MR Microimaging of Mouse Brain Development

描述(申请人提供)：这项建议旨在开发发育中的小鼠脑的3D解剖分析工具，结合MRI成像的3D对准精度和连续组织切片图像的更高分辨率。磁共振成像的新特点将是实现扩散张量成像(DTI)，这是一种新型的磁共振成像，可以在测量水扩散的基础上提供独特的图像对比度。由于水倾向于在一个体积内沿定向结构扩散，DTI有效地描绘了大脑内的各种早期结构。对于尚未形成髓鞘的未成熟大脑来说，这是一项特别重要的技术进步，因为处于这些发育阶段的大脑几乎没有传统MRI可以检测到的内在对比度。在这项提案中，我们将通过以下四个目标重点开发技术和数据库，这些技术和数据库将是实现长期目标的重要组成部分。首先，基于MRI的发育胚胎和新生儿数据库将在怀孕11至19天，出生后每隔3天至第21天，此后每周至12周获得。其次，DTI可以访问的超大数据集的采集速度很慢，这将被改进的快速自旋回波技术和并行成像技术相结合来抵消，快速自旋回波技术将使采集时间减少8倍，并行成像将使时间因素减少2。第三，可以获得从胚胎第11天到成年所有阶段的大量连续切片和染色的小鼠大脑，切片图像将被数字捕获并根据常见的解剖地标进行弹性扭曲，以符合MRI标准。从这项研究中，将识别和分配MR可见结构。然后，对齐的MRI和组织学图像将被分割成细胞组和轴突束，这将通过自动的“种子”算法和“神经解剖专家”手动跟踪轮廓的组合，通过修改我们为成年小鼠大脑开发的基于Unix的3D软件来实现。最后，将开发用于计算神经解剖学的工具，以可靠地定量测量标本之间的形态差异。这个项目是通过与莫尔博士(核磁共振)、西德曼博士(神经解剖学)和米勒博士(计算神经解剖学)合作完成的。

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).