Assessment of brain oxygen consumption in neonates using MRI

项目概要/摘要 出生窒息，指的是由于分娩并发症而导致的缺氧，发生在每1000人中有1至6人 足月分娩。它导致缺氧性脑损伤，是新生儿死亡的主要原因之一， 长期残疾。需要非侵入性生物标志物来评估缺氧引起的程度 脑损伤然而，迄今为止，缺乏可靠的生物标志物来预测临床结果。常规 解剖MRI序列（例如T1和T2）可以显示由于损伤引起的结构性病变，但它们在 检测细微损伤和神经异常是有限的。因此，该项目的目标是开发和 评估与新生儿脑氧利用相关的新型生物标志物的临床效用，包括脑氧代谢， 氧代谢率（CMRO 2）及其关键成分氧提取率（OEF）。 脑耗氧量是新生儿窒息病理过程的核心。 然而，目前还没有实用的技术来评估人的脑氧代谢 新生儿已用于成人CMRO 2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，不能容易地用于新生儿群体。 在这个项目中，我们将开发一种基于MR的技术来测量OEF和CMRO 2，而不使用任何 外源性造影剂OEF和CMRO 2定量的关键组成部分是静脉氧 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-弛豫下相， 造影剂（aTRU-PC），以特定区域的方式测量静脉氧合，从中确定OEF和 CMRO 2将被量化。 该项目包括三个逻辑目标：技术开发（目标1）、验证（目标2）和初始化（目标3）。 证明在新生儿缺氧缺血性脑病（HIE）患者中的临床实用性（目的3）。要求1 将重点开发用于测量局部静脉氧合的aTRU-PC序列 在健康新生儿中进行，并进行多中心评价，以检查 提出的技术。目标2将集中于在新生儿中验证所提出的MRI氧合技术 小猪模型目标3将重点评估OEF和CMRO 2作为功能性生物标志物在 新生儿HIE我们假设OEF和CMRO 2与HIE的严重程度和短期预后有关。 结果。 影响：该项目完成后，我们将能够提供新生儿神经影像学 一个新的MRI技术定量评估脑氧利用的社区，并将有 证明了其在HIE中的临床实用性。

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.