Imaging of pulmonary arterial hypertension with proton MRI

质子 MRI 肺动脉高压成像

• 批准号: 10704305
• 负责人: Susan R Hopkins
• 金额: $ 68.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10704305
• 关键词: Affect; Age; Biological Markers; Blood Vessels; Blood flow; Breathing; Cardiac; Cardiac Catheterization Procedures; Cessation of life; Clinical; Clinical Trials; Combined Modality Therapy; Consensus; Data; Development; Diagnosis; Diagnostic; Diffuse; Disease; Disease Progression; Enrollment; Event; Exercise; Failure; Goals; Gold; Heterogeneity; Hypoxia; Image; Imaging Techniques; Intervention; Laboratories; Laboratory Finding; Lung; Magnetic Resonance Imaging; Measurement; Measures; Medical; Monitor; Morphologic artifacts; Motivation; Newly Diagnosed; Noise; Pathway interactions; Patients; Perfusion; Pharmacotherapy; Physiological; Prediction of Response to Therapy; Process; Prognosis; Protocols documentation; Protons; Public Health; Pulmonary Circulation; Pulmonary Hypertension; Race; Regulation; Reporting; Reproducibility; Resistance; Secondary to; Severity of illness; Signal Transduction; Slice; Structure of parenchyma of lung; Surrogate Endpoint; Techniques; Testing; Time; Translating; Translations; Transplantation; Vascular remodeling; Ventricular; Walking; Work; arteriole; candidate marker; cardiac magnetic resonance imaging; data acquisition; drug efficacy; health goals; indexing; individual patient; inhaled nitric oxide; innovation; lung imaging; lung volume; magnetic resonance imaging biomarker; novel therapeutics; outcome prediction; patient biomarkers; perfusion imaging; pressure; prognostic; pulmonary arterial hypertension; pulmonary arterial pressure; pulmonary vascular remodeling; respiratory; right ventricular failure; screening; sex; single photon emission computed tomography; symposium; tool; treatment response; ventilation

PROJECT SUMMARY Goal/Significance. Pulmonary arterial hypertension (PAH) arises from progressive remodeling of the pulmonary circulation leading to the secondary effects of elevated pulmonary arterial pressure and resistance after 50% of vessels are affected. The leads to increased afterload, followed by right heart failure and death. Improvement in medical therapy in PAH is related to the development of new drugs and combination therapies rather than the identification of new pathways. This proposal meets a critical need for tools that will better identify those who respond to these new therapies. The goal of this proposal is to translate and refine biomarkers derived from proton magnetic resonance imaging (MRI), and evaluate their sensitivity to predict disease progression in patients with PAH. Scientific Premise. Functional proton MRI may provide increased sensitivity to disease progression because of the ability to detect local changes related to vascular remodeling that is obscured by regions of normal lung. Innovation/Hypothesis. Building on our previous work developing innovative proton MRI biomarkers that are markedly altered in patients with established PAH, we predict that the onset of PAH manifests as a progressive alteration in images of the pulmonary circulation as follows: 1. an increase in un-perfused lung regions as vessels succumb to remodeling 2. a resultant increase in the spatial heterogeneity of perfusion and 3. an increase in fluctuations in perfusion reflecting a failure of local pressure regulation. Our selected biomarkers reflect these processes. We hypothesize that these biomarkers are altered in patients with PAH, with disease progression, by physiological changes induced by therapy and are early predictors of outcome. Approach. Supported by our preliminary data we will: 1. Determine the sensitivity of proton MRI biomarkers for patients with established PAH receiving therapy, evaluate biomarkers as a measures of disease severity and compare these to clinical findings, and cardiac MRI (CMR) data. 2. optimize image acquisition protocol efficiency to facilitate translation. Evaluate reproducibility, and effects of noise and artifacts. 3. Evaluate proton MRI biomarkers as a means to monitor response to therapy by longitudinally monitoring newly diagnosed PAH patients and assess the ability of lung biomarkers to predict time to clinical worsening compared to CMR, and current standards. Impact. Successful completion of this work will lead to new monitoring tools for patients with PAH using noninvasive proton MRI, potentially providing prognostic information in patients with PAH. The techniques proposed here could be ultimately conducted on any 1.5 T clinical MRI scanner in less than 30 minutes, increasing utility for screening.

项目概要 目标/意义。肺动脉高压（PAH）是由肺动脉的进行性重塑引起的。 肺循环导致肺动脉压升高的继发效应 50%的血管受到影响后的阻力。导致后负荷增加，随后出现右心衰竭 和死亡。 PAH 药物治疗的改进与新药的开发和 联合疗法而不是识别新途径。该提案满足了关键需求 寻找能够更好地识别那些对这些新疗法有反应的人的工具。该提案的目标是 翻译和精炼源自质子磁共振成像 (MRI) 的生物标志物，并评估其 预测 PAH 患者疾病进展的敏感性。 科学前提。功能质子 MRI 可能会提高对疾病进展的敏感性，因为 检测与血管重塑相关的局部变化的能力，这些变化被正常区域所掩盖 肺。 创新/假设。以我们之前开发创新质子 MRI 生物标志物的工作为基础 在已确诊的 PAH 患者中发生显着改变，我们预测 PAH 的发作表现为 肺循环图像进行性改变如下： 1. 肺未灌注量增加 血管屈服于重塑的区域 2. 灌注空间异质性的结果增加 3. 灌注波动增加，反映局部压力调节失败。我们精选的 生物标志物反映了这些过程。我们假设这些生物标志物在 PAH 患者中发生了改变， 随着疾病的进展，治疗引起的生理变化是结果的早期预测因素。 方法。在我们的初步数据支持下，我们将： 1. 确定质子 MRI 生物标志物的敏感性 对于已经接受治疗的 PAH 患者，评估生物标志物作为疾病严重程度的衡量标准 并将这些结果与临床发现和心脏 MRI (CMR) 数据进行比较。 2.优化图像采集协议 效率有利于翻译。评估再现性以及噪声和伪影的影响。 3. 评估 质子 MRI 生物标志物作为通过纵向监测新来监测治疗反应的一种手段 诊断 PAH 患者并评估肺部生物标志物预测临床恶化时间的能力 与 CMR 和现行标准相比。 影响。这项工作的成功完成将为 PAH 患者带来新的监测工具 无创质子 MRI，可能为 PAH 患者提供预后信息。技巧 这里提出的建议最终可以在任何 1.5 T 临床 MRI 扫描仪上在 30 分钟内完成， 增加筛查的效用。