Proton Magnetic Resonance of Biological Systems

核磁共振是研究生物系统的一种行之有效的技术，它对结构和动力学都有很高的敏感性。由于生命过程发生在溶液中，这些体系中水的质子核磁共振应该包含重要信息。事实上，医学磁共振成像(MRI)依赖于不同类型的正常组织之间以及正常组织和病理组织之间来自组织水的信号的差异所提供的精致对比。然而，我们对这种精致的磁共振对比的根本起源的理解仍处于原始阶段。*目前我们的研究集中在人类的大脑和脊柱组织以及人体组织的动物模型上。我们的研究计划有三个主要主题：1)探索导致磁共振(MR)信号(或MRI对比)性质的基本机制。2)开发和优化磁共振技术，利用基本机制创建独特的对比；3)应用这些磁共振技术，更好地了解正常和异常的人体组织结构和功能。在过去的20年里，我们的研究小组一直致力于通过磁共振无创测量髓鞘含量。我们率先在体内测量髓鞘水分数(髓磷脂水信号的派生)，这有望提供一种准确的体内髓鞘磁共振测量。髓鞘在大脑中隔离神经元，使神经信号传导速度加快两个数量级，当髓鞘受损时，就会出现临床缺陷。髓磷脂在大脑的工作方式中扮演着重要的角色，因此，许多研究都致力于寻找在人体内对髓鞘进行成像的技术。*NSERC发现拨款研究计划的目标：(*1)通过表征髓鞘水成像的基本机制，更好地了解髓鞘水成像，特别是磁化交换的作用。(*2)探索已被提出用于测量体内髓鞘的其他磁共振技术背后的机制-mcDESPOT和非均一MT。(*3)通过缩短扫描时间和增加信噪比来进一步优化髓鞘水成像技术*4)进一步了解髓鞘在正常大脑和脊柱功能中的作用。*研究将在两个地点进行：UBC物理，在那里我们将使用核磁共振波谱仪研究体外牛(COW)脑和模拟大脑的样本；以及UBC放射学，我们将在那里研究正常的人类大脑和脊柱。*这项研究将改进用于测量大脑和脊椎髓鞘形成的MRI技术。准确测量髓鞘的能力将使评估旨在保护大脑免受脱髓鞘或诱导异常大脑重新髓鞘形成的药物的有效性。它还将有助于确定髓鞘形成在正常大脑和许多神经疾病中的作用，例如多发性硬化症。**

Nuclear magnetic resonance (NMR), with its combined sensitivity to both structure and dynamics, is a well-proven technique for the study of biological systems. Since life processes occur in solution, the proton NMR of water in these systems should contain important information. Indeed, medical magnetic resonance imaging (MRI) relies on the exquisite contrast provided by differences in signal from tissue water between different types of normal tissue and between normal and pathological tissue. However, our understanding of the fundamental origins of this exquisite MR contrast is still at a primitive stage.***At present our research is focused on brain and spine tissue in humans and animal models of human tissue. Our research program has three main themes: 1) exploring the fundamental mechanisms responsible for the nature of the magnetic resonance (MR) signal (or MRI contrast). 2) developing and optimising MR techniques which exploit the fundamental mechanisms to create unique contrasts and 3) application of these MR techniques to better understand normal and abnormal human tissue structure and function. ***For the past two decades, our research group has worked on the measurement of myelin content non invasively by MRI. We pioneered the in vivo measurement of the myelin water fraction (the faction of signal from myelin water) which promises to provide an accurate in vivo MR measure of myelin. Myelin, which insulates neurons in brain, accelerates nerve signal conduction rates by two orders of magnitude and when myelin is damaged there are clinical deficits. Myelin plays a large role in how the brain works, consequently, much research has been dedicated to finding techniques for imaging myelin in humans in vivo.****OBJECTIVES of this NSERC Discovery Grant Research Program: ***1) To better understand myelin water imaging by characterising the fundamental mechanisms, particular the role of magnetization exchange. ***2) To explore the mechanisms behind other magnetic resonance techniques which have been proposed to measure myelin in vivo - mcDESPOT and inhomogeneous MT. ***3) To further optimise the myelin water imaging technique by reducing scan time and increasing signal to noise***4) To further understand the role of myelination in normal brain and spine function ***The research will be carried out in two locations: UBC Physics where we shall use a NMR spectrometer to study ex vivo bovine (cow) brain and samples which model brain; and UBC Radiology where we shall study normal human brain and spine. ***This research will result in improvements to MRI techniques for measuring brain and spine myelination. The ability to measure myelin accurately will enable assessment of the efficacy of drugs designed to protect the brain from demyelination or to induce remyelination in abnormal brain. It will also aid in characterizing the role of myelination in normal brain and many neurological diseases, for example, multiple sclerosis. **