Imaging of pulmonary arterial hypertension with proton MRI

项目总结 目标/意义。肺动脉高压(PAH)是由血管的进行性重构引起的。 肺循环导致肺动脉压升高和继发效应 50%的血管受到影响后产生阻力。这会导致后负荷增加，随后是右心衰竭 和死亡。PAH药物治疗的改进与新药的开发和 联合疗法，而不是确定新的治疗途径。这项建议满足了一项迫切的需要 寻找工具，更好地识别那些对这些新疗法有反应的人。这项提议的目标是 翻译和提纯来自质子磁共振成像(MRI)的生物标记物，并评估其 预测PAH患者疾病进展的敏感性。 科学前提。功能性质子磁共振成像可以提高对疾病进展的敏感性，因为 能够检测与血管重塑相关的局部变化，这些变化被正常区域遮挡 阿龙。 创新/假设。在我们之前工作的基础上，开发创新的质子磁共振生物标记物 在确诊的PAH患者中显著改变，我们预测PAH的发病表现为 肺循环影像的进行性改变如下：1.无灌注肺增多 作为血管的区域屈从于重塑2。结果增加了血流灌注的空间异质性。 3.血流灌注波动增加，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记物在PAH患者中发生了改变， 随着疾病的进展，由治疗引起的生理变化，是预后的早期预测因素。 接近。在我们初步数据的支持下，我们将：1.确定质子磁共振生物标记物的灵敏度 对于接受治疗的已确诊的PAH患者，评估生物标记物作为衡量疾病严重程度的指标 并将这些结果与临床表现和心脏磁共振(CMR)数据进行比较。2.优化图像采集协议 效率，以方便翻译。评估重复性以及噪声和伪影的影响。3.评估 质子磁共振生物标志物作为纵向监测新的治疗反应的手段 诊断PAH患者并评估肺生物标记物预测临床恶化时间的能力 与CMR相比，以及现行标准。 冲击力。这项工作的成功完成将为PAH患者带来新的监测工具 无创性质子磁共振成像，潜在地提供了PAH患者的预后信息。这些技术 这里提出的最终可以在任何1.5T临床磁共振扫描仪上在不到30分钟内进行， 增加筛查的效用。

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.