Abstract
INTRODUCTION: Traumatic Brain Injury (TBI) often leads to lasting cognitive and functional deficits, with Traumatic Axonal Injury (TAI) being a significant prognostic factor. This study investigated white matter microstructural changes in moderate-to-severe TBI, focusing on the presence and number of cerebral microbleeds (MBs) using diffusion tensor imaging (DTI). MATERIALS AND METHODS: 51 participants were recruited and categorized into three groups: 17 controls, 17 TBI patients with MBs (MBP), and 17 TBI patients without MBs (MBN). Age matching was applied to minimize confounding effects. MRI scans were acquired using a 3 T Siemens MAGNETOM Prisma scanner, and DTI data were preprocessed using FSL software. Whole white matter and corpus callosum masks were reconstructed using FreeSurfer, while tractography-based methods were implemented with FSL. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted and compared across groups. Group-level voxel-wise statistical analysis was conducted using Tract-Based Spatial Statistics (TBSS), and generalized linear models (GLiMs) were applied to assess the effects of age, sex and MB number on DTI parameters. RESULTS: Significant decrease in FA (p = 0,008 - 0,042) and increases in MD (p = 0,004 - 0,016) were observed in the WM masks when comparing the MBP group with the controls. In the TBSS analysis FA (p = 0,008) and MD (p = 0,005) showed significant differences between the MBP-CON comparison, while FA (p = 0,012) and MD (p = 0,043) were significantly different between the MBP and MBN groups. Moreover, a significant FA decrease was observed in the corpus callosum when comparing the MBP and MBN groups (p = 0,007). Additionally, an increasing number of microbleeds was significantly associated with altered DTI metrics in across all white matter masks. CONCLUSION: Our findings highlight MBs as potential markers of more extensive white matter injury in moderate-to-severe TBI. The increase in MBs suggests even greater white matter damage, indicating a progression of microstructural alterations. On a global scale, tractography enhances the sensitivity in detecting structural alterations compared to traditional segmentation techniques. Examination of central white matter areas holds significant importance in uncovering the relevance of MBs.