In vivo Quantitative Magnetic Resonance Imaging of Myelin Plasticity

髓鞘再生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，以回应经验。虽然神经科学界长期以来一直关注神经元和突触的可塑性，但现在很明显，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，适用于实现和维持大脑中信息的快速传导和同步计时。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它们对人类行为的影响之间的差距。磁共振成像(MRI)是一种强大的非侵入性工具，可以用来研究活体大脑微结构的时空动力学。一些定量的MRI方法被认为是髓鞘含量的体内生物标记物，但其特异性经常受到质疑。这项研究计划的目标是开发一种翻译定量磁共振框架，以研究在小鼠和人类体内的髓鞘可塑性。我之前已经开发了定量MRI采集和分析技术，以绘制体内和死后的髓鞘含量图。我应用这些技术来研究健康成年人皮质髓鞘含量的正常变化，皮质髓鞘地图与功能脑网络之间的关系，并改进多发性硬化症脱髓鞘皮质病变的检测。我的团队将以这一专业知识为基础，解决当前定量MRI技术的重要局限性，以便研究由于经验而导致的髓鞘形成的微妙适应性变化。该计划包括开发新的MRI采集技术，白质和灰质中髓鞘含量的生物物理模型，以及在小鼠适应性髓鞘形成模型中验证这些MR对比机制的敏感性和特异性。我的研究计划将使未来能够对髓鞘可塑性进行研究，例如年龄和环境对大脑不同区域和有髓网络中的适应髓鞘形成能力的影响。它将促进研究小鼠模型髓鞘可塑性的实验室和人类之间的知识转换。鉴于MNI拥有的多学科专业知识，以及我们与蒙特利尔和国际上其他核磁共振小组的合作，我们处于独特的地位，可以培训下一代神经成像科学家，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。

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.