Myelin-Specific Diffusion Tensor Imaging for Developmental Neuroimaging

描述(申请人提供)：扩散张量成像(DTI)的出现提供了一种独特的手段，通过水的扩散特性来研究人脑中白质的完整性及其对神经元功能的影响。在过去的十年里，DTI在临床诊断中的应用逐渐增加。然而，目前使用弥散张量成像对白质完整性的描述往往缺乏组织特异性。例如，最常用的定量指标之一分数各向异性(FA)可以是轴突和髓鞘中多个来源的综合结果。因此，FA的变化(以及相关的轴向和径向扩散系数)往往不能清楚地归因于特定的来源。为了实现DTI的组织特异性，并考虑到髓鞘在脑成熟和发育中的关键作用，我们建议开发一种新的获取技术，该技术可以区分脑白质微结构的变化和对髓鞘的敏感性和特异性，并计划展示其在人类翻译应用中的适用性。具体地说，我们提出了一项渐进的研究计划：1)利用稀疏矩阵中的k空间采集(KSPA)和能谱分析(KESA)开发高信噪比、空间精度和低运动敏感性的并行螺旋采集序列；2)开发磁化传递对比成像、刺激回声DTI，以灵敏地成像髓鞘微结构，并在体外验证髓鞘选择性；3)在多发性硬化症的体内验证髓鞘特异性DTI，并在儿科脑中开展初步应用，以优化全面的DTI方案，并评估其在儿童发育神经成像中潜在的巨大影响。由于这一方法除了有助于量化髓鞘的含量外，还可以帮助具体量化髓鞘的微观结构变化，因此该项目的成功完成可以对更好地了解健康大脑成熟过程中的髓鞘形成过程以及疾病和衰老过程中的脱髓鞘过程产生直接和即时的影响，从而在发育和临床神经科学中获得更广泛的应用。公共卫生相关性：最近出现的扩散张量成像(DTI)为研究人员提供了一种新的手段，通过水的扩散特性来研究白质结构。然而，由此得到的弥散各向异性图往往缺乏组织特异性，导致对脑白质变化及其对脑部疾病的影响的评估不确定。我们提出了一种新的DTI技术，除了可以区分白质内髓鞘和轴突的微结构变化外，还可以区分髓鞘和轴突的微结构变化，从而提高对它们在大脑发育成熟过程中各自作用的理解。该项目的成功完成将极大地提高目前DTI方法的组织特异性，扩大其在发育神经成像中的临床适用性。

DESCRIPTION (provided by applicant): The emergence of diffusion tensor imaging (DTI) provides a unique means via water diffusion characteristics to investigate the white matter integrity in the human brain and its impact on neuronal functions. Over the past ten years, DTI has seen gradually increased utility in its application in clinical diagnosis. However, the characterization of white matter integrity using DTI, as it stands today, often lacks tissue specificity. For example, one of the most commonly used quantitative indices, the fractional anisotropy (FA), can be the composite result of multiple sources in axons and myelin. As such, the changes in FA (as well as the related axial and radial diffusivity) often cannot be clearly attributed to a particular origin. In an effort to achieve tissue specificity for DTI, and given the crucial role of myelin in brain maturation and development, we propose to develop a new acquisition technique that can differentiate white matter microstructural changes with sensitivity and specificity to myelin, and make plans to demonstrate its applicability in translational human applications. Specifically, we propose a progressive research plan to: 1) develop a parallel spiral acquisition sequence for high SNR, spatial accuracy and low motion sensitivity using k-space acquisition in sparse matrix (kSPA) and energy spectrum analysis (KESA); 2) develop a magnetization transfer contrast prepared, stimulated-echo DTI to sensitively image myelin microstructure and validate the myelin selectivity in vitro; 3) validate the myelin-specific DTI in vivo in multiple sclerosis, and carry out initial application in pediatric brains to optimize a comprehensive DTI protocol and evaluate its potentially large impact in pediatric developmental neuroimaging. Because this methodology can help specifically quantify the microstructural changes, in addition to the content, of the myelin, a successful completion of this project can have a direct and immediate impact on better understanding the myelination process during healthy brain maturation, as well as the demyelination process in disease and during aging, thereby leading to wider applications in developmental and clinical neurosciences. PUBLIC HEALTH RELEVANCE: Recent emergence of diffusion tensor imaging (DTI) provides researchers a new means to investigate white matter structure through water diffusional characteristics. However, the resultant maps on diffusion anisotropy often lacks tissue specificity, leading to inconclusive assessment of white matter changes and their impact on brain disorders. We propose here a new DTI technique that can differentiate the microstructural, in addition to the content, changes in myelin from that in axon within the white matter, thereby improving the understanding of their respective roles in brain maturation in developmental brains. A successful completion of this project will greatly improve the tissue specificity of the current DTI methodology, broadening its clinical applicability in developmental neuroimaging.