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，因为它的发病率不断增加，并经常发生随后的行为，神经和精神方面的挑战所面临的幸存婴儿。大约10-15%的极早产儿（胎龄< 30周）会患脑瘫，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、记忆力受损、语言习得延迟、执行功能障碍、学习障碍、社交技能差以及社交退缩、焦虑和抑郁的比例较高。此外，在早产儿人群中，注意力缺陷/多动障碍、自闭症和精神分裂症等发育障碍的患病率有所增加。这些不良结局与新生儿期持续的白色物质（WM）和灰质（GM）损伤及其对随后脑发育的影响有关。我们寻求开发在婴儿期可测量的成像生物标志物，其在识别具有不良神经发育结果风险的婴儿方面提供灵敏度和特异性。生物标志物将包括以下磁共振（MR）成像测量：1）常规T1和T2加权图像，2）容量测定（皮质GM、深核GM、有髓WM、无髓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）基于表面的形态测定（综合折叠指数、平均沟深度、皮质表面积、埋藏皮质百分比）。本研究的主要队列将由120名胎龄< 30周的极早产儿组成。他们将在出生后不久，在30周的月经后年龄（PMA），34周的PMA，和长期等效进行MR研究。第1年入组的婴儿（n = 30）也将在4岁时进行成像。将上述MR指数与健康对照受试者的MR数据以及在足月、2岁和4岁时获得的临床结局数据进行比较。拟议的研究旨在更深入地了解脑损伤的性质和时间，为制定神经保护策略和改善临床实践奠定基础。纵向设计将使我们能够研究结构异常和对损伤的代偿性变化。在新生儿期发现发育不良风险高的婴儿，可及早为这些婴儿提供治疗服务。如果成功，拟议的研究将改善早产儿的结局。 项目叙述：本研究旨在利用磁共振成像来提高我们对早产儿脑损伤的认识。这种理解有可能改善临床实践，并协助开发药物，以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有患脑瘫或智力迟钝高风险的婴儿，以便为他们提供抢先体验治疗服务。

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.