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多种病理学密切相关 疾病、创伤性脑损伤、癌症和局部缺血。磁共振波谱（MRS）和成像 (MRI)允许对原子核（质子1H、磷31 P、钠23 Na和氘2 H）进行非侵入性观察 存在于许多代谢物和离子中，在代谢过程的各个阶段发挥关键作用。这么做的 技术挑战阻止了同时研究两个以上的原子核， 隐藏了代谢功能之间的因果关系和时间关系。在这个项目中，我们建议工程师- 需要一种四核MRI（4X-MRI）硬件系统、采集方法和处理流水线， 质子、钠、磷和氘在同一扫描中同时或交错测量 议定书鉴于其信号强度优势，超高场MRI（7 T）是多核MRI的天然选择。怎么- 尽管如此，仍然需要定制的硬件和采集方法来与共振的自旋相互作用 在不同的频率下（7特斯拉，297 MHz（1 H），120 MHz（31 P），79 MHz（23 Na），46 MHz（2 H））， 有效地适应一系列的自旋动力学。我们将实施四调谐射频（RF） 线圈和硬件平台，以激发和检测来自1H、31 P、23 Na和2 H的信号。新硬件将 与定制脉冲序列配对，利用自旋弛豫时间之间的显著差异， 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，以支持广泛的体内 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/31 P/23 Na/2 H MRI。(1.a)做一个四重调谐的32通道射频线圈。(1.b)开发一个灵活的 采用交错多核采集的4X-MRI方案。(2)数据处理：定量信息建模 从4X-MRI数据。(2.a)为了优化所有多核收购的量化方法， 作为来自1H数据的弛豫时间、来自23 Na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）从标记的2 H-葡萄糖摄取，代谢物浓度（ATP，磷酸- 肌酸（31 P）。(2.b)体模中的精密度和准确度。(3)体内应用：（3.a）评估重复性 和4X-MRI在健康受试者中的再现性。(3.b)评估4X-MRI在患者中的灵敏度和特异性 狭窄闭塞性疾病（SOD）。我们将用4X-MRI扫描SOD患者，以测量大脑中的差异 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 感兴趣的是测量与体内脑能量相关的多个参数，用于诊断或预后， 疾病，但也在治疗过程中。

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.