Quantification of brain metabolic rate in neonates using MRI

使用 MRI 量化新生儿脑代谢率

• 批准号: 8989580
• 负责人: Peiying Liu
• 金额: $ 21.28万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8989580
• 关键词: Quantification; brain; metabolic; rate; neonates

DESCRIPTION (provided by applicant): The goal of the present project is to develop a clinically practical technique to quantify oxygen utilization in neonatal brain. Oxidative metabolism is the primary form of energy production in the human brain. Therefore, cerebral metabolic rate of oxygen (CMRO2) is an important index of brain function and tissue viability. Neonatal stage is particularly susceptible to disruptions in oxygen supply and metabolism, for example in the case of hypoxic ischemic encephalopathy (HIE) which is a consequence of oxygen deprivation in neonates due to birth asphyxia. Therefore, the availability of a non-invasive technique to determine CMRO2 in neonates may find immediate application in the diagnosis of HIE as well as in the treatment monitoring of HIE using hypothermia, which aim to reduce the brain's metabolic rate and preserve ATP. At present, there exist no practical techniques to determine CMRO2 in human neonates, because the conventional method of Positron Emission Tomography (PET) is not applicable due to radiation concerns. In this project, we will develop MR based techniques to measure CMRO2 in neonates. Our goal is to provide the clinical community a CMRO2 tool for neonatal applications that is completely non-invasive (no exogenous agent), rapid (<5 min of scan time), and can be performed on a standard 3 Tesla MRI. The PI's previous work has demonstrated that this goal is feasible in adult brain. Thus, the present project will benefit from our extensive experiences of developing this technique in adults. We have two Specific Aims. Aim 1 will focus on in vivo studies of developing MR imaging protocols for the measurement of global CMRO2 in human neonatal subjects. We will conduct separate sub-studies to optimize several technical aspects of the venous oxygenation (TRUST MRI) and blood flow (phase-contrast MRI) techniques, including developing an automated, individualized labeling-slab positioning, comparison between triggered and non-triggered phase- contrast MRI, and determining optimal spatial resolution for neonatal imaging. Aim 2 will focus on in vitro studies of neonatal blood T2 relaxometry, conducted on fresh cord blood of human neonates. This will allow us to obtain a calibration plot specifying blood T2 dependence on oxygenation, which is needed for calibrating the in vivo data. We clarify that, once the calibratio plot is established, it can be used for all future in vivo data, not just data collected in Aim 1. he neonatal T2 relaxometry will also provide important reference for many other MRI pulse sequences in neonates beyond the techniques in the proposed study, such as T2-prepared angiogram and susceptibility weighted imaging (SWI). Upon finishing this project, we will be able to provide researchers and clinicians with a set of MRI techniques for CMRO2 measurements that are ready for immediate applications in brain development and neonatal brain disorders.

描述（由申请人提供）：本项目的目标是开发一种临床实用的技术来量化新生儿大脑中的氧利用率。氧化代谢是人类大脑中能量产生的主要形式。因此，脑氧代谢率（CMRO 2）是脑功能和组织活力的重要指标。新生儿阶段特别容易受到氧供应和代谢中断的影响，例如在缺氧缺血性脑病（HIE）的情况下，缺氧缺血性脑病（HIE）是新生儿由于出生窒息而缺氧的结果。因此，在新生儿中确定CMRO2的非侵入性技术的可用性可以立即应用于HIE的诊断以及使用低温的HIE的治疗监测，其目的是降低大脑的代谢率并保存ATP。 目前，还没有实用的技术来确定人类新生儿中的CMRO2，因为常规的正电子发射断层扫描（PET）方法由于辐射问题而不适用。在这个项目中，我们将开发基于MR的技术来测量新生儿的CMRO2。我们的目标是为临床社区提供一种用于新生儿应用的CMRO2工具，该工具完全无创（无外源性试剂），快速（扫描时间<5分钟），并且可以在标准3特斯拉MRI上进行。PI先前的工作已经证明，这一目标在成人大脑中是可行的。因此，本项目将受益于我们在成人中开发这种技术的丰富经验。我们有两个具体目标。目标1将侧重于开发用于测量人类新生儿受试者的全局CMRO2的MR成像方案的体内研究。我们将进行单独的子研究，以优化静脉氧合（TRUST MRI）和血流（相位对比MRI）技术的几个技术方面，包括开发自动化、个性化的标记板定位、比较触发和非触发相位对比MRI，以及确定新生儿成像的最佳空间分辨率。目的2将集中在新生儿血液T2弛豫测定法的体外研究，对人类新生儿的新鲜脐带血进行。这将允许我们获得指定血液T2对氧合的依赖性的校准图，这是校准体内数据所需的。我们澄清，一旦建立校准图，它可以用于所有未来的体内数据，而不仅仅是目标1中收集的数据。新生儿T2弛豫测量还将为拟议研究中技术之外的新生儿许多其他MRI脉冲序列提供重要参考，例如T2准备血管造影和磁敏感加权成像（SWI）。 完成这个项目后，我们将能够为研究人员和临床医生提供一套用于CMRO2测量的MRI技术，这些技术可以立即应用于大脑发育和新生儿大脑疾病。