UNDERSTANDING NEUROBEHAVIORAL DEFICITS IN PRETERM INFANTS THROUGH IMAGING

描述（由申请人提供）：早产是一个主要的公共卫生问题，因为其发病率不断上升，并且幸存婴儿随后经常面临行为、神经和精神方面的挑战。大约10-15%的极早产儿（出生时胎龄< 30周）会发生脑瘫，30 - 60%的极早产儿会出现认知障碍。这些障碍包括视觉运动问题、注意力困难、记忆受损、语言习得延迟、执行功能障碍、学习障碍、社交技能差、社交退缩、焦虑和抑郁的高发率。此外，在早产儿中，发育障碍如注意力缺陷/多动障碍、自闭症和精神分裂症的患病率有所增加。这些不良后果与新生儿期持续的白质（WM）和灰质（GM）损伤及其对随后大脑发育的影响有关。我们寻求开发在婴儿期可测量的成像生物标志物，为识别有不良神经发育结果风险的婴儿提供敏感性和特异性。生物标志物将包括以下磁共振成像测量：1)常规T1和t2加权图像，2)体积测量（皮质GM、深部核GM、有髓鞘WM、无髓鞘WM和脑脊液的体积），3)扩散张量成像（表观扩散系数、相对各向异性、轴向和径向扩散率），以及4)基于表面的形态测量（综合折叠指数、平均沟深、皮质表面积、埋藏皮层百分比）。本研究的主要队列将包括120名胎龄< 30周的极早产儿。他们将在出生后不久，经后30周（PMA），经后34周（PMA）和足月等值时进行MR研究。在第一年入组的婴儿（n = 30）也将在4岁时进行影像学检查。将上述磁共振指数与健康对照者的磁共振数据以及足月及2岁和4岁时获得的临床结果数据进行比较。提出的研究旨在加深对脑损伤的性质和时间的理解，为神经保护策略的发展和改善临床实践奠定基础。纵向设计将允许我们研究结构异常和对损伤反应的代偿变化。在新生儿时期对发育不良的高风险婴儿进行识别，将有助于及早针对这些婴儿提供治疗服务。如果取得成功，拟议的研究将改善早产儿的预后。项目简介：本研究旨在利用磁共振成像技术提高我们对早产儿脑损伤的认识。这种认识有可能改善临床实践，并协助开发药物来减少这些婴儿的伤害，最终减少残疾。它还将有助于确定那些患有脑瘫或智力迟钝的高风险婴儿，以便为他们提供早期治疗服务。

DESCRIPTION (provided by applicant): Preterm birth is a major public-health issue because of its increasing incidence combined with the frequent occurrence of subsequent behavioral, neurological, and psychiatric challenges faced by surviving infants. Approximately 10-15% of very preterm children (born < 30 weeks gestational age) develop cerebral palsy, and 30 - 60% of very preterm children experience cognitive impairments. These impairments include visual-motor problems, attentional difficulties, impaired memory, delayed acquisition of language, executive dysfunction, learning disabilities, poor social skills, and higher rates of social withdrawal, anxiety and depression. In addition, an increased prevalence of developmental disorders such as attention deficit/hyperactivity disorder, autism and schizophrenia, has been described in the preterm population. These adverse outcomes are related to white matter (WM) and grey matter (GM) injury sustained during the neonatal period and its effects on subsequent brain development. We seek to develop imaging biomarkers, measurable during infancy, that provide sensitivity and specificity in identifying infants at risk for poor neurodevelopmental outcome. The biomarkers will consist of the following magnetic resonance (MR) imaging measures: 1) conventional T1- and T2-weighted images, 2) volumetry (volumes for cortical GM, deep nuclear GM, myelinated WM, unmyelinated WM, and cerebrospinal fluid), 3) diffusion tensor imaging (apparent diffusion coefficient, relative anisotropy, axial and radial diffusivity), and 4) surface-based morphometry (integrated folding index, average sulcal depth, cortical surface area, percentage of buried cortex). The main cohort of this study will consist of 120 very preterm infants born < 30 weeks gestational age. They will undergo MR studies soon after birth, at 30 weeks postmenstrual age (PMA), 34 weeks PMA, and term equivalent. Infants enrolled during Year 1 (n = 30) will also be imaged at age 4 years. The MR indices listed above will be compared with MR data from healthy control subjects and clinical outcome data obtained at term equivalent and 2 and 4 years of age. The proposed studies are designed to engender a deeper understanding of the nature and timing of cerebral injury, laying the groundwork for the development of neuroprotective strategies and improving clinical practices. The longitudinal design will allow us to study both structural abnormalities and compensatory changes in response to injury. Identification during the newborn period of infants at high risk for poor developmental outcome will allow early targeting of therapy services to these infants. If successful, the proposed studies will lead to improved outcomes for prematurely-born infants. Project Narrative: This study is designed to use magnetic resonance imaging to improve our understanding of the brain injury sustained by prematurely-born infants. This understanding has the potential to improve clinical practices and assist with the development of medications to reduce injury in these babies, ultimately reducing disabilities. It will also help identify those infants who are at high risk for developing cerebral palsy or mental retardation so they can be provided early access to therapy services.