Development of metabolic and molecular imaging by simultaneous PET-MRI for studying dementia and neurodegeneration.

通过同步 PET-MRI 开发代谢和分子成像，用于研究痴呆和神经退行性疾病。

• 批准号: 1953192
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1953192
• 关键词: Development; metabolic; molecular; imaging; simultaneous

Keywords: Tissue disease and degeneration, NeurodegenerationPositrom Emission Tomography, Imaging, Alzhemier's DiseaseRecent MRC investment has established a network of PET-MRI scanners targeted for neuroimaging research in dementia under the umbrella of Dementias Platform UK (DPUK). This new technology combines positron emission tomography (PET) within the same scanner as the magnetic resonance imaging (MRI) system to allow simultaneous collection of molecular imaging (PET), structural, physiological and metabolic data (MRI). These scans can provide a comprehensive, non-invasive assessment of disease processes in a single examination. However, the true capabilities of this new generation of imaging technology have not been yet determined. We have extensive experience developing and applying quantitative MRI and PET tracer studies in dementia and this project will extend our previous research to explore the capabilities of PET-MRI technology. The project will focus on developing MR spectroscopy (MRS) methods on the PET-MRI platform to allow important brain metabolites to be quantified alongside the molecular imaging measurement from PET. This work will shape the future use of both MRI and simultaneous PET-MRI in dementia research and clinical diagnosis and will be carried out in close collaboration with the scanner manufacturer.The project will be divided into 2 specific phases:1) An important target for dementia research is beta-amyloid deposition within the neurodegenerative processes. Amyloid levels can be assessed using PET imaging via appropriate radiotracers, but the need for local radiotracer production and the small nationally installed base of PET scanners will limit the use of PET as a routine diagnostic tool. Recent post-mortem studies have suggested that the glial and neuronal density changes which can be quantified by MRS measurements are sensitive to amyloid and tau respectively. As MRI is widely available, the use of MRS as a surrogate measure of amyloid could have a significant impact in dementia diagnosis. Post-mortem studies are however inherently limited to measuring pathological burden in end stage disease and so in vivo imaging research is essential to determine the relevance of post-mortem observations to living patients. Phase 1 of this project will develop proton-MRS imaging methodology (MRSI) to create spatial maps of neuronal and glial density. Amyloid PET imaging is available for dementia research in Newcastle (18F-Amyvid is regularly used). By using these new MRSI methods as part of the simultaneous PET-MRI measurements, we will determine the strength of the relationship between the PET and MRS assessment of amyloid. This work will determine the applicability of the MRSI technique as a surrogate diagnostic marker for amyloid in dementia. 2) Alzheimer's disease (AD) is characterised by regional cortical hypometabolism assessed by PET 18F-deoxyglucose (FDG) scans to measure metabolic rate of glucose consumption. One hypothesised mechanism for this hypometabolism is mitochondrial dysfunction, but this has been difficult to assess in living patients. Phosphorus MRS (31P-MRS) quantifies tissue energetics by mapping phosphocreatine and ATP levels which, when combined with appropriate modulation of regional brain activity, can indirectly assess mitochondrial activity.Phase 2 will use the specialised multi-nuclear capability of our PET-MRI scanner to develop 31P-MRS combined with FDG PET-MRI measurements to study the areas of posterior cortical hypo-metabolism seen in AD patients with a view to assessing the degree of mitochondrial dysfunction.

关键词：组织疾病和变性、神经变性正发射断层扫描、成像、阿尔茨海默病 MRC 最近的投资建立了一个 PET-MRI 扫描仪网络，在英国痴呆症平台 (DPUK) 的保护下，针对痴呆症的神经影像学研究。这项新技术将正电子发射断层扫描 (PET) 与磁共振成像 (MRI) 系统结合在同一扫描仪中，从而可以同时收集分子成像 (PET)、结构、生理和代谢数据 (MRI)。这些扫描可以在一次检查中对疾病过程进行全面、非侵入性的评估。然而，这种新一代成像技术的真正功能尚未确定。我们在开发和应用痴呆症定量 MRI 和 PET 示踪剂研究方面拥有丰富的经验，该项目将扩展我们之前的研究，探索 PET-MRI 技术的功能。该项目将重点开发 PET-MRI 平台上的磁共振波谱 (MRS) 方法，以便在 PET 分子成像测量的同时对重要的大脑代谢物进行量化。这项工作将塑造 MRI 和同步 PET-MRI 在痴呆症研究和临床诊断中的未来应用，并将与扫描仪制造商密切合作进行。该项目将分为 2 个具体阶段：1) 痴呆症研究的一个重要目标是神经退行性过程中的 β-淀粉样蛋白沉积。可以通过适当的放射性示踪剂使用 PET 成像来评估淀粉样蛋白水平，但对本地放射性示踪剂生产的需求以及全国范围内安装的 PET 扫描仪数量较少将限制 PET 作为常规诊断工具的使用。最近的尸检研究表明，可通过 MRS 测量量化的神经胶质和神经元密度变化分别对淀粉样蛋白和 tau 蛋白敏感。由于 MRI 的广泛应用，使用 MRS 作为淀粉样蛋白的替代测量可能会对痴呆症的诊断产生重大影响。然而，尸检研究本质上仅限于测量终末期疾病的病理负担，因此体内成像研究对于确定尸检观察与活体患者的相关性至关重要。该项目的第一阶段将开发质子 MRS 成像方法 (MRSI)，以创建神经元和神经胶质密度的空间图。淀粉样蛋白 PET 成像可用于纽卡斯尔的痴呆症研究（经常使用 18F-Amyvid）。通过使用这些新的 MRSI 方法作为同步 PET-MRI 测量的一部分，我们将确定 PET 和 MRS 淀粉样蛋白评估之间关系的强度。这项工作将确定 MRSI 技术作为痴呆症淀粉样蛋白替代诊断标记物的适用性。 2) 阿尔茨海默病 (AD) 的特点是局部皮质代谢减退，通过 PET 18F-脱氧葡萄糖 (FDG) 扫描来测量葡萄糖消耗的代谢率。这种代谢低下的一种假设机制是线粒体功能障碍，但这在活着的患者中很难评估。磷 MRS (31P-MRS) 通过绘制磷酸肌酸和 ATP 水平来量化组织能量，当与区域大脑活动的适当调节相结合时，可以间接评估线粒体活动。第二阶段将使用我们的 PET-MRI 扫描仪的专门多核功能来开发 31P-MRS 与 FDG PET-MRI 测量相结合，以研究后皮质区域 AD 患者代谢低下，旨在评估线粒体功能障碍的程度。