Assessment of brain oxygen consumption in neonates using MRI

项目摘要/摘要 出生窒息，指的是由于产中并发症导致的缺氧，每1000人中就有1到6人发生窒息。 活着足月出生。它会导致缺氧性脑损伤，是导致新生儿死亡和 长期残疾。需要非侵入性生物标记物来评估缺氧造成的程度 脑部受伤。然而，到目前为止，还缺乏可靠的生物标记物来预测临床结果。传统型 解剖MRI序列(如T1和T2)可以显示损伤引起的结构性损害，但它们对 检测细微损伤和神经异常是有限的。因此，这个项目的目标是开发和 评估与新生儿脑氧利用相关的新生物标志物的临床应用 氧代谢率(CMRO2)及其关键成分氧提取率(OEF)。 脑氧耗是新生儿窒息病理过程中的中心环节。 然而，目前还没有实用的技术来评估人类的脑氧代谢。 新生儿。已用于成人CMRO2成像的正电子发射断层扫描(PET)方法 由于程序的复杂性和辐射问题，不容易在新生儿人群中使用。 在这个项目中，我们将开发一种基于MR的技术来测量OEF和CMRO2，而不使用任何 外源性造影剂。OEF和CMRO2定量的一个关键成分是静脉氧气 饱和度。在这个项目中，我们将设计一种新的脉冲序列，加速T2-相下弛豫- 对比剂(aTRU-PC)，以区域特有的方式测量静脉氧合，OEF和 CMRO2将被量化。 该项目由技术开发(目标1)、验证(目标2)和初始三个逻辑目标组成 新生儿缺氧缺血性脑病(HIE)的临床应用示范(目标3)。目标1 将专注于开发用于测量区域静脉氧合的aTRU-PC序列 以及一项多点评估，以检查该方法的重复性和可扩展性 建议的技术。目标2将重点放在新生儿MRI氧合技术的有效性上 小猪模型。目的3将重点评估OEF和CMRO2作为功能性生物标志物的临床应用价值。 新生儿缺氧缺血性脑病。我们假设OEF和CMRO2将与HIE的严重程度和短期 结果。 影响：该项目完成后，我们将能够提供新生儿神经成像 社区使用了一种新的MRI技术来定量评估脑氧利用情况，并将 证明了其在HIE中的临床应用价值。

Project Summary/Abstract Birth asphyxia, referring to oxygen deprivation due to intrapartum complications, occurs in 1 to 6 per 1000 live full-term birth. It causes hypoxic brain injuries and is one of the leading reasons of neonatal death and long-term disabilities. Non-invasive biomarkers are needed to assess the extent to which hypoxia has caused brain injury. To date, however, reliable biomarkers to predict clinical outcomes are lacking. Conventional anatomic MRI sequences (e.g. T1 and T2) can show structural lesions due to injury, but their sensitivity in detecting subtle injury and neural abnormality is limited. Therefore, the goal of this project is to develop and evaluate the clinical utility of novel biomarkers related to neonatal brain’s oxygen utilization, including cerebral metabolic rate of oxygen (CMRO2) and its key component, oxygen extraction rate (OEF). Cerebral oxygen consumption is a central piece in the pathological process underlying birth asphyxia. However, at present, there exist no practical techniques to assess cerebral oxygen metabolism in human neonates. Positron Emission Tomography (PET) methods that have been used for adult CMRO2 imaging cannot be easily used in neonatal population due to the complexity of the procedures and radiation concerns. In this project, we will develop a MR based technique to measure OEF and CMRO2 without using any exogenous contrast agent. A critical component in OEF and CMRO2 quantification is venous oxygen saturation. In this project, we will devise a novel pulse sequence, accelerated T2-Relaxation-Under-Phase- Contrast (aTRU-PC), to measure venous oxygenation in a region-specific manner, from which OEF and CMRO2 will be quantified. The project consists of three logical aims of technical development (Aim 1), validation (Aim 2), and initial demonstration of clinical utility in neonatal patients with hypoxic ischemic encephalopathy (HIE) (Aim 3). Aim 1 will focus on the development of the aTRU-PC sequence for the measurement of regional venous oxygenation in healthy neonates as well as a multi-site evaluation to examine the reproducibility and scalability of the proposed technique. Aim 2 will focus on the validation of the proposed MRI oxygenation technique in newborn piglet model. Aim 3 will focus on evaluating the clinical utility of OEF and CMRO2 as a functional biomarker in neonatal HIE. We hypothesize that OEF and CMRO2 will be associated with HIE severity and the short-term outcomes. Impact: Upon the completion of this project, we will be able to provide the neonatal neuroimaging community with a new MRI technique for quantitative assessment of brain oxygen utilization and will have demonstrated its clinical utility in HIE.