Non-invasive Assessment of Pulmonary Vascular Structure/Function by MRI in Children with Pulmonary Arterial Hypertension

项目摘要 肺动脉高压（PAH）是一种无法治愈的进行性疾病， 包括成人和儿童。虽然成人和成人之间存在许多病理生理学相似性， 儿童肺动脉高压，儿童的生命年数损失要大得多 因为长期生存有限。儿童PAH与成人疾病的不同在于， 初始损伤发生在成熟和肺发育的关键时期。血流动力 发育中的肺的异常可能影响治疗反应和 疾病的方式尚未显示;并可能仍然是一个强大的贡献因素， 疾病进展。尽管儿童PAH存在显著的独特因素，但该组的研究 缺乏，迫使使用基于成人的指南和治疗。因此，管理 儿科PAH包括使用侵入性右心导管插入术（RHC）进行连续 诊断/预后评估。连续RHC是昂贵的，使儿童重复 麻醉和过度辐射，重要的是，接受导管插入术的儿童， PAH可能发生灾难性事件，包括心跳呼吸骤停和死亡。尽管 这些挑战是侵入性手术所固有的，没有其他方法可以评估 为儿科患者提供治疗指导。这是缺乏研究的重要因素 和针对性的治疗。 心脏MRI是一种单一的成像模式，可以评估心室和 以及PAH病理生理学中涉及的血管系统，无辐射暴露或 大一点的孩子麻醉。在成人研究中，MRI正在成为一种评估技术 血管功能，包括，最近，涡度和螺旋度的四维（4D）速度- 编码的核磁共振成像MRI还具有评价肺血管结构的能力， 空间分辨率，并可能证明PAH的发育血管变化。我们的整体 假设MRI将反映PAH患者的肺血流动力学状态， 到传统的RHC。我们的长期目标是证明非侵入性成像方式可以 诊断和连续监测PAH儿童，并尽可能减少对RHC的需求。 此外，通过4D MRI，沿着常规MRI，在近端进行了新型血管成像， 血管系统将量化儿童血管功能成熟的显著变化， 呸。磁共振成像可能是一个强大的识别儿童独特的靶向治疗。

Project Summary Pulmonary arterial hypertension (PAH) is an incurable, progressive disease that affects both adults and children. While many pathophysiologic similarities exist between adult and pediatric pulmonary hypertension, the number of life years lost in children is much greater given limited long-term survival. Pediatric PAH is distinct from adult disease in the fact that the initial insult occurs during a critical period of maturation and lung development. Hemodynamic abnormalities in the developing lung may impact treatment response and the natural history of the disease in ways that have not been shown; and can remain a strong contributing factor in disease progression. Despite significant unique factors in pediatric PAH, research of this group is lacking, forcing the use of adult-based guidelines and therapies. As a result, management of pediatric PAH includes using invasive right heart catheterization (RHC) for serial diagnostic/prognostic evaluation. Serial RHC is costly, exposes children to repeated anesthesia and excessive radiation, and importantly, children undergoing catheterization for PAH may have catastrophic events including cardiorespiratory arrest and death. Despite these challenges inherent to an invasive procedure, there is no alternative for evaluating therapeutic direction for pediatric patients. This is a significant factor for the lack of research and targeted therapies for this vulnerable population. Cardiac MRI is the single imaging modality that allows assessment of both the ventricle and the vasculature involved in PAH pathophysiology, without radiation exposure or anesthesia in older children. In adult studies, MRI is emerging as a technique for evaluating vascular function, including, recently, vorticity and helicity by 4-dimensional (4D) velocity- encoded MRI. MRI also has the ability to evaluate the pulmonary vascular structure with high spatial resolution and may demonstrate developmental vascular changes in PAH. Our overall hypothesis is that MRI will reflect pulmonary hemodynamic status in patients with PAH similar to conventional RHC. Our long-range goal is to show that non-invasive imaging modality can diagnose and serially monitor PAH children and possibly minimize the need for RHC. Furthermore, novel vascular imaging by 4D MRI, along with conventional MRI, in the proximal vasculature will quantify significant alterations in maturing vascular function in children with PAH. MRI may be a powerful in identifying targeted therapy unique for children.