Background: In traumatic brain injury, axonal damage is a major pathophysiological process and may be a primary cause of adverse neurological outcomes. However, traumatic axonal injury and its effects on brain functional connectivity are very difficult to directly detect and quantify in living patients. Diffusion tensor imaging (DTI) appears to have great promise with regard to detecting axonal injury. Resting-state fMRI correlation analysis likewise may be a powerful and broadly applicable method for investigating brain functional connectivity. In our preliminary studies, these two techniques have been successfully used together in several civilian TBI patients. They appear to synergistically cross validate each other; disrupted functional connectivity underlying focal neurological deficits were revealed using resting-state fMRI correlation analysis while DTI demonstrated the axonal injury responsible for the disruptions. Conventional MRI and CT entirely failed to explain many of these deficits. This cross validation is important as it adds confidence to the interpretation of the results. Without resting-state fMRI correlation analysis, the consequences of apparent axonal injury on DTI for the functional connectivity of the brain may not be clear; the axonal injury could be in white matter tracts that are redundant, or not severe enough to be functionally important. Without DTI, the cause of a disruption in connectivity seen using resting-state fMRI correlation analysis will likewise not always be known; processes other than traumatic axonal injury could be responsible. Both of these advanced techniques along with a full conventional MRI can be performed on standard clinical MRI scanners in approximately 45 minutes per patient. Apart from in our preliminary studies, resting-state fMRI and DTI have not been used together to investigate traumatic brain injury.