Assessment of Brain Oxygen Consumption in Neonates using MRI

使用 MRI 评估新生儿脑耗氧量

• 批准号: 10119483
• 负责人: Peiying Liu
• 金额: $ 9.58万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10119483
• 关键词: Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid beta-Protein; Asphyxia Neonatorum; Award; Biological Markers; Blood; Brain; Cerebrum; Clinical; Clinical Trials; Cognition; Cognitive; Data Set; Dementia; Development; Diabetes Mellitus; Disease; Elderly; Funding; Glycosylated hemoglobin A; High Density Lipoproteins; Homocysteine; Human; Hypertension; Hypoxia; Image; Imaging Techniques; Impaired cognition; Individual; Injections; Low-Density Lipoproteins; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Nerve Degeneration; Obesity; Outcome; Oxygen; Oxygen Consumption; Parents; Pathologic; Patients; Phase; Physiological; Pilot Projects; Plasma; Play; Positron-Emission Tomography; Process; Radioactive Tracers; Relaxation; Research Project Grants; Role; Sample Size; Severity of illness; Smoking; Techniques; Testing; Tissue Viability; Tracer; White Matter Hyperintensity; amyloid pathology; brain metabolism; brain tissue; cognitive performance; cost effective; early detection biomarkers; effective therapy; hypercholesterolemia; ischemic injury; metabolic rate; mild cognitive impairment; neonate; novel; screening; vascular risk factor

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.

项目总结/摘要 阿尔茨海默病（AD）是老年人痴呆的主要原因，是一种对老年人具有毁灭性影响的疾病。 后期的治疗结果令人失望。为了能够有效地开发 为了在疾病的早期阶段进行治疗，需要敏感的生物标志物， 神经变性独立于（和补充）淀粉样蛋白病理。生理生物标记物可以 在这一过程中发挥重要作用。 母奖R 01 NS 109029专注于开发一种新型MR成像技术， 人氧摄取分数和脑氧代谢率的测定 新生儿缺氧缺血性损伤的生物标志物由于出生窒息。因为脑氧 消耗代表组织活力和脑功能的关键标志，它也可以是重要的 神经变性的生物标志物。使用正电子发射断层扫描（PET）技术的既往研究 已经证明了AD患者的脑代谢降低。然而，PET测量大脑代谢的方法 需要注射放射性示踪剂，因此不适合于临床试验中的大规模筛选。 因此，一种无外源性示踪剂的低成本MRI技术来测量局部脑代谢， 期望促进脑代谢作为AD的早期生物标志物的利用。 在这份补充文件中，我们建议并要求拨款，以取得 通过对20例轻度认知功能障碍（MCI）患者和20例正常老年人的研究， 受试者使用开发的加速T2-弛豫-相衬下（aTRU-PC）MRI技术， 家长奖。我们的目标是检验大脑的耗氧量这一假设， 我们的新技术在标准MRI上不到5分钟，可以提供实用且具有成本效益的 老年人认知能力下降的生物标志物。具体而言，我们将比较OEF和CMRO 2值 两组之间，并评估其与认知表现（整体认知和 认知领域），疾病严重程度（临床痴呆分级，CDR），血管危险因素（高血压， 高胆固醇血症、糖尿病、吸烟和肥胖）和其它成像和血液生物标志物（白质 高强度、HbA 1C、同型半胱氨酸、LDL和HDL）。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，并将其与OEF和CMRO 2的相关性进行分析。 评估。虽然有限的样本量将不允许关于MCI和AD的结论性结果， 这项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， 通过R 01机制申请资金。