Imaging Neonatal Hypoxic Ischemic Injury

新生儿缺氧缺血性损伤的影像学

• 批准号: 10249146
• 负责人: FRANCES J NORTHINGTON
• 金额: $ 59.83万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-16 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249146
• 关键词: 3-Dimensional; Acute; Adult; Affect; Anatomy; Animal Model; Apoptosis; Brain; Brain Injuries; Calcium; Cell Death; Cells; Cellular Structures; Cessation of life; Clinic; Correlation Studies; Data; Developed Countries; Development; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Electron Microscopy; Event; Face; Future; Gliosis; Histologic; Histology; Hour; Hybrids; Hypoxia; Hypoxic-Ischemic Brain Injury; Image; Image Analysis; Imaging Techniques; Infant; Infant Care; Inflammation; Injury; Intervention; Knowledge; Light; Link; Magnetic Resonance Imaging; Manganese; Maps; Measurement; Measures; Microscopic; Modeling; Monitor; Morbidity - disease rate; Mus; Necrosis; Nerve Degeneration; Neurodevelopmental Disability; Neurological outcome; Neurons; Newborn Infant; Outcome; Pathogenesis; Pathologic; Pathology; Pattern; Physics; Process; Protocols documentation; Reporting; Research; Resolution; Scanning Electron Microscopy; Signal Transduction; Structure; Subcellular structure; Swelling; Techniques; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Time; Tissues; accurate diagnosis; base; cellular imaging; cellular pathology; critical period; design; diagnostic biomarker; gray matter; hypoxia neonatorum; hypoxic ischemic injury; in vivo; interest; ischemic injury; mortality; mouse model; natural hypothermia; neonatal brain; neonatal hypoxic-ischemic brain injury; neonatal mice; neuroimaging; neuron loss; non-invasive monitor; novel; novel imaging technique; pathology imaging; preservation; regenerative therapy; repaired; simulation; spatiotemporal; standard care; standard of care; treatment response; vasogenic edema; white matter

Abstract Hypoxic ischemic (HI) insult damages both 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 on tissue microstructure and neuronal activity will be developed to examine the progression of HI injury and the effects of therapeutic hypothermia in a neonatal mouse model. In aim 1, we will examine the sensitivity of novel diffusion MRI (dMRI) techniques to tissue microstructural changes caused by HI injury. Preliminary results have shown that the proposed imaging techniques can more sensitively detect mild brain injuries than conventional dMRI techniques and is less susceptible to confounding pseudo-normalization of conventional dMRI signals. We will use histology and electron microscopy to determine the levels of cellular and subcellular structural changes and correlate quantitative measurements with dMRI signals, and use numerical simulations to understand the relationships between them. The knowledge will be used to optimize the imaging protocols to detect key structural changes after neonatal HI. In aim 2, we will examine injury using manganese-enhanced MRI (MEMRI). Previous studies have shown that the MEMRI contrasts reflect neuronal activity in the brain and can selectively enhance regions with apoptosis and inflammation after neonatal HI. In this aim, we will examine the sensitivity of MEMRI to loss of neuronal activity, apoptosis, and inflammation after neonatal HI. With both dMRI and MEMRI, we will be able to examine a broad range of pathological events after neonatal HI. Hypothermia is the standard care for newborns with neonatal HI, but its protective mechanisms are not clearly understood. It has been assumed that hypothermia reduces cell swelling, inflammation, and vasogenic edema, and may delay the pseudo-normalization process. In aim 3, the techniques developed in the first two aims will then be applied to characterize HI injury in mice treated with hypothermia to quantitatively characterize its effects and elucidate its neuroprotective mechanisms. We expect the project to extend our knowledge on the relationships between pathology and diagnostic markers in this mouse model, and shed light on the mechanisms of HI injury and therapeutic hypothermia. 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.

抽象的 缺氧缺血（HI）损伤会损害婴儿的白质和灰质，并导致严重的 死亡率和发病率。探讨新生儿HI损伤的病理机制并寻找满意的结果 治疗方面，新生儿缺氧缺血性损伤的动物模型已建立并广泛应用。在这个 该项目将研究组织微观结构和神经元活动的新型体内磁共振成像 旨在检查新生儿 HI 损伤的进展以及低温治疗的效果 鼠标模型。 在目标 1 中，我们将检查新型扩散 MRI (dMRI) 技术对组织微观结构的敏感性 HI 损伤引起的变化。初步结果表明，所提出的成像技术可以更多地 与传统 dMRI 技术相比，可以灵敏地检测轻度脑损伤，并且不易受到混淆 传统 dMRI 信号的伪标准化。我们将使用组织学和电子显微镜来 确定细胞和亚细胞结构变化的水平并关联定量测量 dMRI 信号，并使用数值模拟来理解它们之间的关系。这 知识将用于优化成像方案，以检测新生儿 HI 后的关键结构变化。 在目标 2 中，我们将使用锰增强 MRI (MEMRI) 检查损伤情况。先前的研究表明 MEMRI 对比反映了大脑中的神经元活动，并且可以选择性地增强具有以下特征的区域： 新生儿 HI 后的细胞凋亡和炎症。为此，我们将检查 MEMRI 对丢失的敏感性 新生儿 HI 后的神经元活动、细胞凋亡和炎症。借助 dMRI 和 MEMRI，我们将能够 检查新生儿 HI 后的广泛病理事件。 低温治疗是新生儿 HI 新生儿的标准护理，但其保护机制并非如此 清楚地明白了。人们认为低温会减少细胞肿胀、炎症和血管生成 水肿，并可能延迟伪正常化过程。在目标 3 中，前两个目标中开发的技术 然后，目标将用于定量描述接受低温治疗的小鼠的 HI 损伤特征 描述其作用并阐明其神经保护机制。 我们希望该项目能够扩展我们对病理学和诊断之间关系的了解 小鼠模型中的标记物，并阐明了 HI 损伤和治疗性低温的机制。这 该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。