MR Microimaging of Mouse Brain Development

描述（由申请人提供）：该提案旨在开发发育中小鼠大脑的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。MRI成像的特殊新功能将是扩散张量成像（DTI）的实现，这是一种新型的MRI，可以根据水扩散的测量提供独特的图像对比度。由于水倾向于在体积内沿沿着定向结构扩散，因此DTI有效地用于描绘脑内的各种早期结构。这对于尚未形成髓鞘的未成熟大脑来说是一个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通过常规MRI检测到的内在对比度。在本提案中，我们将重点开发技术和数据库，这些技术和数据库将通过以下四个目标成为长期目标的重要组成部分。首先，将从妊娠第11 - 19天、出生后至第21天每隔3天采集一次发育中胚胎和新生儿的MRI数据库，此后每周采集一次，直至12周龄。第二，DTI可访问的非常大的数据集的采集的缓慢性将通过修改的快速自旋回波技术的组合来抵消，该技术将使采集时间减少8倍，并行成像将使时间减少2倍。第三，从胚胎第11天到成年的所有阶段的大量连续切片和染色的小鼠大脑是可用的，并且切片图像将基于常见的解剖标志被数字化捕获并弹性扭曲到MRI标准。通过本研究，将识别和分配MR可见结构。然后，通过自动“播种”算法和“神经解剖专家”手动追踪轮廓的组合，将对齐的MRI和组织学图像分割成细胞群和轴突束，所述手动追踪轮廓通过修改我们为成年小鼠大脑开发的基于Unix的3D软件进行。最后，计算神经解剖学的工具将被开发为可靠的定量测量标本之间的形态差异。该项目是通过与Moil（MRI），Sidman（神经解剖学）和米勒（计算神经解剖学）博士的合作而实现的。

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).