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

 描述(申请人提供)：慢性阻塞性肺病是美国第三大死因。目前，由于缺乏评估治疗反应的临床工具，COPD新疗法的开发受到阻碍。使用超极化氙气-129(Xe129)气体的磁共振成像(MRI)已经成为解决这一需求的候选方法。最近，我们的研究小组开发了一种新的Xe129磁共振技术，通过一次屏气采集(11秒)，可以对人体肺部组织和血液的通风(气流)和气体吸收(气体交换)进行3D区域标测。据我们所知，这是第一种非侵入性成像方法来测量区域气体交换-人类肺的主要功能。我们的初步研究表明，这项技术在检测COPD患者肺部不同的功能和病理变化方面具有很高的潜力。因此，本应用程序的主要目标是测试Xe129 MRI作为诊断工具检测当前主流疗法对COPD的反应的能力，并将其与现有临床工具的性能进行比较。次要目的是使用高分辨率CT(HRCT)和肺灌注MRI来验证Xe129MRI检测到的肺功能异常(肺组织和血液的气体摄取)，从而间接验证这项技术。中心假设是，Xe129磁共振成像能够以前所未有的灵敏度、特异性和3D分辨率检测在COPD患者的肺部发现的生理相关和临床重要的病理变化，这些是标准临床方法无法获得的，因此，可以用于促进新疗法的快速发展，使诊断为COPD的患者受益。在强劲的初步数据的指导下，中心假设将通过追求两个具体目标来检验：1)。实现了一种图像后处理方法，将Xe129MRI、灌注MRI和HRCT采集的图像进行联合配准，并将其细分到各个肺叶；对30名COPD患者(GOLD分期1-3各10名)进行先导性研究，开始使用联合吸入器Advair，进行为期90天的试验，以评估COPD肺对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将为定量分析区域肺功能和研究AIM 2中不同成像采集之间的相关性奠定基础。目标2将检验中心假设，即Xe129 MRI可以检测到通过考虑Advair对COPD肺部的区域影响而获得的潜在诊断收益，这是现有临床工具无法获得的，并验证了Xe129 MRI技术。该项目的结果有望提高我们对COPD患者肺部对当前治疗方法的功能反应的理解，并为将Xe129 MRI作为一种诊断策略来评估和监测现有药物和新药物的治疗反应提供证据，从而促进未来COPD新疗法的开发。

 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.