White Matter Injury in Critical Ill Newborns With Congenital Heart Disease

该项目的总体目标是使用多学科方法和先进的磁共振 通过MRI来了解导致危重患者神经发育障碍的机制， 新生儿先天性心脏病（CHD）。我们小组和其他人的数据表明， 发育中的脑白色物质在患有CHD的新生儿中是常见的。这种白色物质损伤的外观是 与早产儿相同，在新生儿手术前后发现损伤。我们 这项研究的重点是两种最常见的先天性心脏病： 动脉（TGA）和单心室生理学（SVP），因为这两种情况都与异常 胎儿脑血流和出生后导管依赖性循环。我们最近确定， 这些新生儿的大脑微结构和代谢的成熟延迟，在手术前， 是由于子宫内大脑发育受损造成的在本提案中，我们将测试延迟的假设。 宫内脑发育使CHD新生儿易受围手术期白色损伤 侮辱。我们已经开发出基本的方法来安全地测量大脑发育，损伤和围手术期 CHD胎儿和新生儿的氧气输送。使用这些工具，我们能够解决我们的整体问题， 目的是确定子宫内大脑发育延迟是否是足月妊娠特定脆弱性的基础。 新生儿CHD与白色损害的关系。为此，我们提出了两个具体目标：（1）表征大脑 在患有TGA的足月新生儿中，子宫内和出生后、心脏手术前后的发育和损伤 和SVP。(2)确定白色损伤的风险是否与脑氧输送受损有关 （近因），在大脑微结构和代谢发育延迟的情况下。这 多学科项目结合了儿科重症监护，神经病学，神经放射学，心脏病学的专业知识 和心胸外科手术，以确定脑损伤的特定病理生理机制，并开发新的 神经发育结果的预后指标，可以转化为未来的神经保护试验。 页面 作者：帕特里克S.

The overall goal of this project is to use a multidisciplinary approach and advanced magnetic resonance imaging (MRI) to understand mechanisms that result in neurodevelopmental impairment in critically ill newborns with congenital heart disease (CHD). Data from our group and others have shown that injury to the developing brain white matter is common in newborns with CHD. The appearance of this white matter injury is identical to that seen in premature infants, with injuries identified before and after neonatal surgery. We are focusing this study on two of the most common forms of congenital heart disease: transposition of the great arteries (TGA) and single ventricle physiology (SVP), because both conditions are associated with abnormal fetal cerebral blood flow and postnatal ductal dependent circulation. We have recently determined that maturation of cerebral microstructure and metabolism are delayed in these newborns, prior to surgery, possibly as a result of impaired in utero brain development. In this proposal we will test that hypothesis that delayed in utero brain development predisposes newborns with CHD to white matter injury in response to perioperative insults. We have developed essential methods to safely measure brain development, injury and perioperative oxygen delivery in fetuses and newborns with CHD. Using these tools, we are positioned to address our overall objective of determining if delayed in utero brain development underlies the specific vulnerability of term newborns with CHD to white matter injury. To do this, we propose two specific aims: (1) To characterize brain development and injury in utero and postnatally, before and after cardiac surgery, in term newborns with TGA and SVP. (2) To determine if the risk of white matter injury is related to impaired brain oxygen delivery (proximate cause), in the setting of delayed brain microstructural and metabolic development. This multidisciplinary project combines the expertise of pediatric critical care, neurology, neuroradiology, cardiology and cardiothoracic surgery to identify specific pathophysiologic mechanisms of brain injury and develop novel prognostic measures of neurodevelopmental outcome that can be translated into future neuroprotective trials. Page McQuillen, Patrick S.