RESEARCH ARTICLE Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods Naomi J. Goodrich-Hunsaker 1 | Tracy J. Abildskov 1 | Garrett Black 2 | Erin D. Bigler 1 | Daniel M. Cohen 3 | Leslie K. Mihalov 3 | Barbara A. Bangert 4 | H. Gerry Taylor 5 | Keith O. Yeates 6 1 Department of Psychology, Brigham Young University, Provo, Utah 2 Ohio State University Fisher College of Business, Columbus, Ohio 3 Division of Emergency Medicine, Nationwide Children’s Hospital, Columbus, Ohio 4 Department of Radiology, Case Western Reserve University School of Medicine, Cleveland, Ohio 5 Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, Ohio 6 Department of Psychology, University of Calgary, Calgary, Alberta, Canada Correspondence Keith O. Yeates, Department of Psychology, University of Calgary, 2500 University Dr. NW, AD254 Calgary, Alberta, T2N 1N4, Canada., Email: kyeates@ucalgary.ca Funding Information National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Predicting Outcomes in Children with Mild Traumatic Brain Injury, 1R01HD076885. Abstract Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8–15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identify- ing group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age- related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sen- sitivity and better tract-specific results for identifying developmental and sex-related differences within the brain. KEYWORDS diffusion tensor imaging, mild traumatic brain injury, pediatric, development, white matter integrity 1 | INTRODUCTION There are several different quantitative imaging analysis techniques that can be applied to diffusion-weighted imaging as measures of white matter integrity. As with all techniques, the goal of any neuroimaging outcome study is to generate quantifiable measurement of brain devel- opment, disease, damage, or degeneration that not only is sensitive in detecting clinically significant differences but also can account for non- injury or disease variables such as age and sex. To achieve this goal, any technique must be sufficiently sensitive at detecting clinical abnor- malities. This is especially critical in populations like mild traumatic brain injury (mTBI), where pathology, when present, is likely to be subtle (Aoki & Inokuchi, 2016; Fink, Mogil, & Lipton, 2016; Hulkower, Poliak, Rosenbaum, Zimmerman, & Lipton, 2013). mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to early adulthood is also a time period of tremendous developmental changes in the brain, where diffusion tensor imaging (DTI) metrics reflect both dynamic age- J Neuro Res. 2017;1–16. wileyonlinelibrary.com/journal/jnr V C 2017 Wiley Periodicals, Inc. | 1 Received: 31 March 2017 | Revised: 28 July 2017 | Accepted: 28 July 2017 DOI: 10.1002/jnr.24142