Early Detection of Changes in Pulmonary Gas Exchange by Hyperpolarized Xe MRI

通过超极化 Xe MRI 早期检测肺部气体交换的变化

• 批准号: 8214524
• 负责人: Bastiaan Driehuys
• 金额: $ 38.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214524
• 关键词: Aftercare; Alveolitis; Biological Markers; Biomedical Technology; Blood; Blood Vessels; Blood capillaries; Cancer Patient; Cardiac Output; Cardiopulmonary; Chest; Chronic; Chronic Disease; Clinical Research; Data; Development; Disease; Disease Progression; Dose; Early Diagnosis; Environmental air flow; Erythrocytes; Evolution; Exercise; Fibrosis; Force of Gravity; Functional Imaging; Gases; Goals; Gold; Health; Healthcare Systems; Heterogeneity; Human; Human Volunteers; Image; Imaging Techniques; Individual; Knowledge; Lung; Lung diseases; Magnetic Resonance Imaging; Measurement; Measures; Methods; Microcirculation; Mission; Monitor; Outcome; Patients; Perfusion; Pharmaceutical Preparations; Phase; Phenotype; Physics; Positioning Attribute; Posture; Property; Public Health; Pulmonary Gas Exchange; Pulmonary function tests; Pulmonology; Radiation; Radiation therapy; Reproducibility; Research; Resolution; Respiratory physiology; Rest; Scanning; Specificity; Staging; Structure; Testing; Therapeutic Intervention; Three-Dimensional Imaging; Time; Tissues; United States National Institutes of Health; Vision; Work; X-Ray Computed Tomography; base; capillary; clinically relevant; effective therapy; human subject; imaging modality; improved; innovation; insight; lung imaging; prevent; public health relevance; pulmonary function; single photon emission computed tomography; stem; tool; uptake

DESCRIPTION (provided by applicant): Arguably the biggest gap preventing progress in treating chronic pulmonary diseases is the lack of a sufficiently sensitive, comprehensive, and non-invasive means to evaluate lung function. Until this gap is filled, patients will receive medications that don't work for them, and development of new therapies will remain expensive, slow, and largely unsuccessful. The long-term goal of our research, therefore, is to develop and implement a means to image all relevant aspects of cardiopulmonary function and structure, non-invasively and longitudinally. Our approach uses hyperpolarized (HP) 129Xe MRI to image ventilation, microstructure, and gas exchange. The objective of this application is to optimize our recently demonstrated capability to image regional gas exchange by 129Xe MRI in human subjects, to use the optimized method to measure and understand resting perfusion heterogeneity, and to demonstrate the sensitivity of this imaging approach to detect changes regional lung function much earlier than currently possible. The central hypothesis is that regional gas exchange is the most sensitive marker of early changes in pulmonary function compared to available means. The rationale for the proposed research is that developing a method that can non-invasively evaluate regional gas exchange will dramatically accelerate research in pulmonary medicine by providing a more sensitive and specific measurement that can be used repeatedly. Thus, the proposed research is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating the application of biomedical technologies. Guided by strong preliminary data, the central hypothesis will be tested by pursuing three Specific Aims: 1) Optimize 3D blood-selective 129Xe gas exchange MRI 2) Establish image reproducibility as a function of time, posture, and cardiac output, and 3) Image the temporal evolution of regional gas exchange during radiation therapy. Completion of these aims will establish the utility, sensitivity and limitations of this new method compared to gold standards, while positioning it as a sensitive biomarker for research in pulmonary medicine. The first aim is expected to improve the current gas exchange image resolution 8-fold, add specificity for fibrosis, and establish the key MR physics governing the acquisition. The second aim will uncover the key determinants of the resting heterogeneity of 129Xe gas exchange already observed in preliminary studies and establish their reproducibility. The final aim brings these technical and developmental insights together to test the hypothesis that 129Xe MRI will detect alterations in gas exchange earlier than currently available means. The proposed approach is innovative because it exploits the unique properties of HP 129Xe MRI and an innovative acquisition to image lungs' most fundamental function - gas exchange. The proposed research is significant because the imaging method being developed is expected to provide a long-sought window on gas transfer into the pulmonary microcirculation as a harbinger of changing disease status. PUBLIC HEALTH RELEVANCE: The proposed studies will optimize and test a non-invasive imaging technique to evaluate the gas exchange in the lung on a regional basis. Such images could greatly enhance the sensitivity for detecting early lung disease and allow earlier determination of whether a particular therapy is improving a patient's lung function. The proposed research has relevance to public health because new tools for non-invasively evaluating lung function will not only improve patient outcomes, but will accelerate research to develop better therapies.

描述（由申请人提供）：可以说，阻碍慢性肺部疾病治疗进展的最大差距是缺乏足够敏感、全面和非侵入性的方法来评估肺功能。在这一缺口得到填补之前，患者将接受对他们不起作用的药物，而新疗法的开发将仍然昂贵、缓慢且基本上不成功。因此，我们研究的长期目标是开发和实施一种方法，以非侵入性和纵向方式对心肺功能和结构的所有相关方面进行成像。我们的方法使用超极化 (HP) 129Xe MRI 对通气、微观结构和气体交换进行成像。此应用的目的是优化我们最近展示的通过 129Xe MRI 对人体区域气体交换进行成像的能力，使用优化的方法来测量和了解静息灌注异质性，并证明这种成像方法检测区域变化的灵敏度肺功能恢复的时间比目前可能的时间要早​​得多。中心假设是，与现有手段相比，区域气体交换是肺功能早期变化最敏感的标志。拟议研究的基本原理是，开发一种可以非侵入性评估区域气体交换的方法，通过提供可重复使用的更灵敏、更具体的测量，将极大地加速肺医学的研究。因此，拟议的研究与 NIH 使命的一部分相关，即通过开发和加速生物医学技术的应用来改善健康。在强有力的初步数据的指导下，中心假设将通过追求三个具体目标进行检验：1) 优化 3D 血液选择性 129Xe 气体交换 MRI 2) 建立图像再现性作为时间、姿势和心输出量的函数，以及 3) 图像放射治疗期间局部气体交换的时间演变。完成这些目标将确定这种新方法与金标准相比的实用性、敏感性和局限性，同时将其定位为肺医学研究的敏感生物标志物。第一个目标预计将当前的气体交换图像分辨率提高 8 倍，增加纤维化的特异性，并建立控制采集的关键 MR 物理原理。第二个目标将揭示初步研究中观察到的 129Xe 气体交换静止不均匀性的关键决定因素，并确定其再现性。最终目标将这些技术和发展见解结合在一起，以检验 129Xe MRI 将比现有手段更早检测到气体交换变化的假设。所提出的方法具有创新性，因为它利用了 HP 129Xe MRI 的独特特性和创新性采集来对肺部最基本的功能（气体交换）进行成像。这项研究具有重要意义，因为正在开发的成像方法有望提供一个长期寻求的气体转移到肺部微循环的窗口，作为疾病状态变化的先兆。 公共健康相关性：拟议的研究将优化和测试非侵入性成像技术，以评估区域性肺部气体交换。此类图像可以极大地提高检测早期肺部疾病的灵敏度，并可以更早地确定特定疗法是否正在改善患者的肺功能。拟议的研究与公共卫生相关，因为非侵入性评估肺功能的新工具不仅会改善患者的治疗结果，而且会加速开发更好疗法的研究。