IntroductionMild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS).Materials and methodsChildren aged 8–16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons.ResultsNo significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group.ConclusionsPost-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

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In the largest sample studied to date, white matter microstructural trajectories and their relation to persistent symptoms were examined after pediatric mild traumatic brain injury (mTBI). This prospective, longitudinal cohort study recruited children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) from five pediatric emergency [Correction added on 04 May 2022, after first online publication: Quynh Doan's affiliation is updated and subsequent affiliations were re-numbered.]

Background: Motion can compromise image quality and confound results, especially in pediatric research. This study evaluated qualitative and quantitative approaches to motion artifacts detection and correction, and whether motion artifacts relate to injury history, age, or sex in children with mild traumatic brain injury or orthopedic injury relative to typically developing children. The concordance between qualitative and quantitative motion ratings was also examined.Method: Children aged 8-16 years with mild traumatic brain injury (n=141) or orthopedic injury (n=73) were recruited from the emergency department and completed an MRI scan roughly 2 weeks post-injury.Typically developing children (n=41) completed a single MRI scan. T1-and diffusion-weighted images were visually inspected and rated for motion artifacts by trained examiners. Quantitative estimates of motion artifacts were derived from FreeSurfer and FSL.Results: Age (younger > older) and sex (boys > girls) were signi cantly associated with motion artifacts on both T1-and diffusion-weighted images. Children with mild traumatic brain or orthopedic injury had signi cantly more motion-corrupted diffusion-weighted volumes than typically developing children, but mild traumatic brain injury and orthopedic injury groups did not differ from each other. The exclusion of motion-corrupted volumes did not signi cantly change diffusion tensor imaging metrics.Discussion: Results indicate that automated quantitative estimates of motion artifacts, which are less labour-intensive than manual methods, are appropriate. Results have implications for the reliability of structural magnetic resonance imaging research and highlight the importance of considering motion artifacts in studies of pediatric mild traumatic brain injury.

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Highlights We examined white matter microstructure after pediatric mTBI using NODDI and DTI. Children with mTBI did not significantly differ from those with OI on any metrics. Minor alterations, if any, may be present in children at the post-acute stage after mTBI. Large longitudinal studies are needed to understand long-term brain changes post injury.

Background: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI). Methods: Children (mTBI n=320, OI n=176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons. Results: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample. Conclusions: Overall, there were no differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with only relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed.