Imaging neonatal Hypoxic Ischemic Injury

描述（由申请人提供）：缺氧缺血性（HI）损伤早产儿白质和灰质，并导致显著的死亡率和发病率。为探讨新生儿缺氧缺血性损伤的病理机制，寻求满意的治疗方法，建立了新生儿缺氧缺血性损伤动物模型并广泛应用。在这个项目中，新的体内磁共振成像和计算技术将用于检查新生儿小鼠模型HI损伤的时空演变。纵向多对比MRI数据将被收集和分析，并在基于我们的基于发育中的小鼠大脑的MR图谱的共同框架中使用共同注册的终点组织学数据。在目的1中，我们将使用体内MRI/组织学联合分析来检查灰质和白质损伤。在目标2中，我们将使用振荡梯度扩散MRI和组织学检查皮层、海马和小脑的神经变性。在目的3中，我们将在中心框架中整合纵向多造影MRI数据和组织学数据，以表征新生儿HI损伤的时空进展及其区域特异性。然后，我们将使用这里开发的工具来表征缺乏功能性Fas死亡受体的小鼠HI损伤。我们还将在该模型中检查坏死性他汀的神经保护作用。我们希望该项目能够提供详细的损伤时间过程和区域易感性图，扩展我们对小鼠模型中病理和诊断标志物之间关系的认识，并阐明HI损伤的机制和潜在的治疗方法。本项目开发的信息和技术将有助于设计有效的干预策略，并在使用该模型或类似模型的研究中监测治疗反应。

DESCRIPTION (provided by applicant): Hypoxic ischemic (HI) insult damages premature white matter and grey matter in infants and causes significant mortality and morbidity. To investigate the pathological mechanisms of neonatal HI injury and find satisfactory treatments, animal models of neonatal hypoxic ischemic injury have been established and widely used. In this project, novel in vivo magnetic resonance imaging and computational techniques will be used to examine the spatiotemporal evolution of HI injury in a neonatal mouse model. Longitudinal multi-contrast MRI data will be collected and analyzed with co-registered end-point histological data in a common framework based on our MR based atlas of the developing mouse brain. In aim 1, we will examine grey and white matter injury using in vivo MRI/histology combined analysis. In aim 2, we will examine neurodegeneration in the cortex, hippocampus, and cerebellum using oscillating gradient diffusion MRI and histology. In aim3, we will integrate the longitudinal multi-contrast MRI data with histological data in the central framework to characterize the spatiotemporal progression of neonatal HI injury and its regional specificity. We will then use the tools developed here to characterize HI injury in mice lacking functional Fas death receptor. We will also examine the neuroprotective effects of necrostatin in this model. We expect the project to provide detailed maps of temporal course of injury and regional susceptibility, extend our knowledge on the relationships between pathology and diagnostic markers in the mouse model, and shed light on the mechanisms of HI injury and potential treatments. This information and techniques developed in this project will be useful to design effective strategies for intervention and to monitor treatment response in studies using this or similar models.