Quadri-nuclear MRI to Study Brain Energy Metabolism

四核 MRI 研究脑能量代谢

• 批准号: 9893661
• 负责人: Ryan Brown
• 金额: $ 21.19万
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893661
• 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; 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; outcome forecast; 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.

项目摘要 脑能量代谢异常与包括阿尔茨海默氏症在内的多种病理密切相关 疾病，脑损伤，癌症和缺血。磁共振光谱（MRS）和成像 （MRI）允许对核观察（质子1H，磷31p，23na和2H氘） 存在于许多代谢物和离子中，它们在此代谢过程的各个阶段中扮演关键角色。为此 重点，技术挑战阻止了两个以上的核会轻松研究，这可以 隐藏代谢功能之间的因果关系和临时关系。在这个项目中，我们建议 NEER A QUADRI核MRI（4X-MRI）硬件系统，采集方法和处理管道以启用 在同一扫描中，质子，钠，磷和氘同时或交织的测量值 协议。鉴于其信号强度优势，超高领域MRI（7 t）是多核MRI的自然拟合。如何- 曾经，自定义硬件和采集方法仍然需要与引起共鸣的旋转互动 在不同的频率下（在7 Tesla，297 MHz为1H，为31p的120 MHz，为79 MHz，为23na，46 MHz为2H）和 有效地适应一系列自旋动力学。我们将实施四弦射频（RF） 线圈和硬件平台，激发和检测1H，31p，23na和2h的信号。新硬件将 与自定义的脉冲序列配对，这些脉冲序列利用自旋松弛时间之间的显着差异到 在一次检查中启用多核采集。本研究中开发的工具将启用 动态代谢神经影像学，将提供足够的原则证明，以支持各种体内 健康，疾病和挑战范式研究。该试点项目的特定目的是：（1）数据获取： 1H/31p/23na/2h MRI在7 T.（1.A）建造一个四弦调节的32通道RF线圈。 （1.b）发展一个灵活 4X-MRI协议，带有交织的多核采集。 （2）数据处理：对定量信息进行建模 从4x-MRI数据中进行介绍。 （2.a）以优化所有来自所有多核采集的量化方法， 作为1H数据的放松时间，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，裂缝），该标记为2H-葡萄糖摄取，代谢物浓度（ATP，磷酸 - 磷酸 - 肌酸）从31p开始。 （2.b）幻象的精度和准确性。 （3）在体内应用：（3.a）评估可重复性 健康受试者4倍-MRI的可重复性。 （3.b）评估患者的敏感性和4倍MRI的特定城市 患有steno colly疾病（SOD）。我们将扫描患有4倍MRI的SOD患者以测量大脑的差异 缺血性组织和正常组织之间的代谢。这个新的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有关的多个参数，以诊断或预后 疾病，也可以在治疗期间。