MRI Phenotyping of Early BPD and Prediction of Outcomes

项目摘要 支气管肺发育不良（BPD）是一种慢性早产儿疾病，其患病率正在增加， 负责全国大多数新生儿重症监护病房（NICU）的入院（超过 在美国每年130亿美元），并且具有高死亡率和发病率。患有BPD的儿童肺功能下降 肺血管疾病和包括哮喘在内的终身呼吸道疾病的发病率增加 和COPD，初步诊断和结果之间没有明确的联系。目前，BPD的定义是 补充氧气的需求，但这种简单的定义未能考虑到多因素的复杂性 疾病及其进展的信息多个团体试图根据功能和 生理信息，但这些定义未能确定那些早产儿谁发展BPD或如何 疾病会发展。唯一确定的BPD结局预测因素之一是肺动脉 高血压（PAH），但PAH本身的诊断是模糊的，往往延误，因为超声心动图， 在这些过度充气的患者中可能不准确。缺乏BPD严重的临床预后定义， 限制了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。 为了解决这一未满足的需求，以评估心肺病理，我们的团队率先使用MRI在 新生儿重症监护病房量化早产儿的心脏、肺和气道异常。我们的超短- 超声心动图（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 从CT，不需要电离辐射或造影剂注射，并可以进行自由呼吸的新生儿 没有镇静剂。此外，该MRI提供了关于肺实质和脉管系统的结构信息 以及来自心脏和气道的动态生理信息，这些信息以前从未在 新生儿基于强大的初步数据和我们证明的临床相关能力， 在新生儿心肺MRI，我们将定义BPD表型来自结构和功能 患者中普遍存在的异常。在此过程中，我们将首次确定特定的结构-功能 这些异常对应于BPD中的局部病理生理学和患者结果。 我们的总体目标是通过MRI表型来描述早产的早期后遗症， 通过纵向MRI评估疾病的时间进程，预测NICU出院时或出院附近的呼吸结局， 早期临床护理和影像表型对1年和2年呼吸结局的影响。该提案借鉴了 强大的初步数据和多学科的临床和研究计划，以建立第一个图像衍生的 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，有很强的预防潜力，影响我们对疾病的理解和定义， 形成，可能对未来的呼吸支持，重症监护和结果产生影响。

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.