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

项目摘要/摘要 涉及阻塞性、间质性和血管病变的肺部疾病占180美元以上 美国每年的医疗成本为10亿美元。阻碍这一趋势逆转的一个主要瓶颈是缺乏足够的 灵敏可靠的工具，用于诊断疾病和表型疾病，并优化治疗。超极化129Xe 气体磁共振成像正在成为肺功能的无创3D成像的一种有前途的解决方案-现在 呼吸机MRI的第三阶段临床试验，正在研究将其扩展到肺气体成像 交换。这一新的前沿提供了与肺气肿、间质或 血管疾病的过程。我们现在可以使用129Xe磁共振来量化与这些相关的区域损害 条件。但是，肺部病理很少表现为一种孤立的情况；患者经常遭受多个 疾病同时发生。我们打算通过全面的 在人类受试者和动物模型中进行的研究不仅量化了气体交换损害，而且确定了其 根本原因。我们的长期目标是开发一种既省时又省钱的非侵入性磁共振检查 量化肺气肿、间质和血管性肺功能损害的相对负担。 我们的方法利用了我们在临床前和临床129Xe磁共振成像方面的独特经验， 以及气体交换的定量分析。本研究目的是推进~(129)Xe的方法学研究 气体交换磁共振成像采集和分析，同时进行所需的临床前和临床研究 识别潜在病理的独特特征。我们的中心假设是，通过部署和优化 一种全面的方案，包括交换成像和光谱，在动物模型中，健康 志愿者和患者，疾病的关键特征将被识别出来。建议的理由是 研究表明，更准确的诊断信息对于帮助临床医生准确和及时地做出 治疗决定。因此，这项工作与NIH任务中与通过以下方式改善健康有关的部分相关 发展和加快生物医药技术。在强劲的初步数据指导下，我们的方法是 基于四个具体目标：1)用于129Xe气体交换(GX)磁共振图的双重SNR和CNR；2)表征 GX MRI在肺气肿、纤维化和肺动脉高压(PH)啮齿动物模型中的应用；3)GX MRI在 4)监测放射治疗前后GX-MRI的变化。这些目标 将1)定位用于多中心部署的GX MRI，2)在GX MRI功能和 病理，以及3)确定肺气肿、间质和肺组织的特征光谱和图像模式。 血管疾病。这种方法具有创新性，因为它利用了水的独特的溶解性和化学位移 129Xe和复杂的编码，用于测量具有良好特性的动物模型和患者的特征 疾病的广谱。这项研究意义重大，因为它推动我们走向一种单一的、非侵入性的 3D功能成像设备，可以在一次呼吸中表征和量化潜在的病理。

Project Summary/Abstract Pulmonary diseases involving obstructive, interstitial, and vascular pathologies account for more than $180 billion annual U.S. healthcare costs. A major bottleneck preventing reversal of this trend is lack of sufficiently sensitive and reliable tools to diagnose and phenotype disease, and optimize treatment. Hyperpolarized 129Xe gas MRI is emerging as a promising solution for non-invasive 3D imaging of pulmonary function—now in Phase III clinical trials for ventilation MRI, with research underway to extend it to image pulmonary gas exchange. This new frontier offers sensitivity to pathology associated with emphysematous, interstitial, or vascular disease processes. We can now use 129Xe MRI to quantify regional impairment related to these conditions. But, lung pathology rarely presents as one isolated condition; patients frequently suffer multiple disease processes simultaneously. We intend to disentangle these phenomena through comprehensive studies in human subjects and animal models to not only quantify gas-exchange impairment, but identify its underlying cause. Our long-term goal is to develop a time- and cost-efficient, non-invasive MRI exam to quantify the relative burdens of emphysematous, interstitial, and vascular pulmonary functional impairment. Our approach exploits our unique experiences in pioneering both preclinical and clinical 129Xe MR imaging, as well as quantitative analysis of gas exchange. The objective of this study is to advance methodology for 129Xe gas exchange MRI acquisition and analysis, while conducting the preclinical and clinical studies needed to identify unique signatures of underlying pathologies. Our central hypothesis is that by deploying and optimizing a comprehensive protocol that includes exchange imaging and spectroscopy, in animal models, healthy volunteers, and patients, the key signatures of disease will be identified. The rationale for the proposed research is that more precise diagnostic information is critical to help clinicians make accurate and timely therapy decisions. Thus, the work is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating biomedical technologies. Guided by strong preliminary data, our approach is based on four Specific Aims: 1) Double SNR and CNR for 129Xe gas exchange (GX) MRI maps; 2) Characterize GX MRI in rodent models of emphysema, fibrosis, and pulmonary hypertension (PH); 3) Quantify GX MRI in patients with COPD and PH; and 4) Monitor GX MRI changes before and after radiation therapy. These aims will 1) position GX MRI for multi-center deployment, 2) establish a clear link between GX MRI features and pathology, and 3) identify characteristic spectroscopic and image patterns in emphysematous, interstitial, and vascular disease. The approach is innovative because it exploits the unique solubility and chemical shift of 129Xe and sophisticated encoding to measure features in well-characterized animal models and patients across a broad spectrum of diseases. The research is significant because it drives us towards a single, non-invasive 3D functional imaging modality that can characterize and quantify underlying pathology in a single breath.