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: 8385542
• 负责人: Bastiaan Driehuys
• 金额: $ 36.88万
• 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/8385542
• 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.

描述（由申请人提供）：可以说是阻止治疗慢性肺部疾病进展的最大差距是缺乏评估肺功能的足够敏感，全面和无创的手段。在填补这一差距之前，患者将获得对他们不起作用的药物，而新疗法的开发将保持昂贵，缓慢且在很大程度上失败。因此，我们的研究的长期目标是开发和实施一种方法，以非侵入性和纵向形象形象心肺功能和结构的所有相关方面。我们的方法使用超极化（HP）129XE MRI来图像通风，微观结构和气体交换。该应用的目的是优化我们最近在人类受试者中通过129XE MRI进行图像区域气体交换的能力，使用优化的方法来测量和理解静息灌注异质性，并证明这种成像方法的灵敏度以检测变化的变化区域肺部功能要早得多。中心假设是，与可用均值相比，区域气体交换是肺功能早期变化的最敏感标记。拟议的研究的理由是，开发一种可以非侵入性评估区域气体交换的方法，可以通过提供更敏感和更具体的测量方法来大大加速肺部医学的研究。因此，拟议的研究与NIH任务的那部分有关，该研究与通过开发和加速生物医学技术的应用来改善健康有关。在强大的初步数据的指导下，将通过追求三个具体目的来测试中心假设：1）优化3D血液选择性129XE 129XE气体交换MRI 2）建立图像可重复性作为时间，姿势和心脏输出的函数，以及3）图像放射治疗期间区域气体交换的时间演化。与黄金标准相比，这些目标的完成将确定这种新方法的效用，敏感性和局限性，同时将其定位为肺部医学研究的敏感生物标志物。预计第一个目标将改善当前的气体交换图像分辨率8倍，增加纤维化的特异性，并建立管理收购的关键MR物理学。第二个目的将揭示在初步研究中已经观察到的129 XE气体交换的静息异质性的关键决定因素并确定其可重复性。最终目标将这些技术和发展见解汇集在一起​​，以检验以下假设：129XE MRI将比当前可用的手段更早检测天然气交换的变化。提出的方法具有创新性，因为它利用了HP 129XE MRI的独特性能以及创新的获取，以形象肺部最基本的功能 - 气体交换。拟议的研究很重要，因为预计开发的成像方法将为肺部微循环的长期转移提供一个长期的气体转移窗口。