Novel MRS methods for measuring brain energetics and neurotransmitter cycling

用于测量大脑能量学和神经递质循环的新 MRS 方法

• 批准号: 8990476
• 负责人: Daniel M Spielman
• 金额: $ 20.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8990476
• 关键词: Acetates; Animal Model; Animals; Back; Brain; Carbon; Cell Cycle; Cell Nucleus; Citric Acid Cycle; Clinical; Complex; Coupled; Coupling; Data; Deposition; Detection; Development; Distal; Energy Metabolism; Eye; Family; Glucose; Glutamates; Glutamine; Goals; Health; Heating; Human; In Vitro; Infusion procedures; Label; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measurement; Measures; Mental disorders; Metabolic; Methods; Modeling; Neurons; Neurosciences; Neurotransmitters; Performance; Phase; Physiologic pulse; Protons; Rattus; Research; Scanning; Signal Transduction; Sum; System; Techniques; Time; Tissues; Translations; Tricarboxylic Acids; Universities; Water; Work; absorption; base; brain metabolism; human subject; in vivo; in vivo Model; interest; magnetic field; nervous system disorder; neuronal metabolism; novel; success

DESCRIPTION (provided by applicant): Understanding neuronal metabolism is critical for studies of brain function, and magnetic resonance spectroscopy (MRS) of infused 13C-labeled substrates is well established as the only noninvasive in-vivo technique capable of measuring glutamate neurotransmitter cycling and cell-specific neuroenergetics in both normal and diseased states. Using metabolic modeling, in vivo 13C MRS studies have successfully compared neuronal and glial energy metabolism, elucidated the linkage between neuroenergetics and neurotransmitter cycling, and identified altered brain metabolism in multiple neurological and psychiatric diseases. In vivo human studies, however, are technically challenging due to low sensitivity and complex overlapping spectra arising from J-coupling between 1H and 13C nuclei. Although the use of decoupling, a well-known NMR method to simplify spectra, has been critical to the success of in vivo studies, associated Specific Absorption Rate (SAR) limits currently restrict human studies to the occipital brain (distal to the highly heat-sensitive eyes) and to field strengths d 4T. As described in our preliminary data, we have developed a novel family of MRS pulse sequences that simultaneously generate both in-phase and anti-phase magnetization the sum of which result in a single peak, obviating the need for high-power decoupling. This presents a major new opportunity to significantly extend current in vivo human 13C MRS brain studies. The goal of this two-year technical development R21 project is to develop optimized these new 1H-13C MRS methods for the in vivo measurement of neuronal and glial TCA fluxes and glutamate/glutamine cycling rates. The focus is on ultra-high field (e7 T) indirect detection methods that maximize sensitivity in order t enable interrogating small tissue regions (~1 cc) throughout the human brain within acceptable scan times. The resulting pulse sequence(s) will be evaluated in vitro, in phantoms, and using a rat animal model, with the successful completion of the research plan producing the critical preliminary data needed to justify transitioning to human studies.

描述（由申请人提供）：理解神经元代谢对于脑功能研究至关重要，并且被注入13C标记的底物的磁共振光谱（MRS）是唯一能够测量谷氨酸型Neurotransmitter cyclansmitter cyclansmitter cyclansmitter cyclanss和细胞的神经细胞和特异性神经剂的唯一无创的病毒感受器技术。使用代谢建模，体内13C MRS研究成功地比较了神经元和神经胶质能代谢，阐明了神经生能与神经递质循环之间的联系，并确定了多种神经和精神疾病的脑代谢改变。 然而，由于1H和13C核之间J偶联引起的敏感性低和复杂的重叠光谱，体内人类研究在技术上具有挑战性。尽管使用解耦的使用，一种众所周知的NMR方法来简化光谱，对体内研究的成功至关重 高热敏感的眼睛）和野外强度D 4T。 如我们的初步数据中所述，我们开发了一个新型的MRS脉冲序列家族，同时生成了同相和反相磁化，这导致了单个峰的总和，从而避免了对高功率解耦的需求。这是一个主要的新机会，可以显着扩大人体13c MRS脑研究的当前。这个为期两年的技术开发R21项目的目的是开发这些新的1H-13C MRS MRS方法，用于在体内测量神经元和神经胶质TCA通量以及谷氨酸/谷氨酰胺循环速率。重点是最大程度地提高灵敏度的超高场（E7 t）间接检测方法，以便在可接受的扫描时间内询问整个人脑的小组织区域（〜1 cc）。随着研究计划的成功完成，将在体外，幻象和使用大鼠动物模型中评估所得的脉冲序列，从而产生了为过渡到人类研究所需的关键初步数据。