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.

长寿命旋转态实现了脑代谢的分子MRI 抽象的：大脑功能受分子信号传导和代谢调节，但是我们追踪代谢的能力与生命的核心相关性相比，大脑中各个代谢产物的转变。这是我们的目标是直接直接用于代谢物及其代谢途径的技术在大脑中。具体而言，我们旨在绘制13C2-丙酮酸，乙基13c2-丙酮酸，13c2-Vitamin C的代谢周转率， 15N-维生素B3，15n3-甲酮唑（一种耐受良好的抗生素和潜在的低氧探针）和13c2-乙酸盐。全部这些标志物在大脑代谢中起着关键作用：丙酮酸是能量代谢和三羧酸（TCA）周期；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，这是细胞和细胞的关键调节剂有机体稳态和氧化还原状态；甲硝唑是一种抗生素，经历了快速营业额缺氧组织，并有望成为非常敏感的缺氧传感器。最后，醋酸盐充当替代能量大脑的来源，并在例如胶质母细胞瘤中表现出快速和差异的摄取和代谢多形，致命的脑癌。从技术的角度来看，每个提出的分子都可以携带长寿命超极化在NMR-SiLent但可访问RF的量子状态中。该属性很重要，因为它允许长寿这些分子的MRI信号可以通过化学变化直接报告化学转化 Shift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在低浓度下分辨率下代谢物的途径。我们已经证明了基本物理原理：即长寿命旋转状态对NMR信号的寿命扩展。这个建议将我们的进步转变为实用，一般和负担得起的技术，这将使我们前所未有洞悉大脑功能的代谢基础，具有明显的扫描广泛患者人群的潜力。