Molecular MRI of Brain Metabolism Enabled by Long-Lived Spin States

长寿命自旋态促进脑代谢的分子 MRI

基本信息

批准号：
10007222
负责人：
Thomas Theis
金额：
$ 80.74万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-06-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10007222
关键词：
Acetates Animals Antibiotics Antioxidants Area Ascorbic Acid BRAIN initiative Biochemical Biological Brain Brain Diseases Brain Mapping Brain imaging Chemicals Citric Acid Cycle Complex Coupling Development Diagnostic Disease Emerging Technologies Energy Metabolism Energy-Generating Resources Engineering Exhibits Glioblastoma Goals Health Homeostasis Hospitals Hour Human Hypoxia Image Individual Injectable Injections Kinetics Life Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Malignant neoplasm of brain Maps Metabolic Metabolic Pathway Metabolism Metronidazole Modality Molecular Monitor Nervous System Physiology Neurophysiology - biologic function Niacinamide Nicotinamide adenine dinucleotide Oxidation-Reduction Pathway interactions Penetration Pharmaceutical Preparations Play Population Positron-Emission Tomography Preparation Property Public Health Pyruvate Pyruvate Metabolism Pathway Radioactive Tracers Rattus Reaction Reporting Research Research Personnel Resolution Role Scanning Signal Transduction Signaling Molecule Spatial Distribution Spectrum Analysis Speed Techniques Technology Test Result Three-Dimensional Imaging Time Tissues Vitamins antibiotic tolerance aqueous ascorbate base brain cell brain metabolism cost cost efficient design imager imaging approach imaging capabilities imaging modality in vivo insight metabolic imaging molecular imaging neural circuit neuroimaging new technology next generation novel optical imaging patient population point of care preservation programs quantum sensor single photon emission computed tomography spectroscopic imaging technology development tomography tool uptake

项目摘要

Molecular MRI of Brain Metabolism enabled by Long-Lived Spin States Abstract: Brain function is regulated by molecular signaling and metabolism, however our ability to track metabolic transformations of individual metabolites deep in the brain pales compared to their central relevance to life. It is our goal to establish technology for tomographic mapping of metabolites and their metabolic pathways directly in the brain. Specifically, we aim to map metabolic turnover of13C2-pyruvate, ethyl-13C2-pyruvate, 13C2-Vitamin C, 15N-Vitamin B3, 15N3-Metronidazole (a well-tolerated antibiotic and potential hypoxia probe), and 13C2-Acetate. All of these markers play critical roles in brain metabolism: pyruvate is a key entry point to energy metabolism and the tricarboxylic acid (TCA) cycle; Vitamin C (ascorbate) is a vital antioxidant molecule in the brain; Vitamin B3 (Nicotinamide) is a precursor to NAD (nicotinamide adenine dinucleotide), a key regulator of cellular and organismal homeostasis and redox-status; metronidazole is an antibiotic that undergoes quick turnover in hypoxic tissue and promises to be a very sensitive hypoxia sensor; Finally, acetate acts as an alternative energy source for the brain and exhibits rapid and differential uptake and metabolism in, for example, glioblastoma multiform, a deadly brain cancer. From a technological perspective, each of the proposed molecules can carry long-lived hyperpolarization in NMR-silent, yet RF-accessible quantum states. This property is important because it allows for very long-lived MRI signals from these molecules that can directly report on chemical transformations via changes in chemical shift and the scalar coupling network. This ability will allow us to assess kinetics and spatial distribution of reaction pathways of metabolites at low concentration with sub-second resolution. We have already demonstrated the fundamental physical principles: i.e. lifetime extension of NMR signals by long-lived spin states. This proposal transforms our advances into practical, general, and affordable technology which will give us unprecedented insights into the metabolic basis of brain function with clear potential for scanning broad patient populations.

长寿命自旋态促进脑代谢的分子 MRI 抽象的：大脑功能受到分子信号和代谢的调节，但是我们跟踪代谢的能力大脑深处单个代谢物的转变与它们与生命的核心相关性相比显得相形见绌。这是我们的目标是直接建立代谢物及其代谢途径的断层成像技术在大脑中。具体来说，我们的目标是绘制 13C2-丙酮酸、13C2-丙酮酸乙酯、13C2-维生素 C、 15N-维生素 B3、15N3-甲硝唑（一种耐受性良好的抗生素和潜在的缺氧探针）和 13C2-醋酸盐。全部这些标记物在大脑代谢中发挥着关键作用：丙酮酸是能量代谢的关键入口点，三羧酸（TCA）循环；维生素 C（抗坏血酸）是大脑中重要的抗氧化分子；维生素B3 （烟酰胺）是 NAD（烟酰胺腺嘌呤二核苷酸）的前体，NAD 是细胞和机体稳态和氧化还原状态；甲硝唑是一种在体内快速周转的抗生素缺氧组织，有望成为非常灵敏的缺氧传感器；最后，醋酸盐作为替代能源大脑的来源，并在例如胶质母细胞瘤中表现出快速且差异化的吸收和代谢多种形式，一种致命的脑癌。从技术角度来看，每个提出的分子都可以携带长寿命的超极化处于核磁共振沉默但射频可访问的量子态。该属性很重要，因为它可以实现非常长的寿命来自这些分子的 MRI 信号可以通过化学变化直接报告化学转变位移和标量耦合网络。这种能力将使我们能够评估反应的动力学和空间分布亚秒级分辨率的低浓度代谢物途径。我们已经展示了基本物理原理：即通过长寿命的自旋态延长 NMR 信号的寿命。这个提议将我们的进步转化为实用、通用且负担得起的技术，这将为我们带来前所未有的对大脑功能代谢基础的深入了解，具有扫描广泛患者群体的明显潜力。