Approximately 14% of school age children with mild traumatic brain injury (TBI) including sports-related concussions (SRC) remain symptomatic 3 months after injury (1-2). We and others have previously shown regions of cortical and subcortical hypoperfusion using manual region of interest analysis in symptomatic patients in the chronic phase of mild TBI (3-6); however data in the pediatric population remains limited. The purpose of this study was to use whole-brain spatial mapping and a voxel-wise statistical approach to investigate the extent and anatomical distribution of cerebral hypoperfusion in chronic symptomatic pediatric SRC subjects.Twenty three adolescents (15 ± 3 years) who sustained a SRC (3–24 months before imaging) and 13 controls (15 ± 3 years) were enrolled in the study. Pediatric SRC subjects were referred by a pediatric neurologist and included if they self-reported cognitive, behavioral, or emotional symptoms. Conventional 3D T1 weighted (MPRAGE, repetition time (TR) and echo time (TE) = 1950 msec and 2.26 msec, 1 mm slice thickness, field of view (FOV; 230 x 256 mm) and DSC-PWI (SE-EPI, TR/TE = 2580/32 ms, flip angle = 90º, 5 mm slice thickness, FOV = 128 x 128, and 50 measures) were acquired using a 3.0T Siemens Tim Trio MR scanner equipped with a 12 channel receive-only head coil. For the DSC-PWI acquisition, gadolinium contrast (gadodiamide, Omniscan, GE Healthcare Inc., Princeton, NJ) was administered intravenously (0.1 mmol/kg). Relative CBF maps were generated using Olea Sphere (Olea Medical, Cambridge, MA, USA) using a Bayesian probabilistic estimation algorithm with automatic arterial input function selection. The pre-injection DSC images were averaged together and then deformably registered to the T1w image using ANTs (7). The T1w image was then deformably registered to a T1w template that we had constructed from 20 patients and controls. These two transformations were used to warp the rCBF maps into the common template space for comparison. Segmentation was performed using ANTs to identify the cortex, thalamus, and other structures. Using the Randomise tool in FSL(8), voxel-wise analysis of the cortex was performed using nonparametric permutation testing with correction for family-wise error and threshold-free cluster enhancement, where highlighted cluster represent areas where perfusion differences are significant at p < 0.05. Statistical differences in mean thalamus CBF were determined using an independent samples t- test where p < 0.05 was considered significant.Cluster voxel-wise analysis of the CBF data identified multiple areas of reduced CBF incorporating both the cerebral cortex and subcortical regions. The most prominent regions included the left medial temporal gyrus and left inferior frontal lobe (Figure 1 A-C) with smaller clusters of hypoperfusion seen in the left posterior frontal lobe and posterior cingulate cortex (Figure 1 D-F; p < 0.05). In the thalamus, the SRC subjects also showed reduced CBF compared to controls (Figure 2; p = 0.008).Findings of cortical and subcortical regions of reduced CBF suggest widespread regions of hypoperfusion in chronic symptomatic pediatric SRC subjects. We speculate that hypoperfusion in the temporal lobe, posterior cingulate cortex and thalamus may be implicated in cognitive deficits in these subjects. Compared to our previous results (6) using region of interest analysis, we detected a greater number of areas of hypoperfusion suggesting that the use of whole-brain spatial mapping and voxel-wise analysis improved detection of CBF abnormalities.