Creation of an atlas to study the role of myelin in normal brain function

定量磁共振成像(MRI)比定性MRI具有更高的重复性和可解释性。这个项目的重点是一种名为髓磷脂水分成像(MWI)的定量MRI技术，该技术产生与髓鞘含量(髓鞘水分分数，MWF)相关的测量结果。 在健康的人脑中，我们对髓鞘特性的了解存在很大差距，这主要是由于缺乏灵敏、特异的活体髓鞘测量技术。更好地了解影响髓鞘含量和功能的正常变异和自然因素，将对生物学和神经科学领域具有非常重要的价值。 长期目标是在健康的人脑中创建一个涵盖广泛个体的MWF定量图谱，以研究髓鞘在正常大脑功能中的作用。 短期目标是： 1.为最先进的MRI扫描仪开发和优化MWI 我们将为目前正在安装的飞利浦3特斯拉核磁共振扫描仪实施和优化MWI序列。我们将增加回波数量，减少回波间隔，平衡自旋和梯度回波，并采用替代数据采样方案。 2.验证MWI是否为髓鞘厚度的函数 我们将比较固定组织样本的MWF测量与电子显微镜测量的髓鞘厚度以及其他定量MRI技术。我们还将比较体内MWF测量与其他先进MRI序列得出的髓鞘含量和厚度相关的参数。 3.扩展MWI以跨不同供应商的其他MRI扫描仪工作 我们将与其他网站合作，为其他主要MRI供应商开发MWI，并比较不同机器之间的测量结果。这将包括理解和描述梯度强度、射频脉冲形状和并行成像方案的影响。 4.解决创建健康的髓鞘图谱的技术考虑 来自健康参与者的数据将利用现有研究的杠杆作用，以及前瞻性收集。我们将使用商业上可用的工具和内部设计的软件相结合来解决与注册、翘曲和分割相关的问题。 5.使用髓鞘图谱描述个体间髓鞘水平的正常差异 我们将使用髓鞘图谱来确定正常人群中髓鞘含量的范围，以及与年龄、教育程度、脑结构、神经束大小和相关灰质结构大小的相关性。 拟议研究的意义 拟议的研究计划侧重于研究髓鞘在正常大脑功能中的作用。这将有助于拓宽我们对髓鞘生物学和生理学的理解。这里使用的方法还可以进一步应用于其他一系列定量成像技术和参数，提供有关中枢神经系统的其他生物学方面的信息。

Quantitative magnetic resonance imaging (MRI) is far more reproducible and interpretable than qualitative MRI. This program is focused around a quantitative MRI technique called myelin water imaging (MWI), which produces a measurement related to myelin content (myelin water fraction, MWF). There are large gaps in our knowledge of myelin characteristics in the healthy human brain, largely due to the lack of a sensitive, specific, in vivo myelin measurement technique. A better understanding of the normal variation and natural factors affecting myelin content and function would be invaluable to the fields of biology and neuroscience. The long-term objective is to create a quantitative MWF atlas in healthy human brain across a wide range of individuals to study the role of myelin in normal brain function. The short-term objectives are to: 1. Develop and optimise MWI for a state-of-the-art MRI scanner We will implement and optimise a MWI sequence for a Philips 3 Tesla MRI scanner currently under installation. We will increase the number of echoes, decrease echo spacing, balance spin and gradient echoes, and employ alternate data sampling schemes. 2. Validate MWI as a function of myelin sheath thickness We will compare MWF measurements from fixed tissue samples to electron microscopy measurements of the myelin sheath thickness as well as other quantitative MRI techniques. We will also compare in vivo MWF measurements to parameters related to myelin content and thickness derived from other advanced MRI sequences. 3. Extend MWI to work across other MRI scanners from different vendors We will collaborate with other sites to develop MWI for other major MRI vendors, and compare measurements between machines. This will include understanding and characterising the effects of gradient strengths, radio frequency pulse shapes, and parallel imaging schemes. 4. Tackle the technical considerations of creating a healthy myelin atlas Data from healthy participants will be leveraged from existing studies, as well as collected prospectively. We will address issues related to registration, warping, and segmentation using a combination of commercially available tools and in-house designed software. 5. Use the myelin atlas to characterize normal variation in myelin levels between individuals We will use the myelin atlas to determine the range of myelin content within the normal population, and dependencies on age, education, brain structure, tract size, and associated grey matter structure size. Significance of the proposed research The proposed research program is focused on studying the role of myelin in normal brain function. It will help to broaden our understanding of myelin biology and physiology. The methods employed here can be further applied to a wide range of other quantitative imaging techniques and parameters, providing information about additional biological aspects of the central nervous system.