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

基于定量 MRI 的阿尔茨海默病脑氧代谢

• 批准号: 10736489
• 负责人: GLORIA Chia-Yi CHIANG
• 金额: $ 83.54万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736489
• 关键词: Age; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease therapeutic; Amyloid beta-Protein; Apolipoprotein E; Assessment tool; Astrocytes; Biological Markers; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Trials; Cognitive; Data; Dementia; Deposition; Diagnosis; Disease Progression; Elderly; Enrollment; Fingerprint; Glucose; Glycolysis; Half-Life; Health; Image; Imaging Device; Imaging Techniques; Impaired cognition; Impairment; Injections; Iron; Learning; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Metabolic; Metabolic dysfunction; Metabolism; Microglia; Mission; Mitochondria; Modeling; Monitor; Nerve Degeneration; Neurofibrillary Tangles; Neurons; Noise; Outcomes Research; Oxidative Phosphorylation; Oxygen; Patient Monitoring; Patients; Pattern; Personal Satisfaction; Phase; Plasma; Positron-Emission Tomography; Predisposition; Preparation; Process; Property; Public Health; Radioactive Tracers; Radiochemistry; Research; Research Support; Resolution; Senile Plaques; Signal Transduction; Site; Speed; Staging; Techniques; Testing; Therapeutic Trials; Tissues; Work; abeta deposition; aged; arterial spin labeling; blood oxygen level dependent; cognitive testing; computerized data processing; cost; data acquisition; denoising; efficacy evaluation; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; follow-up; glucose uptake; gray matter; imaging study; improved; insight; metabolic imaging; metabolic rate; mild cognitive impairment; neuronal metabolism; non-invasive imaging; novel; prospective; radioligand; reconstruction; recruit; sex; standard of care; tool; treatment response

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.

项目摘要 阿尔茨海默氏病（AD）是痴呆症的最常见原因。当前的临床标准护理 评估AD代谢功能障碍的是18F氟脱氧葡萄糖（FDG）极性发射断层扫描（PET）， 基于颞叶型失去代谢模式。但是，1）宠物是不切实际的 评估工具，因为它需要注入放射性示踪剂，很昂贵，并且空间较差 与MRI相比，分辨率和可用性； 2）FDG-PET可能不是对神经元的准确测量 代谢，因为FDG信号还可以反映小胶质细胞和星形胶质细胞的葡萄糖吸收，以用于糖酵解 作为神经元氧化物磷酸化的葡萄糖摄取。氧的大脑代谢率（CMRO2）， 反映神经元线粒体中氧化磷酸化的可能会更直接地测量异常 MCI和AD患者可见代谢。此外，一种基于MRI的工具，用于绘制神经元代谢 将允许在临床和治疗试验中进行纵向监测。因此，这个目的 建议是开发和优化基于MR的CMRO2映射技术。 AIM 1将是开发一个多 回声梯度回声采集，与动脉自旋标记集成以构建氧气提取分数， 脑血流和CMRO2图绘制稀疏指纹图。 AIM 2将调查此cmro2是否 映射证明了区域相关性与包括A，TAU，包括A，TAU的衡量标准相关 和FDG缺乏代谢，这是2018年Nia-Alzheimer协会研究的“ ATN”阶段 框架。 AIM 3将研究我们的CMRO2映射在预测纵向灰质中的值 退化和认知能力下降。如果成功，该建议将发展并验证无创， 基于MR的定量工具，用于诊断和纵向评估AD中的脑缺乏代谢。