Distribution of paramagnetic and diamagnetic cortical substrates following mild Traumatic Brain Injury: A depth- and curvature-based quantitative susceptibility mapping study

Evidence has linked head trauma to increased risk factors for neuropathology, including acute mechanical deformation of the cortical sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau (p-tau) adjacent to these spaces related to chronic traumatic encephalopathy (CTE). Despite this, little is known about microstructural abnormalities and cellular dyshomeostasis at the acute stage of mild traumatic brain injury (mTBI) in humans, particularly in the cortex. To address this gap in the literature, we designed the first architectonically-motivated quantitative susceptibility mapping (QSM) study to assess regional patterns of positive (iron-related) and negative (myelin-, calcium-, and protein-related) magnetic susceptibility in cortical regions of interest (ROI) following mTBI. Depth- and curvature-specific positive and negative QSM values were compared between 25 males with acute (< 14 days) sports-related mTBI (sr-mTBI) and 25 age-matched male controls across 34 cortical ROIs. Bilateral between-group analyses were conducted on specific ROI curvature bins (crown, bank, and fundus) as well as a combined curvature measure, across 21 cortical depths, for each ROI. Correlations between positive and negative susceptibility were analysed for age, brain injury severity, and the number of days since injury. We observed significant group differences in magnetic susceptibility for depth, curvature, and ROIs. Our results suggest a trauma-induced pattern of iron deposition preferential to superficial, perivascular-adjacent spaces in the sulci of the parahippocampal gyrus. Co-localised decreases in diamagnetism in the same region suggest dual pathology of neural substrates, the biological mechanisms behind which remain speculative. Significant correlations were found between magnetic susceptibility and age, both in ROIs and cortical depths distinct from those showing sr-mTBI-related differences. Little to no relationship was observed between magnetic susceptibility and subjective markers of injury or injury latency. The coherence between our findings and pathognomonic patterns of misfolded proteins in trauma-related neurodegeneration is interesting, which may have implications for the role of brain iron in microstructural cortical tissue damage after a mild brain injury. Further longitudinal research is needed to elucidate the long-term implications of our findings.