MRI Mechanisms of Adverse Outcome in Preterm Infants with Seizures

描述（由申请人提供）：越来越多的证据表明癫痫发作会损害发育中的大脑，但对早产儿的影响知之甚少。Hannah Glass博士提出的研究将利用她导师正在进行的纵向队列研究的基础设施来检查脑损伤，大脑发育和早产儿癫痫发作的结果的磁共振测量。本研究招募了妊娠<32周的婴儿，在两个新生儿时间点用MRI检查他们，并跟踪他们到学龄。目前在这项研究中没有常规的癫痫发作测量，并且在没有长期监测的情况下，该年龄组的癫痫发作很难在临床上发现。在父母研究中改进癫痫检测将使Glass博士能够使用高质量的MRI和该研究的随访数据来调查癫痫发作是否会改变大脑发育并导致早产儿神经发育受损。本建议的具体目的是比较早产新生儿的癫痫特征（存在，关键叶发病，演变等）：(1)常规MRI上的定性损伤模式；(2)海马的定量测量（大小、代谢和微观结构）；(3)发展结果。为了提高癫痫的检测，我们将在家长研究中加入金标准视频-脑电图监测。来自母体研究的MRI数据将用于检查海马的新测量（体积，使用扩散张量成像的微观结构，以及使用3D磁共振光谱成像的代谢物）。该项目是Glass博士申请K23奖的一部分，她是加州大学旧金山分校神经病学和儿科学助理教授，是一名以患者为导向的新生儿神经病学临床和转化研究的年轻研究者。此次K23奖将使她实现以下职业目标：(1)成为新生儿神经病学以患者为导向研究的专家，并发展独立的临床研究事业；(2)利用先进的MRI方法和脑电图对早产儿癫痫发作进行临床调查；(3)在临床研究中应用先进的生物统计学方法。为了实现这些目标，Glass博士组建了一个指导团队，由Donna Ferriero博士（负责新生儿神经病学的基础科学和临床研究）、a . James Barkovich博士（专注于新生儿神经影像学的放射科医生）和两位科学顾问组成：David Glidden博士（研究设计和生物统计分析专家）和Joseph Sullivan博士（具有新生儿神经生理学专长的癫痫学家）。

DESCRIPTION (provided by applicant): Accumulating evidence suggests that seizures harm the developing brain, however little is known about their impact in preterm infants. Dr. Hannah Glass' proposed research will use the infrastructure of her mentor's ongoing longitudinal cohort study to examine magnetic resonance measures of brain injury, brain development, and outcome in preterm infants with seizures. This parent study enrolls infants born <32 weeks gestation, examines them with MRI at two neonatal time points and follows them through school age. There are currently no routine seizure measurements in this study, and seizures in this age group are difficult to detect clinically and without prolonged monitoring. Improving seizure detection for the parent study will allow Dr. Glass to use the high-quality MRI and follow-up data from that study to investigate whether seizures act to alter brain development and lead to impaired neurodevelopmental outcome in the preterm population. The specific aims for this proposal are to compare seizure characteristics (presence, ictal lobar onset, evolution, etc) in preterm newborns with: (1) qualitatitve patterns of injury on conventional MRI; (2) quantitative measures of the hippocampus (size, metabolism and microstructure); and (3) developmental outcome. To improve seizure detection, we will add gold standard video-EEG monitoring to the parent study. MRI data from the parent study will be used to examine novel measures of the hippocampus (volume, microstructure using diffusion tensor imaging, and metabolites using 3D MR spectroscopic imaging). This project is part of an application for a K23 award for Dr. Glass, an Assistant Professor in Neurology & Pediatrics at the University of California, San Francisco, who is establishing herself as a young investigator in patient-oriented clinical and translational research in neonatal neurology. This K23 award will enable her to accomplish the following career goals: (1) to become expert in patient-oriented research in neonatal neurology and to develop an independent clinical research career; (2) to conduct clinical investigations of seizures in preterm infants using advanced MRI methods and EEG; and (3) to implement advanced biostatistical methods in clinical studies. To achieve these goals, Dr. Glass has assembled a mentoring team comprised of Dr. Donna Ferriero, who conducts basic science and clinical investigations in neonatal neurology), and Dr. A. James Barkovich (a radiologist who focuses on neuroimaging in newborns), and two scientific advisors: Dr. David Glidden (an expert in study design and biostatistical analysis) and Dr. Joseph Sullivan (epileptologist with expertise in neonatal neurophysiology).