Mild traumatic brain injury (mTBI) is a growing public health problem. Most patients recover quickly, but some patients may suffer from serious neurological, behavioral, and cognitive symptoms¹. However, our understanding of the underlying pathophysiology associated with mTBI is limited. In this study, we investigated white matter (WM) changes in mTBI in terms of compartment specific WM tract integrity (WMTI) metrics^2,3 derived from diffusion kurtosis imaging (DKI), such as intra-axonal diffusivity (D_axon), extra-axonal axial and radial diffusivities (D_e,a and D_e,r), and axonal water fraction (AWF).We studied 17 patients with mTBI (mean age, 36 ± 11, range 24 - 64 yrs; 8 male) within 2 weeks of injury and 16 normal controls (NC) (mean age, 32 ± 8, range 19 - 50 yrs; 9 male). MR imaging was performed on a 3T MR scanner (Skyra, Siemens). DKI acquisition was performed with 6 b-values (0, 0.25, 1, 1.5, 2,2, 2.5 ms/µm²) along with 3,6,20,20,30,60 diffusion encoding directions using multiband (factor of 2) echo-planar imaging for accelerated acquisitions. Other imaging parameters were: acquisition matrix = 88 × 88, image resolution = 2.5 × 2.5 × 2.5 mm³, number of slices = 56, TR/TE = 4.9s/95ms, BW/pixel = 2104Hz, FOV = 220 × 220 mm², a GRAPPA factor of 2. Both diffusion and kurtosis parametric maps of mean, axial and radial diffusion coefficients (MD, AD, RD), fractional anisotropy (FA), and mean, axial and radial kurtosis (MK, AK, RK) were calculated, and then used to derive WM tract integrity of D_axon, D_e,a, D_e,r and AWF. We performed tract-based spatial statistics (TBSS)⁴ with age and gender as covariates to test differences between NC and mTBI groups. The resulting statistical maps from TBSS were thresholded (p < 0.05).Fig. 1 shows the percentage of significantly different voxels between NC and mTBI from the TBSS analysis. We found that the most sensitive metrics were D_axon and D_e,a. Fig. 2 shows the corresponding spatial distribution of the TBSS analysis for these two metrices, particularly in the splenium of corpus callosum (sCC). In the sCC, significantly decreased values in the mTBI group were found in D_axon = 1.18 ± 0.05, 1.11 ± 0.07 and D_e,a = 2.85 ± 0.07, 2.73 ± 0.13; NC vs mTBI, respectively.In this study, we demonstrate that WMTI metrics can detect widespread WM changes after mTBI. We observed: 1) decreased D_axon and D_e,a in mTBI subjects; and 2) WM changes particularly in the sCC. These changes are all in line with acute axonal injury, with axonal beading⁵ as a possible mechanism providing main restrictions to the diffusion in the intra-axonal space, thereby modulating the diffusivity mainly inside, but also outside along axons in the acute phase after mTBI.This study indicates that WMTI metrics may be useful as early biomarkers of injury after mTBI. The observed decreases in D_axon and D_e,a suggest that increased restrictions along the axons, both inside and outside, such as possible axonal beading, could occur acutely after injury. Detecting and understanding WM injury after mTBI is critical for further investigating the mechanisms that underlie tissue damage and recovery. Longitudinal follow-up may provide insight in the different acute and chronic processes altering WM after mTBI.