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: 10734829
• 负责人: Bastiaan Driehuys
• 金额: $ 76.51万
• 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 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734829
• 关键词: 3-Dimensional; Acceleration; Acute; Address; Affect; Aftercare; Alveolar; Anemia; Anticoagulation; Biological Markers; Biomedical Technology; Blood Component Removal; Blood Vessels; Blood capillaries; Blood donor; Blood flow; Carbon Monoxide; Cardiac; Cardiopulmonary; Caring; Chemicals; Chronic; Clinical assessments; Coagulation Process; Defect; Development; Diagnosis; Diagnostic tests; Diffuse; Diffusion; Disease; Disease Progression; Distal; Distress; Dizziness; Dyspnea; Early Diagnosis; Emergency Care; Emergency department visit; Erythrocytes; Etiology; Evaluation; Exercise Test; Exhibits; Gases; Goals; Health; Hemoglobin; Image; Interstitial Lung Diseases; Intervention; Long COVID; Lung; Lung diseases; Magnetic Resonance Imaging; Measurable; Measures; Membrane; Methods; Mission; Modeling; Multi-Institutional Clinical Trial; Neuromuscular Diseases; Operative Surgical Procedures; Outcome; Oxygen; Oxygen Therapy Care; Patients; Physiological; Population; Positioning Attribute; Prevalence; Pulmonary Embolism; Pulmonary Gas Exchange; Pulmonary Hypertension; Pulmonary function tests; Quality of life; Research; Research Personnel; Resources; Selection for Treatments; Shortness of Breath; Signal Transduction; Solubility; Symptoms; Techniques; Technology; Testing; Therapeutic; Therapeutic Trials; Time; Tissues; Transfusion; United States National Institutes of Health; Visualization; Work; X-Ray Computed Tomography; base; chronic pain; chronic thromboembolic pulmonary hypertension; clinical care; clinical decision-making; comparative; cost; deconditioning; experience; frailty; improved; innovation; insight; interstitial; lung hypoxia; lung imaging; medical attention; new technology; oxygen transport; patient population; public health relevance; pulmonary function; reconstruction; response biomarker; tool; trait; uptake; ventilation

Project Summary/Abstract Dyspnea (shortness of breath) is among the most common reasons for seeking medical attention. It has a prevalence rivaling chronic pain and accounts for 10% of emergency room visits. Dyspnea workups involve extensive diagnostic testing, with high cost, and a slow time to diagnosis. The burden of dyspnea will further increase as more patients present with symptoms from long COVID. 129Xe MRI provides a promising solution with its comprehensive, non-invasive, and rapid imaging of lung function. Enabled by its solubility and tissue- dependent chemical shift, 129Xe probes diffusive transfer from the distal airspaces through the pulmonary interstitium (membrane) to the capillary red blood cells (RBCs); this provides a 3D decomposition of the drivers of gas exchange. However, to fully evaluate dyspnea, we must address pulmonary hypertension (PH) and hypoxia. We do this by quantifying cardiogenic RBC signal oscillations, which can differentiate pre- and post- capillary PH and exploiting the 129Xe-RBC chemical shift to interrogate mean capillary blood oxygenation. But to incorporate these powerful 129Xe-RBC biomarkers, we must know how they are affected hemoglobin, changing alveolar oxygen tension and how they respond to changes in pulmonary vascular flow. Our long-term goal is to develop a 5-min, comprehensive, 129Xe MRI/MRS exam that reveals all the treatable traits of dyspnea. We bring a track-record of pioneering studies, advanced acquisition, reconstruction and analysis methods, and experienced clinician co-investigators who can access the necessary patient populations and comparative clinical assessments. The objective of this renewal is to demonstrate interventions that change each of the three 129Xe-RBC related biomarkers – RBC transfer, cardiogenic oscillations, and chemical shift. Our central hypothesis is that by employing appropriate patient populations and carefully selected interventions, each of these 129Xe-RBC markers can be modified in a way that solidifies our understanding of them for clinical decision making. The rationale for the proposed research is to advance these biomarkers into multi-center clinical trials to expand upon anticipated FDA approval for 129Xe ventilation MRI. This work is relevant to the NIH Mission of improving health by developing and accelerating the application of biomedical technologies. We will pursue three Specific Aims: 1) Establish and validate a hemoglobin correction for 129Xe MRI, 2) determine the effect of oxygen administration on 129Xe MRI/MRS Metrics, and 3) measure longitudinal therapeutic change in acute and chronic pulmonary embolism. Completion of these aims will 1) establish understanding of the RBC-associated 129Xe biomarkers, 2) how they respond to therapy, and 3) set the stage for broader studies of O2 therapy. The proposed approach is innovative because it uses novel technologies, patient groups and interventions to uncover the physiological drivers of dyspnea. It is significant because it will enable development of a single 5-minute 129Xe MRI/MRS exam that can efficiently assess the multiple possible etiologies of breathlessness.

项目概要/摘要 呼吸困难（呼吸短促）是就医的最常见原因之一。它有一个 其患病率与慢性疼痛相当，占急诊室就诊人数的 10%。呼吸困难检查涉及 广泛的诊断测试，成本高，诊断时间慢。呼吸困难的负担将进一步加重 随着越来越多的患者出现长期新冠肺炎症状，这种情况也会增加。 129Xe MRI 提供了一个有前途的解决方案 凭借其全面、无创、快速的肺功能成像。通过其溶解度和组织实现- 依赖化学位移，129Xe 探测从远端空腔通过肺部的扩散转移 间质（膜）到毛细血管红细胞（RBC）；这提供了驱动程序的 3D 分解 的气体交换。然而，为了全面评估呼吸困难，我们必须解决肺动脉高压（PH）和 缺氧。我们通过量化心源性红细胞信号振荡来做到这一点，这可以区分治疗前和治疗后 毛细血管 PH 值并利用 129Xe-RBC 化学位移来询问平均毛细血管血氧合。但要 结合这些强大的 129Xe-RBC 生物标志物，我们必须知道它们如何影响血红蛋白，改变 肺泡氧张力及其对肺血管流量变化的反应。我们的长期目标是 制定 5 分钟综合 129Xe MRI/MRS 检查，揭示呼吸困难的所有可治疗特征。我们带来 开创性研究、先进采集、重建和分析方法的记录，以及 经验丰富的临床医生联合研究者，可以接触必要的患者群体并进行比较 临床评估。此次更新的目的是展示可以改变这三个方面的干预措施 129Xe-RBC 相关生物标志物 – 红细胞转移、心源性振荡和化学位移。我们的中央 假设是，通过采用适当的患者群体和精心选择的干预措施，每个 这些 129Xe-RBC 标记物可以通过某种方式进行修改，以巩固我们对它们的理解以进行临床决策 制作。拟议研究的基本原理是将这些生物标志物推进多中心临床试验 扩展预期 FDA 批准的 129Xe 通气 MRI。这项工作与 NIH 的使命相关 通过开发和加速生物医学技术的应用来改善健康。我们将追求三个 具体目标：1) 建立并验证 129Xe MRI 的血红蛋白校正，2) 确定氧气的影响 129Xe MRI/MRS 指标的管理，以及 3) 测量急性和慢性的纵向治疗变化 肺栓塞。完成这些目标将 1) 建立对 RBC 相关 129Xe 的理解 生物标志物，2）它们对治疗的反应如何，3）为更广泛的 O2 疗法研究奠定了基础。拟议的 该方法具有创新性，因为它使用新技术、患者群体和干预措施来揭示 呼吸困难的生理驱动因素。这很重要，因为它将能够开发单个 5 分钟 129Xe MRI/MRS 检查可以有效评估呼吸困难的多种可能病因。

项目成果

Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension.

定量 129Xe MRI 可检测肺动脉高压大鼠模型中气体交换的早期损伤。

• DOI: 10.1038/s41598-020-64361-1
• 发表时间: 2020
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Virgincar,RohanS;Nouls,JohnC;Wang,Ziyi;Degan,Simone;Qi,Yi;Xiong,Xinyu;Rajagopal,Sudarshan;Driehuys,Bastiaan
• 通讯作者: Driehuys,Bastiaan

Pulmonary functional MRI: Detecting the structure-function pathologies that drive asthma symptoms and quality of life.

• DOI: 10.1111/resp.14197
• 发表时间: 2022-02
• 期刊: RESPIROLOGY
• 影响因子: 6.9
• 作者: Kooner, Harkiran K.;McIntosh, Marrissa J.;Desaigoudar, Vedanth;Rayment, Jonathan H.;Eddy, Rachel L.;Driehuys, Bastiaan;Parraga, Grace
• 通讯作者: Parraga, Grace

Enabling hyperpolarized (129) Xe MR spectroscopy and imaging of pulmonary gas transfer to the red blood cells in transgenic mice expressing human hemoglobin.

• DOI: 10.1002/mrm.24915
• 发表时间: 2013-11
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Freeman, Matthew S.;Cleveland, Zackary I.;Qi, Yi;Driehuys, Bastiaan
• 通讯作者: Driehuys, Bastiaan

Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI.

• DOI: 10.1016/j.mri.2015.04.005
• 发表时间: 2015-09
• 期刊: MAGNETIC RESONANCE IMAGING
• 影响因子: 2.5
• 作者: He, Mu;Robertson, Scott H.;Kaushik, S. Sivaram;Freeman, Matthew S.;Virgincar, Rohan S.;Davies, John;Stiles, Jane;Foster, William M.;McAdams, H. Page;Driehuys, Bastiaan
• 通讯作者: Driehuys, Bastiaan