Assessment of Brain Oxygen Consumption in Neonates using MRI

项目摘要/摘要 阿尔茨海默病(AD)是老年人痴呆症的主要原因，是一种毁灭性的疾病 在后期的治疗中，结果令人失望。为了能够开发出有效的 在疾病的早期阶段进行治疗，需要敏感的生物标记物来早期发现 与淀粉样变病理无关(和互补)的神经退行性变。生理生物标记物可以 在这一过程中发挥重要作用。 家长奖R01NS109029专注于开发一种新的磁共振成像技术，用于 人脑氧摄取分数(OEF)和脑氧代谢率(CMRO2)的测定 新生儿作为新生儿窒息所致缺氧缺血性损伤的生物标志物。由于脑氧量 消耗是组织活力和大脑功能的一个关键标志，它也可以是一个重要的 神经退行性变中的生物标志物。先前使用正电子发射断层扫描(PET)技术的研究 已经显示出阿尔茨海默病患者大脑新陈代谢降低。然而，PET方法测量大脑新陈代谢 需要注射放射性示踪剂，因此不适合在临床试验中进行大规模筛查。 因此，在不使用外源性示踪剂的情况下，测量局部脑代谢的一种经济有效的mri技术是 希望促进利用脑代谢作为AD的早期生物标志物。 在这份补充资料中，我们建议并申请资金，以获得OEF和CMRO2在 通过对20名轻度认知障碍(MCI)患者和20名正常老年人的研究，发现阿尔茨海默病(AD) 受试者使用在相位对比下的加速T2弛豫(aTRU-PC)MRI技术 家长奖。我们的目标是验证这样一种假设，即大脑的氧气消耗是可以测量的 用我们的新技术对一个标准的核磁共振成像在不到5分钟的时间里，可以提供实用和性价比 老年人认知功能减退的生物标志物。具体来说，我们将比较OEF和CMRO2的值 并评估它们与认知表现的关系(总体认知和 认知领域)、疾病严重程度(临床痴呆评分，CDR)、血管危险因素(高血压、 高胆固醇血症、糖尿病、吸烟和肥胖)和其他影像和血液生物标志物(白质 高信号、糖化血红蛋白、同型半胱氨酸、低密度脂蛋白和高密度脂蛋白)。作为探索性分析，AD病理标志物 将从血浆中测量β淀粉样蛋白的含量，它们与OEF和CMRO2的关系也将是 评估过了。虽然有限的样本量不会对MCI和AD得出决定性的结果，但这一试点 研究将使我们能够获得第一个初步数据集，以判断更大规模研究的可行性，我们将 通过R01机制申请资金。

Project Summary/Abstract Alzheimer's disease (AD), the leading cause of dementia in older individuals, is a devastating disease for which treatment in later stages has yielded disappointing outcomes. In order to be able to develop effective treatments in earlier stages of the disease, there is a need for sensitive biomarkers that can detect early neurodegeneration independent of (and complementary to) amyloid pathology. Physiological biomarkers can play an important role in this process. The parent award, R01NS109029, focuses on the development of a novel MR imaging technique for the measurement of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in human neonates as a biomarker of hypoxic ischemic injuries due to birth asphyxia. Since cerebral oxygen consumption represents a key marker for tissue viability and brain function, it can also be an important biomarker in neurodegeneration. Previous studies using Positron Emission Tomography (PET) techniques have demonstrated reduced brain metabolism in AD. However, the PET methods to measure brain metabolism requires the injection of radioactive tracers and thus is not suitable for large-scale screening in clinical trials. Therefore, a cost-effective MRI technique to measure regional brain metabolism without exogenous tracers is desired to facilitate the utilization of brain metabolism as an early biomarker of AD. In this supplement, we propose and request funds to obtain quantitative maps of OEF and CMRO2 in Alzheimer's disease (AD) by studying 20 mild cognitive impairment (MCI) patients and 20 normal elderly subjects using the accelerated T2-Relaxation-Under-Phase-Contrast (aTRU-PC) MRI technique developed in the parent award. We aim to test the hypothesis that the brain's oxygen consumption, which can be measured with our novel techniques on a standard MRI in less than 5 minutes, can provide a practical and cost-effective biomarker of cognitive decline in elderly individuals. Specifically, we will compare the OEF and CMRO2 values between the two groups, and also evaluate their association with cognitive performance (overall cognition and cognitive domains), disease severity (Clinical-Dementia-Rating, CDR), vascular risk factors (hypertension, hypercholesterolemia, diabetes, smoking and obesity) and other imaging and blood biomarkers (white-matter hyperintensities, HbA1C, homocysteine, LDL, and HDL). As an exploratory analysis, AD pathological markers of beta-amyloid will be measured from plasma and their associations with OEF and CMRO2 will also be assessed. While the limited sample size will not allow conclusive results with respect to MCI and AD, this pilot study will allow us to get a first preliminary data set to judge the feasibility of a larger study for which we will request funding through the R01 mechanism.