Magnetic susceptibility of the hippocampal subfields and basal ganglia in acute mild traumatic brain injury
Authors: Essex Christi A. , Bedggood Mayan J. , Merenstein Jenna L. , Morgan Catherine , Murray Helen C. , Holdsworth Samantha J. , Faull Richard L. M. , Hume Patria , Theadom Alice , Pedersen Mangor 
Published: January 2025

Despite vulnerability to microstructural tissue damage following mild traumatic brain injury (mTBI), key subcortical brain regions have been overlooked in quantitative susceptibility mapping (QSM) studies. Alterations to tissue composition in the functionally and structurally distinct hippocampal subfields and basal ganglia regions may reflect distinct symptomatology, and better characterisation of these regions is needed to in-crease our understanding of mTBI pathophysiology. To address this issue, we used magnetic source-separated QSM to quantify spatial distributions of positive (iron-related) and negative (myelin-, protein-, and calcium-related) magnetic susceptibility across 10 hippocampal substructures and 16 segmentations of the basal ganglia in 25 male participants with acute (< 14 days) sports-related mTBI (sr-mTBI). Additional variables of interest including age, injury severity, and days since injury at time of the magnetic resonance imaging (MRI) scan were also correlated with both positive and negative susceptibility values. Primary analyses indicated no significant difference in positive susceptibility values between sr-mTBI participants and controls for hippocampal and basal ganglia ROIs. For negative sign values, susceptibility was significantly less negative for sr-mTBI participants in the cornu ammonis 4 (CA4) region only (pFDR < 0.05). In line with the known linear relationship between iron deposition and age in deep grey matter sites, particularly within the first three decades of life, significant positive relationships were observed between positive susceptibility and age in the putamen, caudate, red nucleus, parabrachial pigmented nucleus, and ventral pallidum (pFDR < 0.05). Positive relationships were also observed between absolute negative susceptibility values and age in the hippocampal fimbria, caudate, and extended amygdala (pFDR < 0.05), suggesting age-related calcifications in these regions. A negative relationship was observed between negative absolute values and age in the ventral pallidum (pFDR < 0.05), indicating potential changes to myelin content in this region. No significant associations were observed be-tween any other variable and signed susceptibility values. The results of this study contribute to, and extend, prior literature regarding the temporal kinetics of biomagnetic substrates as a function of ageing. Decreased negative susceptibility after mTBI in the CA4 region also suggests potential injury-related effects on myelin content or cell loss; a particularly interesting finding in light of the well-established vulnerability of this region to pathology in chronic traumatic encephalopathy (CTE). The lack of other significant between-group differences suggest that alterations to tissue content may not be quantifiable at the acute stage of injury in subcortical ROIs or may be masked by age-related tissue susceptibility changes as a common feature across all participants in this young cohort. Future research should consider the use of longitudinal study designs to mitigate the potential influence of these factors.