In patients with Medial Temporal Lobe Epilepsy (MTLE), more severe impairment in the ipsilateral than the contralateral hemisphere white matter tracts, including Superior Longitudinal Fasciculus (SLF), are demonstrated on diffusion tensor imaging (DTI). Many clinicians and researchers conclude that drawing regions of interest (ROI) in the white matter can demonstrate these asymmetries. In this study we demonstrate that fractional anisotropy (FA) values derived from manually drawing ROI's on diffusion tensor imaging (DTI) of SLF differ between the side of seizure onset compared to the contralateral side in each individual patient with MTLE does not demonstrate these previous conclusions. We therefore believe that clinicians should recognize that this method of measurement can be inaccurate and should not be interpreted independently.