Development of 3D electronic atlases of deveoping mouse brains

开发小鼠大脑发育的 3D 电子图谱

• 批准号: 8248494
• 负责人: hangyi jiang
• 金额: $ 14.1万
• 依托单位: ANATOMYWORKS, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-10 至 2014-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248494
• 关键词: Adult; Agreement; Anatomy; Animals; Atlases; Brain; Brain Pathology; Cells; Chemicals; Communities; Computer software; Consult; Copyright; Data; Databases; Development; Devices; Electrodes; Electronics; Embryo; Engineered Gene; Ensure; Feedback; Goals; Head; Histology; Image; Individual; Investigation; Label; Licensing; Location; Magnetic Resonance Imaging; Manuals; Marketing; Measurement; Measures; Morus; Mus; Needles; Neuraxis; Neurosciences; Phase; Population; Positioning Attribute; Primates; Process; Reading; Research; Research Design; Resources; Role; Schedule; Slice; Source; Staging; Structure; System; Technology; Testing; Transplantation; Work; Writing; base; blind; cranium; design; in vivo; interest; mouse model; mutant; neonate; operation; phase 2 study; product development; programs; sample fixation; software development; stem; two-dimensional; vector; virtual

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.

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操作的电子鼠标图册。在基于小鼠的神经科学研究中，立体定位操作是一项重要技术，其中化学物质、载体、细胞或电极被递送到特定的感兴趣的大脑结构。由于分娩本质上是一种盲操作，因此立体定位图谱是研究的重要资源。目前，Paxinos atlas 几乎专门用于此目的。然而，该地图集有一些局限性。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。其次，它是基于组织学的二维图谱。根据二维信息设计倾斜的针路以避免损坏重要的大脑结构几乎是不可能的。第三，固定和切片过程导致大脑坐标不准确。第四，该图谱的每个切片方向都基于一只动物。因此，不考虑个体小鼠大脑之间的解剖变异性。 在这个项目中，我们将推出全三维的鼠标电子图谱 处于不同发育阶段的大脑进行图像引导立体定位操作。由于立体定位操作的坐标是基于颅骨上的解剖标志，因此联合配准的CT（针对颅骨结构）和MRI（针对脑结构）数据确保了准确的坐标系。大脑解剖结构基于多只小鼠的体内 MRI，提供了未扭曲（未固定且未切片）大脑解剖结构的群体代表性解剖结构。我们的AtlasGuide软件提供各种先进功能，例如用于术前规划的“虚拟针路”和斜角针引导。目前，我们正在与 Stoelting 签订产品开发协议。在第一阶段的应用中，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的测试，但要编写该具有多种功能的产品的手册需要付出相当大的努力。目前，手册是产品介绍中唯一缺失的部分。为此，我们将编写一份综合手册，并与 Stoelting 合作进行产品介绍。目标 2：开发用于高级图像引导操作的用户界面 在这个目标中，我们将实现一个新功能、基于地标的定位系统，这将是目标 3 和第二阶段研究的关键功能。目标 3：实现读取用户定义的 MR 图像的功能 这一新功能将允许用户加载自己的 MRI 数据。这对于使用大脑解剖结构发生改变的小鼠模型（例如突变体）或其他物种（例如灵长类动物）的大脑的用户来说尤其重要。 公共卫生相关性：我们将开发名为 AtlasGuide 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。此类研究对于研究大脑如何工作和理解大脑病理机制非常重要。