Study of fiber anatomy in mouse development via MRI/DTI

描述(申请人提供)：这个项目的主要目标是描述小鼠大脑的发育，重点是脑白质解剖，使用磁共振显微成像结合数学方法进行定量图像分析。传统上用于检查小鼠脑切片的组织学方法受到组织变形或丢失、难以从切片构建空间一致的体积图像、准备工作广泛以及缺乏对小鼠脑的活体检查的能力的限制。磁共振成像(MRI)作为一种与组织学优势互补的技术正在兴起，就这些局限性而言。在这个项目中，我们将开发小鼠大脑的成像和分析方法，并将使用它们来生成C57BL/6J小鼠品系的脑发育的规范数据。我们的重点将是使用扩散张量成像(DTI)来表征白质的结构。在人脑项目几个小组目前工作的基础上，我们建议开发计算解剖学的数学方法，这些方法主要在两个方面补充传统的分析方法。首先，他们可以识别非常微妙和局部的形状特征，而不需要事先知道受影响的大脑区域的位置。其次，它们是高度自动化和定量的，因此能够使用统计图像分析技术，以最小的努力检查大量动物。我们的图像分析方法将涉及用于小鼠脑结构重建和空间归一化的形状分析方法，并将利用成熟的立体定位空间分析框架。在将MRI图像保持质量的空间归一化到各自发育阶段的立体定位空间后，将在若干不同的发育阶段测量灰质和白质结构的正常解剖变异。这些标准化数据将对后续的DTI研究有用，这些研究旨在通过寻找超出正常范围的区域来识别神经遗传学小鼠的异常发育区域。我们将在EMX-1基因敲除小鼠的初步研究中测试这一方法，EMX-1基因敲除小鼠是一种特征良好的品系，具有异常的皮质层和脱束的白质纤维束，包括胼胝体，我们将使用组织切片来验证我们基于MR的测量。

DESCRIPTION (provided by applicant): The main goal of this project is to characterize the development of the murine brain, with emphasis on white matter anatomy, using magnetic resonance micro-imaging in conjunction with mathematical methodologies for quantitative image analysis. The traditionally used histological methods for examination of murine brain sections are limited by tissue distortion or loss, by difficulties in constructing a spatially consistent volumetric image from sections, by extensive effort in preparation, and by lack of capability for in vivo examination of the mouse brain. Magnetic resonance imaging (MRI) is emerging as a technology with strengths complementary to histology, with respect to these limitations. In this project, we will develop methods for imaging and analysis of the murine brain, and we will use them to generate normative data for brain development of the C57BL/6J mouse strain. Our emphasis will be on using diffusion tensor imaging (DTI) to characterize the white matter architecture. Building upon current work by several groups in the Human Brain Project, we propose to develop mathematical methodologies for computational anatomy, which complement traditional analysis methods in mainly two ways. First, they can identify very subtle and localized shape characteristics, without the need to know the location of an affected brain region a priori. Second, they are highly automated and quantitative, thus enabling the examination of a large number of animals with minimal effort, using statistical image analysis techniques. Our image analysis methodology will involve shape analysis methods for the reconstruction and spatial normalization of murine brain structures, and it will utilize the well-established framework of stereotaxic space analysis. After mass-preserving spatial normalization of MRI images to a stereotaxic space of the respective developmental stage, the normal anatomic variation of grey and white matter structures will be measured at a number of different developmental stages. This normative data will be useful in subsequent DTI-based studies aiming to identify regions of abnormal development in neurogenetic mice, by finding regions that fall outside this normal range. We will test this methodology on a pilot study of the Emx-1 knockout mouse, a well-characterized strain with abnormal cortical lamination and defasciculated white matter fiber tracts, including the corpus callosum, and we will validate our MR-based measurements using histological sections.