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

长寿命自旋态实现脑代谢的分子MRI 摘要： 大脑功能受分子信号和代谢的调节，然而我们跟踪代谢的能力 与它们与生命的核心相关性相比，大脑深处单个代谢物的转化相形见绌。是 我们的目标是建立直接绘制代谢物及其代谢途径的断层扫描技术 在大脑中。具体来说，我们的目标是绘制13 C2-丙酮酸，乙基-13 C2-丙酮酸，13 C2-维生素C， 15 N-维生素B3、15 N3-甲硝唑（一种耐受性良好的抗生素和潜在的缺氧探针）和13 C2-乙酸盐。所有 这些标志物在脑代谢中起着关键作用：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是细胞和免疫系统的关键调节因子。 生物体内平衡和氧化还原状态;甲硝唑是一种抗生素， 缺氧组织，并有望成为一个非常敏感的缺氧传感器;最后，乙酸作为一种替代能源 脑源，并在例如胶质母细胞瘤中表现出快速和差异性摄取和代谢 一种致命的脑癌 从技术的角度来看，每一个提出的分子都可以携带长寿命的超极化 在核磁共振沉默，但射频可访问的量子态。这个属性很重要，因为它允许非常长的寿命 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化。 移位和标量耦合网络。这种能力将使我们能够评估反应的动力学和空间分布 低浓度代谢物的代谢途径，分辨率低于秒级。我们已经展示了 基本物理原理：即通过长寿命自旋状态延长NMR信号的寿命。这项建议 将我们的进步转化为实用，通用和负担得起的技术，这将为我们提供前所未有的 深入了解大脑功能的代谢基础，具有扫描广泛患者人群的明确潜力。

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.