Impaired Glymphatic Function in Diffuse Axonal Injury: Evaluation Using the Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Method

PURPOSE: Glymphatic system impairment has been suggested in previous animal and human studies regarding traumatic brain injury (TBI). Diffuse axonal injury (DAI) is an important pathological feature of TBI and is frequently diagnosed in patients with moderate to severe TBI. This study evaluated the glymphatic system function in patients with DAI using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), a non-invasive technique. METHODS: A total of 162 patients with TBI, including 84 with DAI and 78 without DAI, underwent MRI with DTI within 6 months of the date of injury. The ALPS index was calculated to assess the glymphatic system activity and compared between patients with and without DAI. Analysis of covariance (ANCOVA) was used to compare the ALPS index between patients with DAI grades 1, 2, and 3. Correlation analysis was performed between the ALPS index, DAI grade, and Glasgow Coma Scale (GCS) score. RESULTS: Patients with DAI (1.29 ± 0.17) had a significantly lower ALPS index than those without DAI (1.42 ± 0.19, P < 0.001). The ALPS index differed significantly between patients with different DAI grades (ANCOVA, P < 0.001). The ALPS index and DAI grades were negatively correlated (r =-0.47, P < 0.001). The ALPS index and GCS scores showed a weak positive correlation (r = 0.174, P = 0.027). CONCLUSIONS: Patients with DAI have a lower ALPS index, indicating impaired glymphatic system activity, which is more severe in patients with a higher DAI grade. These findings broaden the understanding of the pathophysiology of DAI and help predict patients' prognoses and recovery trends.