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.

项目概要尽管新生儿和神经外科护理取得了进步，但出血后脑积水仍然是最常见的疾病之一。极早产（出生胎龄≤32周）最常见、严重的神经系统并发症现在是北美儿童脑积水的最常见原因，它也带来了沉重的负担。神经发育损害，超过 75% 的受影响者被诊断为认知缺陷和/或脑瘫在医学方法未能解决其神经系统后遗症后，最近的研究发现。以优化出血后脑积水的神经外科治疗为中心，重点是减轻进行性心室扩张导致持续损伤，这是长期以来公认的不良结果的危险因素。该提案的目的是确定出血后脑积水对患者的病理生理学影响大脑连接和神经系统结果，更具体地说，确定心室容量我们的中心假设是：1）结构和功能连接受损。跨越关键白质束（例如皮质脊髓束、视辐射、胼胝体）和相关功能网络（例如，躯体运动网络、视觉网络、默认模式网络）与术后神经功能障碍有关。出血性脑积水，2）脑室扩张导致出血后脑积水相关连接性缺陷，3）这些连接性改变通过神经外科心室改善 MRI 的最新进展现在可以表征功能和结构连接。在发育中的大脑中使用高度的空间和时间分辨率分析这些数据。创新的扩散基础光谱成像方法提供了独特的能力来表征复杂的这些大脑连接差异背后的神经病理变化在这里，我们的多学科团队。将采用这些最先进的 MRI 技术并结合详细的神经发育评估研究一个大型队列 (N=180)，其中包括患有或不患有出血后症状的极早产儿新生儿重症监护室出院后前瞻性招募脑积水患者并进行纵向随访此外，患有出血后脑积水的婴儿将接受神经影像学检查。脑脊液分流手术前后，表征对脑连接的可逆影响同时还定义了心室大小在其病理学中的作用。和分析方法能够前所未有地表征出血后的影响此外，我们将扩展这些方法来描述脑积水之间的关系。成像测量和神经发育结果，提高我们对可改变影响的理解至关重要的是，这些结果将解决长期存在的、临床上重要的相关问题。护理患有出血后脑积水的婴儿并为创新评估的发展提供信息支持旨在阻止这一高风险人群中观察到的发育障碍的临床试验的工具。