Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software.