Quantitative myelin mapping in vivo for clinical and pre-clinical MRI

髓鞘损伤和异常髓鞘形成经常伴随中枢神经系统的各种病理过程。 神经系统发育的不同阶段。一种技术的可用性，能够使非- 侵入性地可视化和定量CNS中髓鞘将大大丰富临床和基础 神经科学研究。一种新出现的定量MRI方法能够快速和稳健地在体内映射， 基于大分子质子测量的物理原理的脑和脊髓髓鞘形成 分数（MPF）。MPF是一种描述所涉及的大分子质子数量的生物物理参数 在生物系统中与自由水质子进行磁化交换。在过去十年，强积金计划 由于其对脱髓鞘的高度敏感性，作为髓鞘的定量生物标志物引起了显著的关注 在正常的白色和灰质中，MPF和组织学测定的MPF之间存在强相关性， 髓鞘含量然而，由于缺乏方法，MPF的广泛应用受到限制 从而允许该参数的快速和可靠的体内测量。最近开发的快速MPF映射 方法介绍了一种主要的新方法MPF测量，实现了关键的改进， 时间效率，并大大简化了图像采集和处理。在当前状态下，快速MPF映射 完全解决了神经科学研究社区在可靠，定量和简单的 神经组织中髓鞘含量的成像生物标志物。建议的R24资源的最终目标 是使MPF标测更容易为最广泛使用的人类和动物MRI的用户所用 基于标准制造商软件的设备，在广泛的神经科学研究中使用它 项目，并使临床翻译。为实现这些目标，将实现以下具体目标： 完成：（1）标准化最广泛使用的人类和动物MRI平台的快速MPF标测 基于一套人体全身1.5T和3 T MRI系统的即用型方案， Philips、Siemens和General Electric以及生产的动物7 T、9.4T、11.7T、14 T和16.4T MRI系统 由Bruker和Varian/Agilent开发，采用后处理算法校正潜在的平台依赖性 MPF映射中的偏差;（2）使MPF映射技术能够基于标准广泛分布 用户包，将包括MPF标测方案的电子版本，独立重建 软件、方案执行和图像处理的标准操作规程、质量保证 幻影，和培训材料;和（3）部署快速MPF映射技术在17个或更多的国家， 国际网站将应用于广泛的临床和临床前神经科学研究。项目 活动将在四年内进行，涉及对强积金的全面评估， 人类和动物的绘图技术，并将由指导委员会代表高级 来自华盛顿大学和合作机构的调查人员。

Myelin damage and abnormal myelination frequently accompany various pathological processes in the central nervous system at different stages of neurodevelopment. The availability of a technology capable to non- invasively visualize and quantify myelin in CNS would substantially enrich both clinical and fundamental neuroscience research. A newly emerged quantitative MRI method enables fast and robust in vivo mapping of the brain and spinal cord myelination based on the physical principle of measuring macromolecular proton fraction (MPF). MPF is a biophysical parameter that describes the amount of macromolecular protons involved into magnetization exchange with free water protons in biological systems. During past decade, MPF has attracted remarkable attention as a quantitative biomarker of myelin due to its high sensitivity to demyelination in normal-appearing white and gray matter and strong correlations between MPF and histologically determined myelin content. However, widespread applications of MPF have been limited due to the absence of methods allowing fast and reliable in vivo measurements of this parameter. A recently developed fast MPF mapping method has introduced a principally new approach for MPF measurements, achieved critical improvement in time efficiency, and greatly simplified image acquisition and processing. In its current state, fast MPF mapping fully addresses the unmet need of the neuroscience research community in a reliable, quantitative, and simple imaging biomarker of the myelin content in neural tissues. The ultimate goals of the proposed R24 resource are to make MPF mapping easily accessible to the users of most widely available human and animal MRI equipment based on standard manufacturers' software, employ it in a wide range of neuroscience research projects, and enable clinical translation. To achieve these goals, the following specific aims will be accomplished: (1) standardize fast MPF mapping for most widely used human and animal MRI platforms based on a set of ready-for-use protocols for human whole-body 1.5T and 3T MRI systems manufactured by Philips, Siemens, and General Electric and animal 7T, 9.4T, 11.7T, 14T, and 16.4T MRI systems manufactured by Bruker and Varian/Agilent with a post-processing algorithm for correction of potential platform-dependent biases in MPF maps; (2) enable widespread distribution of the MPF mapping technology based on a standard user package that will include electronic versions of MPF mapping protocols, standalone reconstruction software, standard operating procedures for protocol execution and image processing, quality assurance phantom, and training materials; and (3) deploy the fast MPF mapping technology at 17 or more national and international sites to be applied in a broad range of clinical and preclinical neuroscience research. The project activities will be carried out during four years, involve comprehensive metrological assessment of the MPF mapping technology in humans and animals, and will be guided by the Steering Committee representing senior investigators from the University of Washington and collaborating institutions.