Imaging Neonatal Hypoxic Ischemic Injury

新生儿缺氧缺血性损伤的影像学

• 批准号: 10447137
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447137
• 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 婴儿缺血性缺血（HI）损害婴儿的白质和灰质，并引起明显的 死亡率和发病率。研究新生儿HI损伤的病理机制并感到满意 已建立并广泛使用了治疗，新生儿缺血性缺血性损伤的动物模型。在这个 项目，在组织微观结构和神经元活性上的新型体内磁共振成像将是 开发用于检查HI损伤的进展和新生儿治疗性低温的影响 鼠标模型。 在AIM 1中，我们将研究新型扩散MRI（DMRI）技术对组织微结构的敏感性 HI受伤引起的变化。初步结果表明，提出的成像技术可以更多 比传统的DMRI技术敏感地检测到轻度的脑损伤，并且不易混淆 常规DMRI信号的伪正规化。我们将使用组织学和电子显微镜 确定细胞和亚细胞结构变化的水平并相关定量测量 使用DMRI信号，并使用数值模拟来了解它们之间的关系。这 知识将用于优化成像协议，以检测新生儿HI之后的关键结构变化。 在AIM 2中，我们将使用锰增强的MRI（MEMRI）检查伤害。先前的研究表明 memri的对比反映了大脑中的神经元活性，并可以选择性地增强区域 新生儿HI后的凋亡和炎症。在此目标中，我们将研究Memri对丢失的敏感性 新生儿HI后神经元活性，凋亡和炎症。使用DMRI和MEMRI，我们将能够 检查新生儿HI后的广泛病理事件。 体温过低是新生儿HI的新生儿的标准护理，但其保护机制不是 清楚地理解。已经假定体温过低会减少细胞肿胀，炎症和血管生成 水肿，并且可能会延迟伪正归于过程。在AIM 3中，这些技术在前两个 然后，AIMS将应用于表征用体温过低治疗的小鼠中的HI损伤以定量 表征其作用并阐明其神经保护机制。 我们希望该项目能够扩展有关病理与诊断之间关系的知识 该小鼠模型中的标记，并阐明了HI损伤和治疗性体温过低的机制。这 该项目中开发的信息和技术将有助于设计干预的有效策略 并使用此或类似模型监测研究中的治疗反应。