Cerebral Microbleeds in Traumatic Brain Injury: Their Impact on White Matter Integrity Assessed by Diffusion MRI

Dávid Bognár^1,2,3*Zalán András Petneházy^1,2,3Péter Laár^1,3,4Attila Schwarcz^1,5Tamas Peter Doczi^1,3,5Bálint Soma Környei^1,2,3Arnold Tóth^1,2,3

• ¹Medical School, University of Pécs, Pécs, Hungary
• ²Department of Medical Imaging, University of Pécs, Pécs, Hungary
• ³National Laboratory of Translational Neuroscience RRF-2.3.1-21-2022-00011, Pécs, Hungary
• ⁴University of Pécs, Pécs, Hungary
• ⁵Department of Neurosurgery, University of Pécs, Pécs, Hungary

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 3T 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.