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

项目总结 尽管在新生儿和神经外科护理方面取得了进展，但出血性脑积水仍是 早产最常见的严重神经系统并发症(出生时胎龄≤32周)和 现在是北美儿童脑积水的最常见原因。它还携带着一件沉重的 神经发育障碍，超过75%的患者被诊断为认知障碍和/或脑性瘫痪 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 以优化出血性脑积水的神经外科治疗为中心，重点是缓解 由于进行性脑室扩张造成的持续性损伤，这是长期以来公认的不良预后的危险因素。这个 这项建议的目的是明确出血后脑积水的病理生理影响。 大脑连通性和神经预后，更具体地说，确定脑室容量 修改这些关系。我们的中心假设是：1)结构和功能连通性受损 跨关键的白质束(如皮质脊髓束、光辐射、胼胝体)和相关的功能 网络(例如，躯体运动、视觉、默认模式网络)与后遗症的神经功能障碍有关 出血性脑积水，2)脑室扩张与出血性脑积水相关 连接性缺陷，以及3)这些连接性改变随着神经外科脑室的改善而改善 解压。磁共振成像的最新进展现在可以表征功能和结构的连通性 在发育中的大脑中具有无与伦比的空间和时间分辨率。这些数据的分析使用高度的 创新的基于扩散的光谱成像方法提供了独特的能力来表征复杂的 大脑连通性的这些差异背后的神经病理变化。在这里，我们的多学科团队 将使用这些最先进的核磁共振技术，并结合详细的神经发育评估 研究一大群(N=180)早产儿，包括有或没有出血后的早产儿 新生儿重症监护室出院后前瞻性招募和纵向随访的脑积水 护理室。此外，患有出血性脑积水的婴儿将接受神经成像研究 脑脊液分流手术前后对脑连通性的可逆性影响 同时也确定了脑室大小在其病理中的作用。这些尖端磁共振成像采集技术的应用 而分析方法能够前所未有地表征出血后的影响 大脑发育中的脑积水。此外，我们将扩展这些方法以描述 影像测量和神经发育结果，提高我们对可改变的影响的理解 这种毁灭性的疾病。关键的是，这些结果将解决长期存在的、与临床相关的重要问题。 护理出血后脑积水的婴儿，并提供创新评估的发展信息 支持临床试验的工具，这些试验试图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.