Quantitative MRI-based cerebral oxygen metabolism in Alzheimer's disease

项目摘要 阿尔茨海默病(AD)是导致痴呆症的最常见原因。目前的临床护理标准 评价AD患者代谢功能障碍的方法是18F-脱氧葡萄糖(FDG)正电子发射断层扫描(PET)。 基于低新陈代谢的顶叶模式。然而，1)PET作为纵向扫描是不切实际的 评估工具，因为它需要注射放射性示踪剂，价格昂贵，空间较差 分辨率和可用性与MRI相比；以及2)FDG-PET可能不是神经元的准确测量 代谢，因为FDG信号也可以反映小胶质细胞和星形胶质细胞摄取葡萄糖进行糖酵解 作为神经元氧化磷酸化的葡萄糖摄取。脑氧代谢率(CMRO2)， 反映神经元线粒体氧化磷酸化，可能更直接地衡量异常 代谢可见于MCI和AD患者。此外，一种基于MRI的神经元新陈代谢测绘工具 将允许在临床和治疗试验中进行纵向监测。因此，这样做的目的是 建议开发和优化一种基于MR的CMRO2标测技术。目标1将是开发一种多- 回声梯度回声采集，与动脉自旋标记相结合，构建氧提取分数， 脑血流量，并使用稀疏指纹绘制CMRO2图。AIM 2将调查CMRO2 测绘显示了与AD病理指标的区域相关性，包括A、tau、 和FDG代谢低下，根据2018年NIA-阿尔茨海默氏症协会的研究，AD的“ATN”阶段 框架。目标3将研究我们的CMRO2图在预测纵向灰质中的价值 退化和认知衰退。如果成功，这项提案将开发并验证一种非侵入性、 基于磁共振的定量工具诊断和纵向评估阿尔茨海默病患者的大脑低代谢。

Project Summary Alzheimer's disease (AD) is the most common cause of dementia. Current clinical standard-of-care for assessing metabolic dysfunction in AD is 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), based on a temporoparietal pattern of hypometabolism. However, 1) PET is impractical as a longitudinal assessment tool because it requires injection of a radioactive tracer, is expensive, and has poorer spatial resolution and availability compared to MRI; and 2) FDG-PET may not be an accurate measure of neuronal metabolism, because FDG signal can reflect glucose uptake by microglia and astrocytes for glycolysis, as well as glucose uptake for oxidative phosphorylation by neurons. The cerebral metabolic rate of oxygen (CMRO2), reflective of oxidative phosphorylation in neuronal mitochondria, may more directly measure the abnormal metabolism seen in patients with MCI and AD. Moreover, an MRI-based tool for mapping neuronal metabolism would allow for longitudinal monitoring both clinically and in therapeutic trials. Therefore, the objective of this proposal is to develop and optimize an MR-based CMRO2 mapping technique. Aim 1 will be to develop a multi- echo gradient echo acquisition, integrated with arterial spin labeling to construct oxygen extraction fraction, cerebral blood flow, and CMRO2 maps using sparsity fingerprinting. Aim 2 will investigate whether this CMRO2 mapping demonstrates regional correlation with well-established measures of AD pathology, including A, tau, and FDG hypometabolism, the “ATN” stages of AD per the 2018 NIA-Alzheimer's Association research framework. Aim 3 will investigate the value of our CMRO2 mapping in predicting longitudinal gray matter degeneration and cognitive decline. If successful, this proposal will develop and validate a noninvasive, quantitative MR-based tool to diagnose and longitudinally assess cerebral hypometabolism in AD.