Imaging Neonatal Hypoxic Ischemic Injury

描述(申请人提供)：缺氧缺血(HI)侮辱损害婴儿的早产儿脑白质和灰质，并导致显著的死亡率和发病率。为了探讨新生儿缺氧缺血性脑损伤的病理机制，寻找有效的治疗方法，建立了新生儿缺氧缺血性脑损伤的动物模型并得到了广泛的应用。在这个项目中，新的活体磁共振成像和计算技术将被用来研究新生小鼠模型中HI损伤的时空演变。纵向多对比MRI数据将被收集，并与共同注册的终点组织学数据在一个公共框架内进行分析，该框架基于我们基于MR的小鼠大脑发育图谱。在目标1中，我们将使用在体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磁共振成像和组织学检查皮质、海马体和小脑的神经退行性变。在AIM 3中，我们将整合纵向多对比MRI数据和中央框架中的组织学数据，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死亡受体的小鼠的HI损伤。我们还将在这个模型中检查Necrostatin的神经保护作用。我们期望该项目能提供损伤的时间进程和区域易感性的详细地图，扩展我们对小鼠模型中病理和诊断标记物之间关系的知识，并阐明HI损伤的机制和潜在的治疗方法。本项目开发的这些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.