CEST MRI to study BrAin MetaBolism and Function: insights from OptO fMRI and MR spectroscopy

CEST MRI 研究大脑代谢和功能：来自 OptO fMRI 和 MR 光谱的见解

• 批准号: 406818964
• 负责人: Professor Dr. Cornelius Faber
• 金额: --
• 依托单位: CEA Centre de Saclay
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406818964?language=en
• 关键词: CEST; MRI; study; BrAin; MetaBolism

Chemical exchange saturation transfer (CEST) and chemical exchange spin-lock (CESL) MRI are powerful tools for metabolic imaging. Detection of specific neurometabolites can be performed using CEST/CESL MRI with enhanced sensitivity, and temporal and spatial resolution compared to NMR Spectroscopy (MRS), by imaging the reduction in bulk water signal after application of dedicated presaturation or spin-locking modules. CEST protocols for imaging of a large number of different metabolites have been developed, and promising applications in different disciplines (e.g. oncology, musculoskeletal imaging, physiology or neuroscience) have been demonstrated. Recently, we employed CEST MRI to image glucose (glucoCEST) changes induced by sensory stimulation, and have shown that CEST functional MRI (CEST-fMRI) is a promising surrogate for detecting increased glycolytic activity during neural activation. One general limitation for CEST-fMRI is that signal changes cannot be unambiguously assigned to exclusively one metabolite. This is of particular concern for neuroimaging, since a number of transient changes in energy metabolites and neurotransmitter levels are involved.In this project, we aim to elucidate the contributions of three major neurometabolites, glucose, lactate and glutamate, to the contrast detected during functional CEST/CESL experiments, and to develop and optimize these new CEST/CESL-fMRI techniques to study the coupling between energy metabolism and neurotransmission during neural activation. Our CEST/CESL-fMRI protocols will be implemented conjointly at high magnetic field strength on two small animal scanners, in France and Germany, and used to map concentration changes of these metabolites in the rat brain. To verify the specificity of CEST/CESL-fMRI and to separate the contributions of individual metabolites, localized 1H and indirect 1H-{13C} MRS techniques will be employed by the French partners. To further assess cell type-specific contributions to the CEST/CESL signal, optogenetic methods will be used simultaneously with MRI by the German partners. Viral transduction will be used to express both opsins and fluorescence reporter proteins for calcium, lactate, or glutamate in defined cell types (neurons, astrocytes). Cell type-specific read out of fluorescence signal upon sensory or cell type-specific (optogenetic) stimulation will enable us to identify individual contributions to the observed functional CEST/CESL signal.The outcome of this work will consist in robust and validated acquisition protocols with a strong potential for use in other organs. Application in humans may be facilitated by the upcoming high magnetic field clinical systems. At a more fundamental level, the use of CEST/CESL-fMRI methods could help exploring the metabolic coupling within the glial-neuronal-vascular functional unit during specifically designed activation paradigms in normal and pathological conditions, or following pharmacological challenges.

化学交换饱和转移（CEST）和化学交换自旋锁（CESL）MRI是代谢成像的有力工具。通过对应用专用预饱和或自旋锁定模块后大量水信号的减少进行成像，可以使用CEST/CESL MRI进行特定神经代谢物的检测，与核磁共振光谱学（MRS）相比，具有更高的灵敏度以及时间和空间分辨率。已经开发了用于大量不同代谢物成像的CEST协议，并且已经证明了在不同学科（例如肿瘤学、肌肉骨骼成像、生理学或神经科学）中的有前景的应用。最近，我们采用CEST MRI图像葡萄糖（glucoCEST）的变化引起的感觉刺激，并已表明，CEST功能性MRI（CEST-fMRI）是一个很有前途的替代检测增加糖酵解活动在神经激活。CEST-fMRI的一个普遍局限性是信号变化不能明确地分配给一种代谢物。这是神经影像学特别关注的问题，因为能量代谢物和神经递质水平的许多瞬态变化都涉及其中。在这个项目中，我们的目标是阐明三种主要的神经代谢物，葡萄糖，乳酸盐和谷氨酸盐，在功能性CEST/CESL实验中检测到的对比度的贡献，发展和优化CEST/CESL-fMRI新技术，研究神经激活过程中能量代谢与神经传递的耦合。我们的CEST/CESL-fMRI协议将在法国和德国的两个小动物扫描仪上在高磁场强度下联合实施，并用于绘制大鼠大脑中这些代谢物的浓度变化。为了验证CEST/CESL-fMRI的特异性并分离单个代谢物的贡献，法国合作伙伴将采用局部1H和间接1H-{13 C} MRS技术。为了进一步评估细胞类型特异性对CEST/CESL信号的贡献，德国合作伙伴将同时使用光遗传学方法和MRI。病毒转导将用于在限定的细胞类型（神经元、星形胶质细胞）中表达视蛋白和钙、乳酸盐或谷氨酸盐的荧光报告蛋白。在感觉或细胞类型特异性（光遗传学）刺激下的荧光信号的细胞类型特异性读出将使我们能够识别对所观察到的功能CEST/CESL信号的个体贡献。这项工作的结果将包括在其他器官中使用的强大潜力的稳健和验证的采集协议。即将到来的高磁场临床系统可能会促进人类的应用。在更基础的水平上，使用CEST/CESL-fMRI方法可以帮助探索在正常和病理条件下，或以下药理学挑战的特定设计的激活范例期间，神经胶质-神经元-血管功能单元内的代谢偶联。