Effects of ventricular volume and cerebral connectivity on neurological outcomes in preterm intraventricular hemorrhage

心室容量和脑连通性对早产脑室内出血神经系统结局的影响

基本信息

批准号：
10581476
负责人：
David Delmar Limbrick
金额：
$ 63.56万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10581476
关键词：
Address Affect Age Anisotropy Assessment tool Axon Birth Brain Brain Injuries Caring Cerebral Palsy Cerebrospinal fluid shunts procedure Cerebrum Child Childhood Clinical Clinical Management Clinical Trials Cognitive Cognitive deficits Complex Corpus Callosum Corticospinal Tracts Data Data Analyses Development Developmental Disabilities Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Disease Edema Failure Functional Magnetic Resonance Imaging Gestational Age Goals Hemorrhage Hydrocephalus Image Impairment Individual Infant Infant Care Inflammation Injury Intervention Investigation Link MRI Scans Magnetic Resonance Imaging Measures Medical Medicine Methods Modeling Motor Needs Assessment Neonatal Neonatal Intensive Care Units Neurologic Neurologic Dysfunctions Neurological outcome Newborn Infant North America Operative Surgical Procedures Optics Outcome Pathology Patients Pregnancy Premature Birth Premature Infant Preterm brain injury Public Health Radiation Research Rest Risk Risk Factors Role Second Look Surgery Shunt Device Structure Surgical Management Techniques Testing Toddler Ventricular Visual Work adverse outcome brain magnetic resonance imaging cohort density design disability disability risk dysmyelination extreme prematurity functional disability high risk population imaging approach imaging study improved improved outcome innovation interdisciplinary approach intraventricular hemorrhage motor impairment multidisciplinary multimodality myelination neuroimaging neuropathology neurosurgery prospective recruit response social spectrograph temporal measurement tool treatment strategy ultrasound white matter

项目摘要

PROJECT SUMMARY Despite advances in neonatal and neurosurgical care, post-hemorrhagic hydrocephalus remains among the most frequent, severe neurological complications of very preterm birth (gestational age at birth ≤32 weeks) and now represents the most common cause of pediatric hydrocephalus in North America. It also carries a heavy neurodevelopmental toll, with cognitive deficits and/or cerebral palsy diagnosed in greater than 75% of affected children. After the failure of medical approaches to impact its neurological sequelae, recent research has centered on optimizing neurosurgical treatment of post-hemorrhagic hydrocephalus, with a focus on mitigating ongoing injury due to progressive ventricular distension, a long-recognized risk factor for poor outcomes. The objectives of this proposal are to define the pathophysiological effects of post-hemorrhagic hydrocephalus on cerebral connectivity and neurological outcomes and, more specifically, to determine how ventricular volume modifies these relationships. Our Central Hypotheses are that 1) impaired structural and functional connectivity across key white matter tracts (e.g., corticospinal tracts, optic radiations, corpus callosum) and related functional networks (e.g., somatomotor, visual, default mode networks) are associated with neurological disability in post- hemorrhagic hydrocephalus, 2) ventricular distension contributes to post-hemorrhagic hydrocephalus-related connectivity deficits, and 3) these alterations in connectivity improve with neurosurgical ventricular decompression. Recent advances in MRI now enable characterization of functional and structural connectivity in the developing brain with unparalleled spatial and temporal resolution. Analysis of these data using the highly innovative diffusion basis spectrum imaging approach affords unique capabilities to characterize the complex neuropathological changes underlying these differences in cerebral connectivity. Here, our multidisciplinary team will employ these state-of-the-art MRI techniques in combination with detailed neurodevelopmental assessments to study a large cohort (N=180) that includes very preterm infants with and without post-hemorrhagic hydrocephalus prospectively recruited and followed longitudinally after discharge from the Neonatal Intensive Care Unit. In addition, infants with post-hemorrhagic hydrocephalus will undergo neuroimaging studies both before and after cerebrospinal fluid shunt surgery, characterizing the reversible effects on cerebral connectivity while also defining the role of ventricle size in its pathology. Application of these cutting-edge MRI acquisition and analysis approaches enables unprecedented characterization of the effects of post-hemorrhagic hydrocephalus on the developing brain. Further, we will extend these methods to delineate relationships between imaging measures and neurodevelopmental outcomes, improving our understanding of the modifiable effects of this devastating disease. Critically, these results will address long-standing, clinically important questions related to the care of infants with post-hemorrhagic hydrocephalus and inform development of innovative assessment tools to support clinical trials seeking to thwart the developmental disability observed in this high-risk population.

项目摘要尽管新生儿和神经外科护理取得了进步，但后脑部脑积水仍然存在最常见的是，非常早产的严重神经系统并发症（出生时胎龄≤32周）和现在是北美小儿脑积水的最常见原因。它也带有沉重的神经发育通行费，患有认知缺陷和/或脑瘫，诊断为75％以上孩子们。在医学方法未能影响其神经后遗症之后，最近的研究已经集中于优化杀虫后脑积水的神经外科治疗，重点是缓解由于进行性心室延伸而持续的损伤，这是结果不良的危险因素。这该提案的目标是定义后脑部脑积水对病理生理的影响脑连通性和神经系统结果，更具体地说，以确定心室体积修改这些关系。我们的中心假设是1）结构和功能连接受损跨关键的白质区域（例如，皮质脊髓区域，视觉辐射，callosum callosum）和相关功能网络（例如，体积运动，视觉，默认模式网络）与后神经障碍有关出血性脑积水，2）心室膨胀有助于赫德脑头脑积水相关的后脑延伸连通性定义，3）连通性的变化随着神经外科的心室改善减压。 MRI的最新进展现在可以表征功能和结构连接性在发育中的大脑中，具有无与伦比的空间和临时分辨率。使用高度分析这些数据创新的扩散基频谱成像方法具有独特的功能来表征复合体这些脑连通性差异的神经病理学变化。在这里，我们的多学科团队将使用这些最先进的MRI技术与详细的神经发育评估结合研究一个大型队列（n = 180），其中包括有或没有诊断后的非常早产的婴儿从新生儿密集期出院后，前瞻性招募并纵向招募脑积水护理部门。此外，患有咽后脑积水的婴儿将接受神经影像学研究脑脊液分流手术前后，表征对脑连通性的可逆影响同时还定义了通风大小在病理学中的作用。这些尖端的MRI获取的应用和分析方法能够对后诊断后的效果进行前所未有的表征发育中的大脑上的脑积水。此外，我们将把这些方法扩展到划定之间的关系成像测量和神经发育结果，提高我们对可修改作用的理解这种毁灭性的疾病。至关重要的是，这些结果将解决与长期存在的临床重要问题有关为患有诊断后脑积水的婴儿提供护理，并为创新评估的发展提供信息支持临床试验的工具，以阻止在这种高风险人群中观察到的发育障碍。