MRI Phenotyping of Early BPD and Prediction of Outcomes

项目总结 支气管肺发育不良(BPD)是一种慢性早产儿疾病，患病率正在上升，是 负责全国大部分新生儿重症监护病房(NICU)的入院工作(超过 在美国为130亿美元/年)，并且死亡率和发病率很高。患有BPD的儿童肺活量减少 功能，肺血管疾病的发病率增加，以及包括哮喘在内的终身呼吸系统疾病 和慢性阻塞性肺病，在初始诊断和结果之间没有明确的联系。目前，BPD定义为 补充氧量，但这个简单的定义没有考虑到多因素的复杂性 疾病及其发展的最新进展。多个小组已尝试根据功能和 生理信息，但这些定义未能识别出哪些早产儿或如何发展为BPD。 疾病会继续发展。唯一确定的预测BPD预后的指标之一是肺动脉。 高血压(PAH)，但PAH本身的诊断是模棱两可的，而且经常被延误，因为超声心动图 在这些过度膨胀的患者身上可能是不准确的。严重缺乏BPD的临床预后定义 限制预测结果或评估旨在改善短期和长期结果的干预措施的能力。 为了解决这一未得到满足的评估心肺病理的需求，我们的团队率先在 NICU用于量化早产儿的心脏、肺和呼吸道异常。我们的超短裤- 回波(UTE)技术以类似于CT的分辨率生成3D图像，提供不可用的功能信息 CT不需要电离辐射或造影剂注射，可以在自由呼吸的新生儿身上进行 没有镇静剂。此外，MRI还提供了有关肺实质和血管系统的结构信息 以及来自心脏和呼吸道的动态生理信息，这是以前从未在 新生儿。基于强大的初步数据和我们证明的临床相关能力 在新生儿的心肺MRI中，我们将根据结构和功能来定义BPD的表型 患者中普遍存在的异常现象。在这样做的过程中，我们将首次确定具体的结构-功能 BPD的异常与局部病理生理学和患者预后相对应。 我们的总体目标是通过MRI表型来表征早产的早期后遗症，确定 通过纵向MRI预测NICU出院时或出院附近的呼吸结果，并与 早期临床护理和影像表型对1年和2年后的呼吸结果的影响。这项建议借鉴了 强大的初步数据和多学科的临床和研究计划，建立了第一个图像派生的 BPD的表型，在疾病形成和迅速变化的生命阶段。研究的影响 是高的，并具有很强的翻译潜力-影响我们对疾病及其 形成，可能对未来的呼吸支持、危重护理和预后产生影响。

PROJECT SUMMARY Bronchopulmonary Dysplasia (BPD) is a chronic disease of prematurity that is increasing in prevalence, is responsible for the majority of neonatal intensive care unit (NICU) admissions across the nation (more than $13B/year in the US), and has high mortality and morbidity. Children with BPD have decreased pulmonary function, increased incidence of pulmonary vascular disease, and lifelong respiratory illnesses including asthma and COPD, with no clear link between initial diagnosis and outcomes. Currently, BPD is defined in terms of supplementary oxygen requirement, but this simplistic definition fails to account for the multifactorial complexity of the disease and its progression. Multiple groups have attempted to define BPD based on functional and physiologic information, but these definitions fail to identify those premature infants who develop BPD or how disease will progress. One of the only established outcomes predictors for BPD is pulmonary arterial hypertension (PAH), but the diagnosis of PAH itself is ambiguous and often delayed, because echocardiography can be inaccurate in these hyperinflated patients. The lack of a clinically prognostic definition of BPD severely limits the ability to predict outcomes or evaluate interventions designed to improve short and long term outcomes. To address this unmet need to assess cardio-respiratory pathology, our team pioneered the use of MRI in the NICU to quantify cardiac, pulmonary and airway abnormalities in prematurely-born neonates. Our ultra-short- echo (UTE) techniques yield 3D images at resolutions similar to CT, provide functional information unavailable from CT, require no ionizing radiation or contrast injection, and can be performed on free-breathing neonates without sedation. Further, this MRI provides structural information about the lung parenchyma and vasculature and dynamic physiologic information from the heart and airways that has never before been available in neonates. Based on strong preliminary data and our demonstrated ability to perform clinically relevant cardiopulmonary MRI in neonates, we will define BPD phenotypes derived from structural and functional abnormalities prevalent in patients. In doing so, we will determine for the first time how specific structure-function abnormalities correspond to regional pathophysiology and patient outcomes in BPD. Our overall goal is to characterize the early sequelae of premature birth via MRI phenotyping, determine the timecourse of disease via longitudinal MRI, predict respiratory outcomes at or near NICU discharge, and relate early clinical care and image phenotyping to 1- and 2-year respiratory outcomes. This proposal draws upon strong preliminary data and multidisciplinary clinical and research programs to establish the first image-derived phenotypes of BPD, in the stage of life when the disease forms and changes rapidly. The impact of the research is high and has strong potential for translation—affecting our understanding and definition of disease and its formation, with likely impact on future respiratory support, critical care, and outcomes.