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央的各种病理过程 神经系统处于神经发育的不同阶段。一项技术的可用性能够满足非 对中枢神经系统髓鞘进行侵入性可视化和量化将大大丰富临床和基础知识 神经科学研究。一种新出现的定量磁共振成像方法可以快速而可靠地进行活体成像 基于大分子质子测量物理原理的脑和脊髓髓鞘形成 分数(MPF)。Mpf是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 由于髓鞘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人们的广泛关注 在外观正常的白质和灰质中，MPF与组织学确定的强相关性 髓鞘含量。然而，由于缺乏方法，强积金的广泛应用受到了限制 从而能够快速可靠地在活体内测量该参数。一种新开发的快速MPF映射方法 方法引入了一种测量强积金的基本新方法，在以下方面取得了重大改进 时间效率高，大大简化了图像采集和处理。在其当前状态下，快速MPF映射 以可靠、定量和简单的方式充分满足神经科学研究界尚未满足的需求 神经组织中髓鞘含量的成像生物标志物。拟议的R24资源的最终目标 是使最广泛使用的人类和动物MRI的用户可以轻松地访问MPF地图 基于标准制造商软件的设备，用于广泛的神经科学研究 项目，并启用临床翻译。为实现这些目标，将实现以下具体目标 已完成：(1)标准化最广泛使用的人类和动物MRI平台的快速MPF映射 基于由制造的人体1.5T和3T磁共振系统的一套即用协议 飞利浦、西门子和通用电气制造的7T、9.4T、11.7T、14T和16.4T磁共振系统 布鲁克和瓦里安/安捷伦使用后处理算法纠正潜在的平台依赖 MPF地图中的偏差；(2)允许基于标准的MPF地图技术的广泛分发 将包括MPF映射协议的电子版、独立重建的用户包 软件、协议执行和图像处理的标准操作程序、质量保证 和培训材料；以及(3)在17个或更多国家和地区部署快速MPF映射技术 广泛应用于临床和临床前神经科学研究的国际网站。该项目 活动将在四年内进行，涉及强积金的全面计量评估 人类和动物的测绘技术，并将由代表高级官员的指导委员会指导 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.