The influence of myelin ultrastructure in determining magnetic resonance contrast

磁共振成像（MRI）是研究大脑和脊髓（也称为中枢神经系统（CNS））的强大技术。核磁共振成像测量的信号主要来自水——水的位置和行为提供了有关组织结构的信息。尽管MRI用于中枢神经系统成像已有30多年的历史，但对MRI信号产生的具体因素仍知之甚少。例如，在大脑发育过程中发生的MRI对比变化的原因需要更多的研究。此外，在不同的大脑和脊髓区域可以看到MRI对比的变化，但这种信号变化的来源尚不清楚。中枢神经系统组织的一个主要组成部分是髓磷脂，它在大脑和脊髓周围的结构有所不同。髓磷脂是包围神经细胞的一种绝缘鞘，它使信号快速传递，对中枢神经系统的功能至关重要。髓磷脂对MRI信号的影响尚未详细研究，但可能非常重要。髓磷脂由多层蛋白质和脂质组成。由于核磁共振扫描仪的局限性，我们无法从髓磷脂脂质和蛋白质中获得信号。然而，髓磷脂也含有约40%的水，这些水存在于脂质/蛋白质层之间。这种“髓磷脂水”可以用我们开发的一种特殊的先进MRI方法来测量，这种方法已被证明与髓磷脂脂质/蛋白质层有关。鉴于MRI的广泛应用，确定髓磷脂如何影响中枢神经系统的MRI对比是很重要的。例如，髓磷脂脂质和蛋白质含量的区域差异以及髓磷脂厚度的差异会影响MRI测量结果。我们研究的长期目标是了解组织微观结构如何影响中枢神经系统的MRI对比。在短期内，我们的研究将集中在确定髓磷脂结构如何驱动正常组织的MRI信号差异。不同年龄的健康动物的大脑和脊髓将接受标准和高级核磁共振扫描。然后用显微镜检查中枢神经系统内不同细胞的特征，并与MRI扫描结果进行比较。我们还将研究髓磷脂结构的变化如何影响我们通过MRI看到的变化。髓磷脂结构异常的大脑和脊髓将通过核磁共振和显微镜进行研究。将显微镜下看到的与核磁共振成像（MRI）相比较，将有助于我们理解与髓磷脂结构异常相关的MRI信号的变化。这项工作很重要，因为MRI是研究中枢神经系统的常用成像技术，对于理解决定对比度和导致信号变化的因素至关重要。我们将制作第一个全面的图谱，描述健康中枢神经系统组织中MRI对比与髓鞘结构之间的关系。通过评估改变的髓磷脂，我们将确定哪些MR特征可以区分结构正常和结构异常的髓磷脂。

Magnetic resonance imaging (MRI) is a powerful technique for studying the brain and spinal cord which is also called the central nervous system (CNS). The signal that MRI measures comes mainly from water - the location and behaviour of the water gives information about tissue structure. Despite the fact that MRI has been used to image the CNS for over three decades, the specific factors that contribute to the MRI signal are still poorly understood. For example, the cause of MRI contrast changes that happen during brain development needs more research. Also, variation in MRI contrast is seen in different brain and spinal cord regions, but the source of this signal variation is unknown. A major component of CNS tissue that varies structurally around the brain and spinal cord is myelin. Myelin is an insulating sheath that surrounds nerve cells - it makes signals travel quickly and is crucial to CNS function. The influence of myelin on MRI signal has not been studied in detail, but is likely very important. Myelin is made up of many layers of proteins and lipids. Because of the limitations of the MRI scanner, we cannot get signal from the myelin lipids and proteins. However, myelin also contains ~40% water which is found between the lipid/protein layers. This `myelin water' can be measured with a special advanced MRI method we have developed that has been proven to be related to the myelin lipid/protein layers. Given the widespread use of MRI, determining how myelin influences MRI contrast in the CNS is important. For example, regional variations in myelin lipid and protein content and differences in myelin thickness would influence MRI measurements. The long term goal of our research is to understand how tissue microstructure influences MRI contrast in the CNS. In the short term, our research will focus on determining how myelin structure drives MRI signal differences in normal tissue. Brains and spinal cords from healthy animals of various ages will get standard and advanced MRI scans. The characteristics of different cells inside the CNS will then be examined with a microscope and compared to the MRI scans. We also will study how changes to myelin structure impacts changes we can see with MRI. Brains and spinal cords that have structurally abnormal myelin will be studied with MRI and a microscope. Comparing what we see with the microscope to the MRI will help us understand variations of MRI signal linked to structurally abnormal myelin. This work is important because MRI is a commonly used imaging technique for studying the CNS and it is crucial to understand what determines contrast and causes signal variations. We will produce the first comprehensive atlas describing the relationship between MRI contrast and myelin structure in healthy CNS tissue. By assessing myelin that has been altered, we will identify what MR characteristics can differentiate structurally normal from structurally abnormal myelin.