Development of 3D electronic atlases of deveoping mouse brains

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 exclusivelyused 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 eachsectioning 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 isbased 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 positioningsystem, 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.