Myelin-Specific Diffusion Tensor Imaging for Developmental Neuroimaging

描述（由申请人提供）：扩散张量成像（DTI）的出现提供了一种独特的手段，通过水扩散特性来研究人脑白质完整性及其对神经元功能的影响。近十年来，DTI在临床诊断中的应用逐渐增加。然而，目前使用DTI对白质完整性的表征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），可以是轴突和髓磷脂多个来源的复合结果。因此，FA的变化（以及相关的轴向和径向扩散系数）通常不能明确归因于特定的起源。为了实现DTI的组织特异性，并考虑到髓磷脂在脑成熟和发育中的关键作用，我们建议开发一种新的采集技术，可以区分白质微结构变化，对髓磷脂具有敏感性和特异性，并计划证明其在转化人类应用中的适用性。具体而言，我们提出了一个渐进的研究计划：1)利用稀疏矩阵（kSPA）和能谱分析（KESA）中的k空间采集开发一个高信噪比、空间精度和低运动灵敏度的平行螺旋采集序列；2)制备磁化转移造影剂，刺激回波DTI对髓磷脂微观结构进行敏感成像，并在体外验证髓磷脂的选择性；3)在多发性硬化症患者体内验证髓磷脂特异性DTI，并在儿童大脑中进行初步应用，以优化综合DTI方案，并评估其在儿童发育神经影像学中的潜在巨大影响。由于这种方法可以帮助具体量化髓磷脂的微观结构变化，除了髓磷脂的含量，这个项目的成功完成可以对更好地理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，从而导致在发育和临床神经科学中更广泛的应用。与公共卫生相关：最近出现的弥散张量成像（DTI）为研究人员提供了一种通过水扩散特征研究白质结构的新手段。然而，所得到的扩散各向异性图往往缺乏组织特异性，导致白质变化及其对脑部疾病影响的评估不确定。在此，我们提出了一种新的DTI技术，可以区分髓鞘和轴突在白质内的微观结构变化以及含量变化，从而提高对它们在发育性大脑成熟中各自作用的理解。该项目的成功完成将大大提高当前DTI方法的组织特异性，扩大其在发育神经影像学中的临床适用性。

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.