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的导师正在进行的纵向队列研究的基础设施，检查脑损伤，脑发育和癫痫发作早产儿结局的磁共振测量。这项家长研究招募了妊娠<32周的婴儿，在两个新生儿时间点对他们进行MRI检查，并跟踪他们到学龄。本研究中目前没有常规的癫痫发作测量，并且在临床上难以检测到该年龄组的癫痫发作，并且没有长期监测。改善母研究的癫痫发作检测将使Glass博士能够使用该研究的高质量MRI和随访数据来研究癫痫发作是否会改变大脑发育并导致早产儿人群的神经发育结果受损。 该建议的具体目的是比较早产儿的癫痫发作特征（存在、发作叶发作、演变等）与：（1）常规MRI上损伤的定性模式;（2）海马的定量测量（大小、代谢和微观结构）;（3）发育结局。为了改善癫痫发作检测，我们将在母研究中增加金标准视频EEG监测。母研究的MRI数据将用于检查海马的新测量值（体积、使用扩散张量成像的微观结构和使用3D MR光谱成像的代谢物）。 该项目是申请K23奖的一部分，Glass博士是加州大学旧金山分校弗朗西斯科的神经病学和儿科学助理教授，她正在成为新生儿神经病学以患者为导向的临床和转化研究的年轻研究者。这个K23奖将使她能够实现以下职业目标：（1）成为新生儿神经病学以患者为导向的研究专家，并发展独立的临床研究生涯;（2）使用先进的MRI方法和EEG对早产儿癫痫发作进行临床研究;（3）在临床研究中实施先进的生物统计方法。为了实现这些目标，Glass博士组建了一个由Donna Ferriero博士和A. James Barkovich（专注于新生儿神经成像的放射科医生）和两位科学顾问：大卫格利登博士（研究设计和生物统计分析专家）和约瑟夫沙利文博士（具有新生儿神经生理学专业知识的癫痫病学家）。 公共卫生相关性：早产占美国分娩的12.5%。护理方面的进步导致重症监护托儿所幸存者人数不断增加，其中许多人面临残疾风险。了解早产儿癫痫发作的影响将为未来多中心研究奠定基础，这些研究将测试预防和治疗这一人群癫痫发作的新策略。我们预计，减少癫痫发作负担将导致改善早产后的神经发育结果。

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). PUBLIC HEALTH RELEVANCE: Preterm birth accounts for 12.5% of deliveries in the United States. Advances in care are resulting in rising numbers of intensive care nursery survivors, many of whom are at risk for disabilities. Understanding the impact of seizures in preterm infants will lay the foundation for future multi-center studies testing new strategies for preventing and treating seizures in this population. We expect that reducing seizure burden will lead to improved neurodevelopmental outcomes following preterm birth.