Quadri-nuclear MRI to Study Brain Energy Metabolism

项目摘要 大脑能量代谢异常与包括阿尔茨海默氏症在内的各种病理密切相关 疾病、创伤性脑损伤、癌症和脑缺血。磁共振波谱与成像 (MRI)允许对原子核(质子1H、磷31P、钠23Na和氢2H)进行非侵入性观察 存在于许多代谢物和离子中，它们在代谢过程的不同阶段起着关键作用。到现在为止 在这一点上，技术挑战阻碍了对两个以上原子核的同时研究，这可能 隐藏代谢功能之间的因果关系和时间关系。在这个项目中，我们建议工程- 需要四核磁共振成像(4X-MRI)硬件系统、采集方法和处理流水线，以实现 在同一扫描中同时或交叉测量质子、钠、磷和氢 协议。超高fi场强磁共振成像(7T)由于其信号强度优势，是多核磁共振成像的一种天然的fit。怎么- 尽管如此，仍然需要定制硬件和获取方法来与共振的自旋进行交互 在不同频率(7特斯拉、297兆赫的1H、120兆赫的31P、79兆赫的23Na、46兆赫的2H)和 EFfi很好地适应了一系列自旋动力学。我们将实现四倍调谐射频(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。新的硬件将 与定制脉冲序列配对，这些序列利用自旋弛豫时间之间显著的fi差异来 在一次检查中实现多核收购。总而言之，本研究中开发的工具将使 动态代谢神经成像，将提供充分的fi原理证明，以支持广泛的体内 研究健康、疾病和挑战范式。该试点项目的SPECIfic目标是：(1)数据获取： 1H/31P/23Na/2H磁共振在7T(1.A)建立一个四倍调谐的32通道射频线圈。(1.b)开发可执行的fl 4X-MRI扫描方案，多核交叉扫描。(2)数据处理：定量信息建模。 从4X-MRI数据中获得信息。(2.a)从所有多核收购中优化量化fi阳离子的方法，如 以1H数据为松弛时间，23Na数据为细胞内钠浓度，代谢物浓度为 (葡萄糖、谷氨酸/谷氨酰胺、乳酸)来自标记的2H-葡萄糖摄取量、代谢物浓度(ATP、磷酸- 肌酸)从31便士开始。(2.b)模体的精确度和准确度。(3)体内应用：(3.a)评估重复性 4X-MRI在健康受试者中的重复性。(3)评价4X-fi对患者的敏感性和特异性 患有狭窄闭塞症(SOD)。我们将用4X-MRI对患有SOD的患者进行扫描，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 有兴趣在活体内测量与脑能量相关的多个参数，用于诊断或预后 疾病，但在治疗期间也是如此。

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.