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

项目摘要 阿尔茨海默病（AD）是痴呆症最常见的原因。目前的临床标准治疗 评估AD中的代谢功能障碍是18F-氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）， 基于颞顶代谢低下的模式然而，1）PET作为纵向测量是不切实际的。 评估工具，因为它需要注入放射性示踪剂，是昂贵的，并具有较差的空间 与MRI相比，FDG-PET的分辨率和可用性; 2）FDG-PET可能不是神经元功能的准确测量 因为FDG信号也可以反映小胶质细胞和星形胶质细胞对糖酵解的葡萄糖摄取， 作为葡萄糖摄取的氧化磷酸化神经元。脑氧代谢率（CMRO 2）， 反映了神经元线粒体中的氧化磷酸化，可以更直接地测量异常的 在MCI和AD患者中观察到的代谢。此外，基于MRI的神经元代谢映射工具 将允许在临床和治疗试验中进行纵向监测。因此，这一目标 建议是开发和优化基于MR的CMRO 2映射技术。目标1是建立一个多- 回波梯度回波采集，结合动脉自旋标记构建氧提取分数， 脑血流量和使用稀疏指纹的CMRO 2图。Aim 2将调查该CMRO 2是否 作图显示了与AD病理学的成熟测量的区域相关性，所述AD病理学包括A β，tau， 和FDG低代谢，根据2018年NIA-Alzheimer's Association研究的AD的“ATN”阶段 框架.目的3将研究我们的CMRO 2映射在预测纵向灰质中的价值 退化和认知能力下降。如果成功的话，这项提议将开发和验证一种非侵入性的， 定量MR为基础的工具，诊断和纵向评估脑代谢低下的AD。

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.