MRI Mechanisms of Adverse Outcome in Preterm Infants with Seizures

描述(申请人提供)：越来越多的证据表明，癫痫发作对发育中的大脑有害，但对其对早产儿的影响知之甚少。汉娜·格拉斯博士提出的研究将使用她导师正在进行的纵向队列研究的基础设施，以检查脑损伤、大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怀孕32周的婴儿，在两个新生儿时间点对他们进行核磁共振检查，并跟踪他们整个学龄。目前在这项研究中没有常规的癫痫发作测量，如果没有长期的监测，这个年龄段的癫痫发作很难在临床上发现。为母研究改进癫痫检测将使格拉斯博士能够使用高质量的MRI和该研究的后续数据来调查癫痫发作是否会改变早产儿的大脑发育，并导致神经发育结果受损。这项建议的具体目的是比较早产儿的癫痫特征(存在、发作性脑叶发作、演变等)与：(1)常规MRI上的定性损伤模式；(2)海马体的定量测量(大小、新陈代谢和微结构)；以及(3)发育结果。为了改善癫痫的检测，我们将在家长研究中增加黄金标准的视频-脑电监测。来自母公司研究的MRI数据将用于检查海马体的新测量方法(使用扩散张量成像的体积、微结构，以及使用3D MR光谱成像的代谢物)。这个项目是格拉斯博士申请K23奖项的一部分，格拉斯博士是加州大学旧金山分校神经学和儿科助理教授，正在将自己打造成一名年轻的研究员，从事面向患者的新生儿神经学临床和转化性研究。这一K23奖项将使她能够实现以下职业目标：(1)成为以患者为导向的新生儿神经学研究方面的专家，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调查；以及(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博士组建了一个指导团队，成员包括从事新生儿神经学基础科学和临床研究的Donna Ferriero博士、专注于新生儿神经成像的放射科医生A.James Barkovich，以及两位科学顾问：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专家)。 与公共健康相关：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的人数不断增加，其中许多人面临残疾的风险。了解早产儿癫痫发作的影响将为未来多中心研究测试预防和治疗早产儿癫痫的新策略奠定基础。我们预计，减轻癫痫负担将导致早产后神经发育结果的改善。

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.