Quadri-nuclear MRI to Study Brain Energy Metabolism

四核 MRI 研究脑能量代谢

• 批准号: 10152654
• 负责人: Ryan Brown
• 金额: $ 25.43万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152654
• 关键词: Adenosine Triphosphate; Aerobic; Alzheimer' s Disease; Astrocytes; Brain; Brain Diseases; Cell Death; Cell Nucleus; Cell Survival; Cells; Cerebral Ischemia; Computer software; Consumption; Custom; Data; Deuterium; Diagnosis; Diffusion; Disease; Energy Metabolism; Etiology; Fingerprint; Frequencies; Functional Magnetic Resonance Imaging; Generations; Glucose; Glutamates; Glutamine; Glycolysis; Goals; Health; Homeostasis; Human; Image; Imaging Device; Ions; Ischemia; Label; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Minor; Mitochondria; Modeling; Monitor; Na(+)-K(+)-Exchanging ATPase; Noise; Normal tissue morphology; Nuclear; Organ; Oxidative Phosphorylation; Oxygen; Pathology; Patients; Perfusion; Phosphocreatine; Phosphorus; Physiologic pulse; Pilot Projects; Play; Problem Solving; Process; Production; Prognosis; Protocols documentation; Protons; Recurrence; Relaxation; Reproducibility; Research Personnel; Resolution; Running; Scanning; Scheme; Scientist; Sensitivity and Specificity; Signal Transduction; Sodium; Sodium Phosphorus; Stimulus; Structure; System; Therapeutic Intervention; Time; Tissues; Transient Ischemic Attack; Traumatic Brain Injury; Variant; Water; brain metabolism; cerebral atrophy; computerized data processing; data acquisition; density; extracellular; flexibility; glucose uptake; imaging modality; imaging system; in vivo; inorganic phosphate; insight; interest; neuroimaging; neuronal metabolism; novel; prevent; radio frequency; spectroscopic imaging; tool; tumor

Project Summary Abnormalities in brain energy metabolism are strongly linked to a variety of pathologies including Alzheimer's disease, traumatic brain injury, cancer, and ischemia. Magnetic resonance spectroscopy (MRS) and imaging (MRI) allow non-invasive observation of nuclei (proton 1H, phosphorus 31P, sodium 23Na, and deuterium 2H) present in many metabolites and ions that play key roles in various stages of this metabolic process. Up to this point, technical challenges have prevented more than two nuclei from being studied simultaneously, which can conceal causality and temporal relationships between metabolic functions. In this project, we propose to engi- neer a quadri-nuclear MRI (4X-MRI) hardware system, acquisition method, and processing pipeline to enable proton, sodium, phosphorus, and deuterium simultaneous or interleaved measurements within the same scan protocol. Given its signal strength advantage, ultra-high-field MRI (7 T) is a natural fit for multinuclear MRI. How- ever, custom hardware and acquisition methods are nonetheless required to interact with spins that resonate at different frequencies (at 7 Tesla, 297 MHz for 1H, 120 MHz for 31P, 79 MHz for 23Na, 46 MHz for 2H) and efficiently accommodate a range of spin dynamics. We will implement a quadruple-tuned radiofrequency (RF) coil and hardware platform to excite and detect signals from 1H, 31P, 23Na, and 2H. The new hardware will be paired with custom pulse sequences that exploit the significant differences between spin relaxation times to enable multinuclear acquisitions in a single examination. Together, the tools developed in this study will enable dynamic metabolic neuroimaging and will provide sufficient proof-of-principle to support a wide range of in vivo studies in health, disease, and challenge paradigms. Specific aims of this pilot project are: (1) Data acquisition: 1H/31P/23Na/2H MRI at 7 T. (1.a) To build a quadruple-tuned 32-channel RF coil. (1.b) To develop a flexible 4X-MRI protocol with interleaved multinuclear acquisitions. (2) Data processing: Modeling the quantitative infor- mation from the 4X-MRI data. (2.a) To optimize methods of quantification from all multinuclear acquisitions, such as relaxation times from 1H data, intracellular sodium concentration from 23Na data, metabolite concentration (glucose, glutamate/glutamine, lactate) from labeled 2H-glucose uptake, metabolite concentration (ATP, phospho- creatine) from 31P. (2.b) Precision and accuracy in phantoms. (3) Application in vivo: (3.a) To assess repeatability and reproducibility of 4X-MRI in healthy subjects. (3.b) To assess sensitivity and specificity of 4X-MRI in patients with steno-occlusive disease (SOD). We will scan patients with SOD with 4X-MRI to measure differences in brain metabolism between ischemic and normal tissues. This new 4X-MRI tool could help researchers and clinicians interested in measuring multiple parameters related to brain energy in vivo, for both diagnosis or prognosis of diseases, but also during therapy.

项目概要 大脑能量代谢异常与包括阿尔茨海默病在内的多种病理学密切相关 疾病、创伤性脑损伤、癌症和缺血。磁共振波谱 (MRS) 和成像 (MRI) 允许非侵入性观察原子核（质子 1H、磷 31P、钠 23Na 和氘 2H） 存在于许多代谢物和离子中，在该代谢过程的各个阶段发挥关键作用。至此 一点，技术挑战阻止了同时研究两个以上的原子核，这可以 隐藏代谢功能之间的因果关系和时间关系。在这个项目中，我们建议设计 无需四核 MRI (4X-MRI) 硬件系统、采集方法和处理流程即可实现 在同一扫描中同时或交错测量质子、钠、磷和氘 协议。鉴于其信号强度优势，超高场 MRI (7 T) 非常适合多核 MRI。如何- 然而，仍然需要定制硬件和采集方法来与共振的自旋进行交互 在不同频率下（7 Tesla、1H 为 297 MHz、31P 为 120 MHz、23Na 为 79 MHz、2H 为 46 MHz） 有效地适应一系列自旋动力学。我们将实施四重调谐射频 (RF) 线圈和硬件平台，用于激励和检测来自 1H、31P、23Na 和 2H 的信号。新硬件将 与利用自旋弛豫时间之间的显着差异的定制脉冲序列配对 在一次检查中实现多核采集。总之，本研究中开发的工具将使 动态代谢神经成像，并将提供足够的原理证明来支持广泛的体内 健康、疾病和挑战范式的研究。该试点项目的具体目标是： (1) 数据采集： 7 T 下的 1H/31P/23Na/2H MRI。(1.a) 构建四调谐 32 通道射频线圈。 (1.b) 制定灵活的 具有交错多核采集的 4X-MRI 协议。 (2) 数据处理：对定量信息进行建模 4X-MRI 数据的信息。 (2.a) 优化所有多核采集的量化方法，例如 作为来自 1H 数据的弛豫时间、来自 23Na 数据的细胞内钠浓度、代谢物浓度 （葡萄糖、谷氨酸/谷氨酰胺、乳酸）来自标记的 2H-葡萄糖摄取、代谢物浓度（ATP、磷酸化） 肌酸）来自 31P。 (2.b) 体模的精度和准确度。 (3) 体内应用： (3.a) 评估重复性 以及 4X-MRI 在健康受试者中的可重复性。 (3.b) 评估 4X-MRI 对患者的敏感性和特异性 患有狭窄闭塞性疾病（SOD）。我们将使用 4X-MRI 扫描患有 SOD 的患者，以测量大脑的差异 缺血组织和正常组织之间的代谢。这种新的 4X-MRI 工具可以帮助研究人员和临床医生 有兴趣测量与体内脑能量相关的多个参数，用于诊断或预后 疾病，而且在治疗期间。