This work focuses on aspects of diffusion tensor imaging (DTI) tractography; in particular, we have done novel work in creating and validating tractography methods and in applications to areas of imaging genetics and white matter pathology. We have introduced a fluid mechanics based DTI tractography method for estimating the most likely connection paths between points in diffusion tensor imaging volumes, based on conventional single tensor and tensor distribution function reconstruction frameworks, which extends previous approaches. We have created both digital and anatomic human validation resources for DTI tractography methods and for point to point comparison of diffusion imaging signal or analysis results with underlying histology. We have created novel approaches for the analysis of the heritability of white matter structure through large scale diffusion imaging studies involving twins using DTI alone and in multimodal imaging of functional networks using both fMRI and DTI. Finally, we have investigated several applications of DTI tractography analysis to the study of the pathophysiology of aspects of common WM pathologies, such as schizophrenia and cerebellar ataxia.