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。MRI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已被用于CNS成像超过三十年，但对MRI信号的具体因素仍然知之甚少。例如，大脑发育过程中MRI对比度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中可以看到MRI对比度的变化，但这种信号变化的来源是未知的。在脑和脊髓周围结构上不同的CNS组织的主要成分是髓磷脂。髓磷脂是一种包围神经细胞的绝缘鞘-它使信号迅速传播，对中枢神经系统功能至关重要。髓磷脂对MRI信号的影响尚未详细研究，但可能非常重要。髓鞘是由许多层的蛋白质和脂质。由于MRI扫描仪的局限性，我们无法从髓鞘脂质和蛋白质中获得信号。然而，髓磷脂还含有约40%的水，其存在于脂质/蛋白质层之间。这种“髓鞘水”可以用我们开发的一种特殊的先进MRI方法来测量，该方法已被证明与髓鞘脂质/蛋白质层有关。鉴于MRI的广泛使用，确定髓鞘如何影响CNS中的MRI对比度是重要的。例如，髓鞘脂质和蛋白质含量的区域变化以及髓鞘厚度的差异会影响MRI测量。我们研究的长期目标是了解组织微结构如何影响CNS的MRI对比度。在短期内，我们的研究将集中在确定髓鞘结构如何驱动正常组织中的MRI信号差异。来自不同年龄健康动物的大脑和脊髓将得到标准和先进的MRI扫描。然后将用显微镜检查CNS内不同细胞的特征，并与MRI扫描进行比较。我们还将研究髓鞘结构的变化如何影响我们可以通过MRI看到的变化。具有结构异常髓鞘的大脑和脊髓将用MRI和显微镜进行研究。将我们在显微镜下看到的与MRI进行比较，将有助于我们了解与结构异常髓鞘相关的MRI信号变化。这项工作很重要，因为MRI是研究CNS的常用成像技术，了解什么决定对比度并导致信号变化至关重要。我们将制作第一个描述健康CNS组织中MRI对比度和髓鞘结构之间关系的综合图谱。通过评估已经改变的髓鞘，我们将确定哪些MR特征可以区分结构正常的髓鞘和结构异常的髓鞘。

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.