Comprehensive Clinical Assessment of Pediatric PHT

描述（由申请人提供）： 肺动脉高压（PAH）是一种对儿童了解相对较少的疾病，需要持续监测和长期治疗，以减轻过度的右心室后负荷效应。这种监测需要定期和频繁的侵入性临床成像会话。然而，即使使用有创技术，目前获得的临床信息的程度也是不完整的，主要涉及肺血管阻力（PVR）及其组成参数：平均肺动脉（PA）压力和右侧心输出量（Qp）。鉴于目前可用于临床评估PAH的定量信息的缺乏，存在使用先进的心血管成像和复杂的计算建模相结合来开发和评估更全面的PAH指标的机会。此外，从这些努力中获得的信息也应该有助于开发新的非侵入性诊断，通过允许更容易地获取肺血管特征、连续监测和床旁反应性评估，应该扩大临床医生表征这种复杂疾病的能力。这些研究的总体假设是，肺血管输入阻抗提供了比单独PVR更全面的肺血管功能测量，因为阻抗包括血管回路的动态（刚度或顺应性）和稳态（阻力）分量。因此，该项目的目的分为建立阻抗临床使用的研究，探索为什么阻抗是肺血管血流动力学和力学的良好反映的研究，以及开发提取有创测量中发现的相关参数的新型无创诊断的研究。 阻抗，即PVR和肺血管硬度（PVS）。该K24项目提出了研究和培训工作的独特组合，以推进PAH的临床评价，同时培训临床研究人员对基础物理学和血液动力学有坚实的基本理解，并将这些原理准确应用于新型临床诊断。

DESCRIPTION (provided by applicant): Pulmonary arterial hypertension (PAH) is a relatively poorly understood disease in children and requires constant monitoring and chronic treatment to mitigate excess right ventricular afterload effects. Such monitoring requires regular and frequently invasive clinical imaging sessions. However, even with invasive techniques, the extent of clinical information currently obtained is incomplete, involving primarily pulmonary vascular resistance (PVR) and its component parameters: mean pulmonary artery (PA) pressure and right sided cardiac output (Qp). Given this paucity of quantitative information currently available to evaluate PAH clinically, opportunities exist to develop and evaluate more comprehensive measures of PAH using a combination of advanced cardiovascular imaging and sophisticated computational modeling. Furthermore, information gained from such endeavors should also assist in the development of novel non-invasive diagnostics, which by allowing easier acquisition of pulmonary vascular characteristics, serial monitoring, and bedside evaluation of reactivity, should widen the clinician's ability to characterize this complex disease. The overall hypothesis for these studies is that pulmonary vascular input impedance provides a more comprehensive measure of pulmonary vascular function than PVR alone since impedance includes both dynamic (stiffness or compliance) and steady-state (resistance) components of the vascular circuit. The aims of this project are therefore divided into studies establishing the use of impedance clinically, studies exploring why impedance is a good reflector of pulmonary vascular hemodynamics and mechanics, and studies developing novel non-invasive diagnostics that extract the relevant parameters found in invasivelymeasured impedance, namely PVR and pulmonary vascular stiffness (PVS). This K24 project proposes a unique combination of research studies and training efforts to advance clinical evaluation of PAH while training clinical research fellows with both solid fundamental understanding of underlying physics and hemodynamics and accurate application of such principles to novel clinical diagnostics.