MR Microimaging of Mouse Brain Development

项目描述（申请人提供）：本课题旨在结合MRI成像的三维对准精度和连续组织切片图像的高分辨率，开发发育中的小鼠大脑三维解剖分析工具。MRI成像的特殊新功能将是扩散张量成像（DTI）的实现，这是一种新型MRI，可以基于水扩散的测量提供独特的图像对比度。由于水倾向于沿着一个体积内的定向结构扩散，DTI有效地描绘了大脑内的各种早期结构。对于尚未形成髓磷脂的未成熟大脑来说，这是一项特别重要的技术进步，因为在这些发育阶段的大脑几乎没有常规MRI检测到的内在对比。在这项建议中，我们将重点发展技术和数据库，这将是通过以下四个目标实现长期目标的重要组成部分。首先，从妊娠第11天至第19天，每隔3天至第21天，然后每周至12周龄，获得发育中的胚胎和新生儿的mri数据库。其次，通过改进的快速自旋回波技术（将采集时间减少8倍）和并行成像（将时间减少2倍）的组合，DTI可访问的超大数据集的采集速度将得到弥补。第三，从胚胎第11天到成年的所有阶段，大量连续切片和染色的小鼠大脑是可用的，切片图像将被数字捕获并根据常见的解剖标志弹性扭曲到MRI标准。从这项研究中，将识别和分配磁共振可见结构。然后，对齐的MRI和组织学图像将通过自动“播种”算法和“神经解剖学专家”的结合，通过修改我们为成年小鼠大脑开发的基于unix的3D软件，手工追踪轮廓，分割成细胞组和轴突束。最后，计算神经解剖学的工具将被开发用于可靠的定量测量标本之间的形态差异。这个项目是通过与博士合作而成为可能的。Moil (MRI), Sidman（神经解剖学）和Miller（计算神经解剖学）。

DESCRIPTION (provided by applicant): This proposal aims to develop 3D anatomical analysis tools of the developing mouse brain, combining the 3D alignment precision of MRI imaging and the higher resolution of serial histological section images. The special new features of the MRI imaging will be the implementation of diffusion tensor imaging (DTI), a new type of MRI that can provide unique image contrast based on measurement of water diffusion. Since water tends to diffuse along oriented structures within a volume, DTI serves effectively to delineate various early structures within the brain. This is a particularly important technical advance for the immature brain which has not yet formed myelin, because the brain at these stages of development has little intrinsic contrast detectable by conventional MRI. In this proposal, we will focus on development of technologies and databases that will be essential components for the long-term goal through the following four aims. First, MRI-based database of developing embryo and neonates will be acquired from days 11 to 19 of gestation, at 3-day intervals postnatally to day 21, and weekly thereafter to 12 weeks of age. Second, the slowness of acquisition of the very large datasets accessible by DTI will be offset by combination of a modified fast spin echo technique that will reduce acquisition time by a factor of 8, and parallel imaging that will reduce the time factor by 2. Third, a large series of serially-sectioned and stained mouse brains at all stages from embryonic day 11 to adulthood are available, and section images will be digitally captured and elastically warped to the MRI standards, based on common anatomical landmarks. From this study, MR-visible structures will be identified and assigned. Then the aligned MRI and histological images will be segmented into cell groups and axonal tracts by a combination of automated "seeding" algorithms and "neuroanatomical expert" hand-tracing of contours by modifications of Unix-based 3D software that we have developed for the adult mouse brain. Finally, tools for computational neuroanatomy will be developed for reliable quantitative measures of morphological differences between specimens. This project was made possible through collaboration with Drs. Moil (MRI), Sidman (neuroanatomy), and Miller (computational neuroanatomy).