图像，并将其细分为单个肺部爱。 2）。对30名COPD患者进行试验研究（在1-3阶段的每个阶段中，有10例）开始了一项合并吸入器Advair进行90天的试验，以评估COPD肺对使用XE129 MRI治疗的功能反应，并研究XE129 MRI，灌注MRI和HRCT之间的相关性。实现目标1将奠定对区域肺功能的定量分析和目标2中不同成像获取之间的相关性的投资。AIM2将检验XE129 MRI可以通过使用COPCD在肺中使用copd的区域效应来检测XE129 MRI可以通过使用现有临床工具和MR MR进行的XEE XEN的区域效应来检测潜在的诊断收益。预计该项目的结果将提高我们对COPD肺对当前治疗剂的功能反应的理解，并提供证据，以考虑XE129 MRI作为一种诊断策略，以评估和监测现有药物和新药物的治疗反应，因此，这项技术可以刺激将来COPD的新疗法开发。