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: 9309935
• 负责人: Bastiaan Driehuys
• 金额: $ 46.31万
• 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 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309935
• 关键词: Address; Animal Model; Asthma; Biomedical Technology; Blood Vessels; Breathing; Characteristics; Chemicals; Chronic Obstructive Airway Disease; Clinical; Clinical Research; Comorbidity; Complex; Data; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Dyspnea; Early Diagnosis; Environmental air flow; Exhibits; Fibrosis; Frustration; Functional Imaging; Funding; Gases; Goals; Hamman-Rich syndrome; Health; Health Care Costs; Heart Diseases; Histology; Image; Impairment; Left; Letters; Link; Lung; Lung diseases; Magnetic Resonance Imaging; Maps; Measures; Methodology; Methods; Mission; Modeling; Monitor; Multicenter Studies; Noise; Obstruction; Obstructive Lung Diseases; Operative Surgical Procedures; Outcome; Pathology; Patients; Pattern; Phase; Phase III Clinical Trials; Phenotype; Physics; Positioning Attribute; Process; Productivity; Protocols documentation; Pulmonary Emphysema; Pulmonary Fibrosis; Pulmonary Gas Exchange; Pulmonary Hypertension; Pulmonary Pathology; Radiation; Radiation Injuries; Radiation therapy; Reproducibility; Research; Research Infrastructure; Respiratory physiology; Rodent Model; Solubility; Syndrome; Techniques; Technology; Testing; Three-Dimensional Imaging; Time; United States National Institutes of Health; Vascular Diseases; Work; Xenon; airway obstruction; base; clinical practice; cohort; cost efficient; design; disease phenotype; experience; frontier; functional disability; guided inquiry; healthy volunteer; human subject; imaging modality; improved; innovation; interstitial; lung imaging; lung injury; lung visualization; outcome prediction; phase III trial; pre-clinical; preclinical study; prevent; public health relevance; pulmonary function; reconstruction; spectroscopic imaging; tool; trend; vascular factor

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.

项目总结/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 美国每年的医疗费用为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 灵敏可靠的工具来诊断和表型疾病，并优化治疗。超极化129 xe 气体磁共振成像正在成为一种有前途的解决方案，用于肺功能的非侵入性3D成像-现在， 通气MRI的III期临床试验，正在研究将其扩展到肺部气体成像 交易所这一新的前沿提供了与肺气肿、间质性或 血管疾病过程。我们现在可以使用129 MRI来量化与这些相关的区域损伤， 条件但是，肺部病理很少表现为一种孤立的疾病;患者经常患有多种疾病， 疾病同时发生。我们打算通过全面的研究， 在人类受试者和动物模型中进行的研究不仅可以量化气体交换损伤，而且可以确定其 根本原因我们的长期目标是开发一种时间和成本效益高的非侵入性MRI检查， 量化肺气肿、间质性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开创临床前和临床129 μ M MR成像方面的独特经验， 以及气体交换的定量分析。本研究的目的是推进129年来的方法学 气体交换MRI采集和分析，同时进行临床前和临床研究， 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 一个全面的协议，包括交换成像和光谱，在动物模型，健康 志愿者和患者，疾病的关键特征将被识别。建议的理由 研究表明，更精确的诊断信息对于帮助临床医生准确及时地进行诊断至关重要。 治疗决定因此，这项工作与国家卫生研究院的使命有关，即通过以下措施改善健康状况： 发展和加速生物医学技术。在强有力的初步数据的指导下，我们的方法是 基于四个特定目标：1）129 mA气体交换（GX）MRI标测图的双SNR和CNR; 2）表征 在肺气肿、纤维化和肺动脉高压（PH）的啮齿动物模型中的GX MRI; 3）在肺气肿、纤维化和肺动脉高压（PH）的啮齿动物模型中定量GX MRI。 监测放疗前后GX MRI的变化。这些目标 将1）定位GX MRI用于多中心部署，2）在GX MRI功能之间建立明确的联系， 病理学，和3）识别肺气肿，间质性，和 血管疾病这种方法是创新的，因为它利用了独特的溶解度和化学位移， 129位和复杂的编码，以测量特征良好的动物模型和患者的特征， 一系列疾病这项研究意义重大，因为它推动我们走向一个单一的，非侵入性的 3D功能成像模式，可以在一次呼吸中表征和量化潜在的病理。