Research_Project

研究项目

• 批准号: 9750228
• 负责人: Catherine Limperopoulos
• 金额: $ 5.31万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9750228
• 关键词: 3-Dimensional; Acute; Address; Affective; Age; American; Area; Behavioral; Behavioral Medicine; Biological Markers; Biometry; Blood; Brain; Brain Injuries; Brain imaging; Cerebellum; Cerebrum; Child; Child Development; Childhood; Clinical; Cognitive; Complement; Complex; Consult; Critical Illness; Data; Databases; Development; Diagnostic Imaging; Diagnostic radiologic examination; Diffusion; District of Columbia; Doctor of Philosophy; Event; Evolution; Exhibits; Family health status; Fetus; Functional disorder; Future; Gestational Age; Glass; Goals; Growth; Head; Health system; High Prevalence; Image; Impaired cognition; Impairment; Infection; Informatics; Injury; Interruption; Intervention; Laboratory Research; Language; Lead; Learning; Lesion; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Medicine; Mental Retardation and Developmental Disabilities Research Centers; Metabolism; Mood Disorders; Nature; Neonatal; Neurodevelopmental Disability; Neuropsychology; Neurosciences; Outcome; Oxygen; Perfusion; Phenotype; Premature Birth; Premature Infant; Prospective Studies; Psychology; Public Health; Quality of life; Reporting; Research; Research Design; Research Project Grants; Rest; Risk Factors; Role; School-Age Population; Spin Labels; Steroids; Structure; Study Section; Surface; Survivors; Techniques; Therapeutic Intervention; Third Pregnancy Trimester; Time; Universities; autism spectrum disorder; clinical practice; critical period; design; disability; effective intervention; experience; faculty research; fetal; imaging biomarker; improved; in utero; magnetic resonance imaging biomarker; medical complication; modifiable risk; neocortical; neurobehavioral; neuroimaging; neuron loss; nutrition; postnatal; premature; professor; social

RESEARCH PROJECT THE VULNERABLE PRETERM CEREBELLUM: ELUCIDATING MECHANISMS AND CONSEQUENCES OF INJURY Catherine Limperopoulos, Ph.D., Project Director Director, MRI Research of the Developing Brain Director, Advanced Pediatric Brain Imaging Research Laboratory Diagnostic Imaging and Radiology Children’s National Health System Louis-Gilbert Vézina, Ph.D. Director, Pediatric Neuroradiology Children’s National Health System Adre J. du Plessis, MBchB, MPH Chief, Fetal and Transitional Medicine Children National Health System Penny Glass, Ph.D. Director, Child Development Center Center for Neuroscience and Behavioral Medicine Children’s National Health System Lauren Kenworthy, Ph.D. Pediatric Neuropsychologist Director, Center for Autism Spectrum Disorders Children’s National Health System Zungho (Wesley) Zun, Ph.D. MRI Physicist/Research Faculty Advanced Pediatric Brain Imaging Research Laboratory Children’s National Health System Robert J. McCarter Jr., ScD Director of the IDDRC Biostatistics and Informatics Component Head: Research Section of Study Design and Biostatistical Consulting Children’s National Health System Catherine Stoodley, D.Phil. Assistant Professor Psychology and Neuroscience Department American University Abstract Premature birth is a major public health problem, associated with a personal, familial, and societal burden of enormous proportions. The potentially lifelong cognitive, learning and affective-behavioral consequences have become the major determinant of life quality in prematurity survivors, with up to 50% of very premature infants experiencing dysfunction in these domains by school age. Impaired cerebellar development has been recently implicated in this dysfunction. We have described a clinically important, previously under-recognized form of prematurity-related cerebellar parenchymal injury in up to 20% in extremely preterm infants. Recently, our observations have extended beyond the role of parenchymal cerebellar injury to a broader and more prevalent spectrum of cerebellar developmental impairments. We have shown that cerebellar development is (i) markedly accelerated during the third trimester, but (ii) significantly impeded after premature birth, even in the absence of direct cerebellar injury. We refer to this impaired growth as cerebellar developmental impairment (CDI). Complementing this intriguing set of structural observations are our findings of a distinctive long-term neuropsychological profile of cognitive, language, affective and social deficiency, which we have termed the developmental cerebellar cognitive affective disorder. The onset and underlying mechanisms and consequences of prematurity-related CDI remain poorly understood, which in turn have complicated the search for potential therapeutic interventions. We propose to utilize serial, advanced MRI techniques to elucidate the timing, evolution, mechanisms and risk factors of CDI in preterm infants born ≤30 weeks gestational age. Our overarching goal is to identify early MR imaging biomarkers of prematurity-related CDI and the associated clinical factors that lead to specific development disabilities. We plan to leverage our large fetal normative database to compare in-utero fetal and ex-utero preterm cerebellar growth trajectories. These findings will inform specific targets, interventions and timing of future neuroprotective strategies, advance clinical practices, and improve neurodevelopmental outcomes.

研究项目 脆弱的早产儿小脑：阐明机制和 伤害的后果 凯瑟琳·林佩罗普洛斯博士， 项目总监 发育中脑的磁共振研究主任 高级儿科主任 脑成像研究实验室 影像诊断与放射学 儿童国家卫生系统 路易斯-吉尔伯特·维吉纳博士 儿科神经放射科主任 儿童国家卫生系统 Adre J.Du Plessis，MBCHB，公共卫生硕士 胎儿和过渡医学部主任 儿童国家卫生系统 彭妮·格拉斯，博士。 儿童发展中心主任 神经科学和行为科学中心 医学 儿童国家卫生系统 劳伦·肯沃西，博士。 儿科神经心理学家 自闭症谱系障碍中心主任 儿童国家卫生系统 Zung(Wesley)Zun，博士 核磁共振物理学家/研究人员 儿科高级脑成像研究进展 实验室 儿童国家卫生系统 小罗伯特·J·麦卡特，SCD IDDRC生物统计中心主任 和信息学组件 负责人：研究设计和研究部 生物统计学咨询 儿童国家卫生系统 凯瑟琳·斯托德利，D·菲尔。 助理教授 心理学和神经科学系 美国大学 摘要 早产是一个主要的公共卫生问题，与个人、家庭和社会负担有关 巨大的比例。潜在的终生认知、学习和情感行为后果 成为早产儿幸存者生活质量的主要决定因素，高达50%的极早产儿 在学龄前经历这些领域的功能障碍。小脑发育受损是最近发生的 与这一功能障碍有关。我们已经描述了一种临床上重要的，以前没有被认识到的形式 极早产儿中高达20%的早产儿与早产相关的小脑实质损伤。最近，我们的 观察已经超越了实质小脑损伤的作用，扩展到更广泛和更普遍的 小脑发育障碍的谱系。我们已经证明了小脑发育是(一) 在妊娠晚期明显加速，但(Ii)在早产后明显受阻，即使在 无直接小脑损伤。我们将这种发育障碍称为小脑发育障碍。 (CDI)。补充这组耐人寻味的结构观察的是我们对一个独特的长期 认知、语言、情感和社交缺陷的神经心理学特征，我们称之为 发育性小脑认知情感障碍。发病机制和潜在机制 与早产相关的CDI的后果仍然鲜为人知，这反过来又使搜索变得复杂 进行潜在的治疗干预。我们建议利用连续的、先进的磁共振技术来阐明 早产儿≤胎龄30周发生CDI的时间、演变、机制及危险因素我们的 首要目标是确定早产相关CDI的早期磁共振成像生物标记物和相关的 导致特定发育障碍的临床因素。我们计划利用我们巨大的胎儿标准 比较宫内胎儿和宫外早产儿小脑发育轨迹的数据库。这些发现将 告知未来神经保护战略的具体目标、干预措施和时机，推进临床实践， 并改善神经发育结果。