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Project Goals

Goal 1: We will produce a multi-modal high resolution neuroanatomical and white matter connectivity atlas of the C57BL/6J brain: We will extend the existing Mouse Atlasing Project (MAP) C57BL/6J anatomical atlas to map the adult mouse central nervous system at high resolution and to encompass cellular morphology, the cytoarchitecture at the level of individual cells, and the major neural tracts of the brain. Neuroimaging data will include Magnetic Resonance Imaging (MRI) structural imaging and high angular diffusion-weighted imaging (DTI/HARDI). The HARDI data will significantly extend the number of diffusion directions that exist in presently available diffusion atlases of the adult mouse brain. Fluorescent blockface imaging will provide high-resolution images with detailed contrast for use in 3D modeling as well as aiding in cross-modal co-registration. Detailed histological data, in the form of classical histology and immunohistochemistry will be acquired at cellular-level resolution in all 3 major planes of section. Having microscopy, blockface, and MR imaging data in the same animals will enable us to perform confirmatory analyses of tractography results against histologically derived white matter pathways. Spherical harmonic decomposition of diffusion data, in addition to traditional measures of preferred fiber orientation, will provide detailed geometric assessment of regional fiber crossings and white matter integrity.

Goal 2: We will systematically align all MR imaging data, histological sections, and tractography results into known mouse atlas frameworks: We will develop efficient routines to warp the C57BL/6J mouse brain atlas into other commonly used brain atlas frameworks, e.g. the Allen Reference Atlas (ARA). We will enable these data to also encompass the entire transcriptome of brain expressed genes by taking advantage of direct linkage to the Allen Reference Atlas and other online genomic resources. The LONI Pipeline workflow environment will be employed to construct highly optimized data processing streams that utilize the LONI computational grid. The atlases, accompanying data, and workflows used will be archived and made openly available to the community. Annotated, full resolution images will also be available through MBAT, a sophisticated data visualization and integration application under Goal 3.

Goal 3: We will extend development of intuitive and integrative software tools to assist the dissemination, understanding, and interpretation of the vast amounts of imaging data and resulting connectivity information to be produced under this project: We will significantly enhance tools for the facile manipulation and analysis of mouse histological and MR imaging data. We will make user interactions with these atlas data simple and intuitive using the Mouse Brain Atlasing Toolkit (MBAT), enhancing MBAT to permit interaction between the acquired connectivity atlas and the large number of genomic efforts that are available on the Internet. We will enable users to examine gene expression (e.g. via GENSAT, etc) within and between neuroanatomically defined regions conditionalized by connectivity. Thus, the anatomical and connectivity information can be used to assess systems-wide levels of gene expression in mouse models of disease affecting connectivity, e.g. Parkinson’s, Multiple Sclerosis, and Alzheimer’s disease (AD).