Development of 3D electronic atlases of deveoping mouse brains

描述（由申请人提供）：本申请的总体目标是开发用于图像引导立体定位手术的电子鼠标图谱。在基于小鼠的神经科学研究中，立体定位操作是一项必不可少的技术，其中化学物质，载体，细胞或电极被递送到感兴趣的特定大脑结构。由于分娩基本上是一个盲目的操作，立体定位地图集是研究的重要资源。目前，Paxinos地图集几乎完全用于这一目的。然而，该地图集有几个局限性。首先，它只涵盖成人大脑，目前还没有适用于新生儿大脑的立体定位图谱。第二，它是一个基于组织学的二维图谱。基于2D信息来设计倾斜的针路径以避免损伤重要的脑结构几乎是不可能的。第三，固定和切片过程在大脑坐标中引入了不准确性。第四，图谱基于每个切片方向的一只动物。因此，不考虑个体小鼠大脑之间的解剖变异性。 在本计画中，我们将介绍全立体的滑鼠电子地图集 不同发育阶段的大脑进行图像引导立体定位手术。由于立体定位操作的坐标基于颅骨上的解剖标志，因此共配准的CT（用于颅骨结构）和MRI（用于脑结构）数据确保了精确的坐标系。脑解剖结构基于多只小鼠的体内MRI，提供未变形（未固定且未切片）脑解剖结构的群体代表性解剖结构。我们的软件，MANAGASGuide，提供各种先进的功能，如“虚拟针路径”的术前规划和针的角度指导。目前，我们正在与Stoelting签订产品开发协议。在第一阶段的申请中，我们将实现以下三个目标。目标1：编写手册并介绍第一个产品虽然第一个产品已经完成并经过严格测试，但具有广泛功能的该产品的手册制作需要相当大的努力。目前，手册是产品介绍中唯一缺少的部分。为此，我们将编写一份全面的手册，并与Stoelting合作进行产品介绍。目标二：为先进的影像引导操作开发用户界面在本目的中，我们将实施一个新功能，即地标定位系统，这将是目的3和第II阶段研究的主要功能。目标3：实现读取用户定义的MR图像的功能。该新功能将允许用户加载自己的MRI数据。这对于使用具有改变的大脑解剖结构（例如突变体）的小鼠模型或其他物种（例如灵长类动物）的大脑的用户尤其重要。 公共卫生相关性：我们将开发一个名为“健康指南”的软件。这使得能够在不同发育阶段将针或电极准确插入小鼠大脑。这种类型的研究对于研究大脑如何工作和了解大脑病理机制非常重要。

DESCRIPTION (provided by applicant): The overall goal of this application is to develop electronic mouse atlases for image-guided stereotaxic operations. In mouse-based neuroscience studies, stereotaxic operations are an essential technology, in which chemicals, vectors, cells, or electrodes are delivered to specific brain structures of interest. Because the delivery is essentially a blind operation, stereotaxic atlases are an essential resource of the studies. Currently, Paxinos atlas is almost exclusively used for this purpose. However, this atlas has several limitations. First of all, it covers only adult brains and at present there is no stereotaxic atlas available for neonate brains. Second, it is a histology-based two-dimensional atlas. It is almost impossible to design an oblique needle path to avoid damaging important brain structures based on the 2D information. Third, the fixation and sectioning process introduced inaccuracy in the brain coordinates. Forth, the atlas is based on one animal for each sectioning orientation. Therefore, anatomical variability among individual mouse brains is not considered. In this project, we will introduce fully three-dimensional electronic atlases of mouse brains at different developmental stages for image-guided stereotaxic operations. Because the coordinates of stereotaxic operations are based on anatomical landmarks on the skull, co-registered CT (for skull structures) and MRI (for brain structures) data ensure the accurate coordinate systems. The brain anatomy is based on in vivo MRI of multiple mice, providing the population-representative anatomy of the undistorted (not fixed and not sectioned) brain anatomy. Our software, AtlasGuide, provides various advanced functions such as "virtual needle path" for pre-operation planning and oblique-angle needle guidance. Currently, we are in the process of product development agreement with Stoelting. In this phase I application, we will perform following three aims. Aim 1: To write a manual and introduce the first product While the first product is already completed and rigorously tested, the manual making of this product with a wide array of features requires a considerable amount of effort. Currently, the manual is the only missing piece for the product introduction. In this aim, a comprehensive manual will be written and we will work with Stoelting for the product introduction. Aim 2: To develop user-interface for advanced image-guided operations In this Aim, we will implement a new feature, landmark-based positioning system, which will be a key function for Aim 3 and the Phase II study. Aim 3: To implement a function to read user-defined MR images This new function will allow users to load their own MRI data. This will be especially important for users using mouse models with altered brain anatomy (e.g. mutants) or brains of other species such as primates. PUBLIC HEALTH RELEVANCE: We will develop software called AtlasGuide. This enables accurate needle or electrode insertion to mouse brains at different developmental stages. This type of studies is important to investigate how brain works and understand mechanisms of brain pathology.