Characterizing Positive and Negative Quantitative Susceptibility Values in the Cortex Following Mild Traumatic Brain Injury: A Depth- and Curvature-Based Study

Abstract

Evidence has linked head trauma to increased risk factors for neuropathology, including mechanical deformation of the sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau adjacent to these spaces related to chronic traumatic encephalopathy. However, little is known about microstructural abnormalities and cellular dyshomeostasis in acute mild traumatic brain injury in humans, particularly in the cortex. To address this gap, we designed the first architectonically motivated quantitative susceptibility mapping study to assess regional patterns of net positive (iron-related) and net negative (myelin-, calcium-, and protein-related) magnetic susceptibility across 34 cortical regions of interest following mild traumatic brain injury. Bilateral, between-group analyses sensitive to cortical depth and curvature were conducted between 25 males with acute (<14 d) sports-related mild traumatic brain injury and 25 age-matched male controls. Results suggest a trauma-induced increase in net positive susceptibility focal to superficial, perivascular-adjacent spaces in the parahippocampal sulcus. Decreases in net negative susceptibility values in distinct voxel populations within the same region indicate a potential dual pathology of neural substrates. These mild traumatic brain injury-related patterns were distinct from age-related processes revealed by correlation analyses. Our findings suggest depth- and curvature-specific deposition of biological substrates in cortical tissue convergent with features of misfolded proteins in trauma-related neurodegeneration.