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

项目摘要 尽管在新生儿和神经外科护理方面取得了进展，出血后脑积水仍然是 极早产（出生时胎龄≤32周）最常见的严重神经系统并发症，以及 现在是北美小儿脑积水的最常见原因。它还携带着沉重的 神经发育损害，在超过75%的受影响患者中诊断出认知缺陷和/或脑瘫 孩子在医学方法未能影响其神经后遗症之后，最近的研究 以优化出血后脑积水的神经外科治疗为中心， 进行性心室扩张导致的持续性损伤，这是长期公认的不良结局的风险因素。的 本提案的目的是确定出血后脑积水的病理生理效应， 大脑连接和神经系统的结果，更具体地说，以确定心室容量如何 改变这些关系。我们的中心假设是：1）结构和功能连接受损 穿过关键的白色物质束（例如，皮质脊髓束、视放射、胼胝体）和相关功能 网络（例如，躯体运动、视觉、默认模式网络）与术后神经功能障碍相关， 出血性脑积水，2）脑室扩张有助于出血后脑积水相关 连接缺陷，和3）这些连接的改变改善与神经外科心室 减压MRI的最新进展现在可以表征功能和结构连接 在发育中的大脑中以无与伦比的空间和时间分辨率。分析这些数据使用的高度 创新的扩散基础光谱成像方法提供了独特的能力，以表征复杂的 神经病理学变化的基础上这些差异的大脑连接。在这里，我们的多学科团队 将采用这些最先进的MRI技术，结合详细的神经发育评估， 研究一个大型队列（N=180），包括有和无出血后 前瞻性招募脑积水患者，并在从新生儿重症监护室出院后进行纵向随访 监护室。此外，患有出血后脑积水的婴儿将接受神经影像学检查， 脑脊液分流术前后，表征对脑连接的可逆影响 同时也定义了心室大小在其病理学中的作用。这些尖端MRI采集技术的应用 和分析方法，使前所未有的特点后出血的影响， 脑积水对大脑发育的影响此外，我们将扩展这些方法来描述 影像学测量和神经发育结果，提高我们对 这种毁灭性的疾病。重要的是，这些结果将解决长期存在的，临床上重要的问题， 出血后脑积水婴儿的护理，并为创新评估的发展提供信息 支持临床试验的工具，旨在阻止在这一高危人群中观察到的发育障碍。

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.