The BRAINS program has been developed over the past fifteen years to study psychiatric and neurological disorders and has been downloaded by over 350 sites worldwide. It provides extensive tools for the analysis of brain morphology including spatial normalization, image co-registration, tissue classification, automated structure identification, surface generation, diffusion tensor analysis, and chemical shift imaging partial volume correction. Currently, the BRAINS software is the primary image processing package for 37 active grants and pending grants at The University of Iowa and 46 at outside sites. The software contains a reliable and valid image processing pipeline for analyzing brain morphology. In this proposal we will fully automate this pipeline allowing for large scale imaging studies to be rapidly analyzed. This work will build upon the integration of the ITK toolkit into the BRAINS software. We are proposing to streamline maintenance, enhance development, and make BRAINS available to a wider audience of users. The maintenance and code hardening tasks will leverage several open source tools (CMake and DART) that have been developed as part of the ITK project. This will allow the code review process to be open to users of the program. The current BRAINS user interface will be replaced with FLTK providing a native user interface across Windows, Macintosh and Unix/Linux based platforms. To evaluate BRAINS and several other neuroimaging software applications a unique multi-center dataset that has been collected by the MIND Institute will be used to measure intra- and inter-site reliability as well as validity of these tools.