This application is a request for funding to continue the PI's Human Brain Project research at the Stanford University School of Medicine. The research completed in the first grant period accomplished or exceeded the specific goals designated for that study. This included the development of initial software and methods for analysis of structural MRI data, and preliminary quantitative imaging studies of brain development in normal children, and children with serious brain disorders. Despite the achievements of the PI and other scientists during the first grant period, issues related to software functionality, methodology, and user-accessibility continue to impose limitations for accelerating the current pace of information acquisition in neuroimaging research. This is particularly true for neuroimaging studies focusing on the developing (pediatric) brain. To address these issues, the PI proposes to continue and expand his Human Brain Project research emphasis on three principal goals: (a) the development of innovative image processing methods, and the incorporation of these methods into an advanced platform-independent program for quantitative image analysis that will be released into the public domain; this program (currently available in alpha release) will be written in Java, a programming language that provides significant advantages for accomplishing the research goals of this project, (b) the determination of the reliability and validity of the methods and algorithms comprising this software by utilization of imaging phantoms, simulations and advanced statistical procedures and, (c) the evaluation of the utility of this software as applied to an aggregated dataset of 400 high-resolution 3D-SPGR scans collected from normal pediatric controls, and large special pediatric patient groups with serious neuropsychiatric, neurodevelopmental and neurobehavioral dysfunction. This project is designed so that the resulting software and research findings will continue to make a significant contribution to the foundation of the next generation of pediatric imaging research in neuroscience. The research proposed in this application requires expertise in the areas of software development for medical imaging, medical informatics, development and testing of advanced algorithms and methods, and quantitative analysis of image datasets obtained from normal and special pediatric populations. These needs will be addressed by an expert research team of investigators, consultants, collaborators, and staff located at Stanford and collaborating institutions.
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