In vivo Quantitative Magnetic Resonance Imaging of Myelin Plasticity

髓磷脂可塑性的体内定量磁共振成像

• 批准号: RGPIN-2018-05176
• 负责人: Tardif, Christine
• 金额: $ 2.11万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761362
• 关键词: vivo; Quantitative; Magnetic; Resonance; Imaging

Quantitative Magnetic Resonance Imaging of Myelin PlasticityThe brain is a highly plastic organ, it has the lifelong ability to alter its structure and function in response to experience. While the neuroscience community has long focused on neuronal and synaptic plasticity, it is now clear that myelin is also an important structural pillar of brain plasticity. Myelin is a lipid-rich sheath wrapped around axons, and is adapted to achieve and maintain the rapid conduction and synchronous timing of information in the brain. Recent studies have started to identify the mechanisms that regulate adaptive myelination. There is now a critical need for translational tools to bridge the gap between these mechanisms identified in rodent models and their impact on human behaviour. Magnetic resonance imaging (MRI) is a powerful non-invasive tool that can be used to investigate the spatio-temporal dynamics of brain microstructure in vivo. Several quantitative MRI measures have been proposed as in vivo biomarkers of myelin content, but their specificity if often questioned. The goal of this research program is to develop a translational quantitative MRI framework to study myelin plasticity in vivo in mice and humans. I have previously developed quantitative MRI acquisition and analysis techniques to map myelin content in vivo and post mortem. I have applied these techniques to study the normal variation in cortical myelin content in healthy adults, the relationship between cortical myelin maps and functional brain networks, and to improve the detection of demyelinated cortical lesions in multiple sclerosis. My group will build upon this expertise to address important limitations of current quantitative MRI techniques in order to study subtle adaptive changes in myelination due to experience. The program includes the development of novel MRI acquisition techniques, biophysical models of myelin content in the white and grey matter, and validation of the sensitivity and specificity of these MR contrasts mechanisms in mouse models of adaptive myelination.My research program will enable future research on myelin plasticity, such as the impact of age and environment on our capacity for adaptive myelination in the different areas and myelinated networks of the brain. It will facilitate knowledge translation between labs investigating myelin plasticity in mouse models and humans. Given the multi-disciplinary expertise housed at the MNI, and our collaborations with other MRI groups in Montreal and internationally, we are uniquely positioned to train the next generation of neuroimaging scientists and make significant contributions to the exciting new field of myelin plasticity via advanced imaging tools.

髓鞘可塑性的定量磁共振成像大脑是一个高度可塑性的器官，它具有终身改变其结构和功能的能力，以响应经验。虽然神经科学界长期以来一直专注于神经元和突触可塑性，但现在很清楚髓鞘也是大脑可塑性的重要结构支柱。髓鞘是包裹在轴突周围的富含脂质的鞘，并且适于实现和维持大脑中信息的快速传导和同步定时。最近的研究已经开始确定调节适应性髓鞘形成的机制。现在迫切需要翻译工具来弥合啮齿动物模型中确定的这些机制与其对人类行为的影响之间的差距。磁共振成像（MRI）是一种强有力的无创工具，可用于研究在体脑微结构的时空动力学。已经提出了几种定量MRI测量作为髓磷脂含量的体内生物标志物，但其特异性经常受到质疑。该研究计划的目标是开发一个翻译定量MRI框架，以研究小鼠和人类体内髓鞘可塑性。我以前开发了定量MRI采集和分析技术，以映射髓磷脂含量在体内和死后。我已经应用这些技术来研究正常变化的皮质髓鞘含量在健康成人，皮质髓鞘地图和功能性脑网络之间的关系，并提高多发性硬化症脱髓鞘皮质病变的检测。我的小组将在此基础上，解决目前定量MRI技术的重要局限性，以研究髓鞘形成的微妙适应性变化，由于经验。该计划包括开发新的MRI采集技术，白色和灰质中髓鞘含量的生物物理模型，以及在适应性髓鞘形成的小鼠模型中验证这些MR对比机制的灵敏度和特异性。我的研究计划将使未来的髓鞘可塑性研究成为可能，例如年龄和环境对我们在大脑不同区域和有髓鞘网络中适应性髓鞘形成能力的影响。它将促进在小鼠模型和人类中研究髓鞘可塑性的实验室之间的知识翻译。鉴于MNI的多学科专业知识，以及我们与蒙特利尔和国际上其他MRI小组的合作，我们具有独特的优势，可以培养下一代神经影像科学家，并通过先进的成像工具为令人兴奋的髓鞘可塑性新领域做出重大贡献。