Quantifying Iron Accumulation in Deep Gray Matter Nuclei of Patients with Mild Traumatic Brain Injury Using Quantitative Susceptibility Mapping: A Comparative Study with Healthy Controls

Abstract

Background: Mild traumatic brain injury (mTBI) is a common neurological condition characterized by subtle brain dysfunction. Although generally considered less severe than moderate and severe TBI, it can have significant consequences on cognitive and motor function. Iron deposition in the basal ganglia nuclei, particularly in individuals with mTBI, has been reported as a potential biomarker for neurodegenerative and neurocognitive changes following injury. While previous studies have explored the relationship between iron deposition and mTBI, few human studies have examined these changes using quantitative susceptibility mapping (QSM). The QSM is a powerful technique that enables the non-invasive measurement of iron content in deep brain structures, providing valuable insights into the pathophysiology of mTBI. Objectives: This study aimed to compare magnetic susceptibility values (iron content) in the deep gray matter (DGM) nuclei regions of patients with mTBI and healthy controls (HCs). Patients and Methods: In this case-control study, we enrolled 10 acute mTBI patients and 10 age-matched HCs who underwent imaging with a 3 Tesla Prisma scanner magnetic resonance imaging (MRI), including T1 weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) and multi-echo 3D gradient-recalled echo (GRE) sequences for QSM reconstruction. Inclusion criteria included patients aged 16 - 50 years, a Glasgow Coma Scale (GCS) score of 13 - 15 upon emergency department arrival, and a history of loss of consciousness for less than 30 minutes. Exclusion criteria included prior brain injuries, neurological disorders, psychiatric conditions, or substance abuse. The magnetic susceptibility of the DGM nuclei was calculated using the streaking artifact reduction for QSM (STAR-QSM) technique. Group comparisons were performed using independent t-tests. Results: Significantly higher magnetic susceptibility values were observed in the DGM nuclei regions, specifically in the right caudate (P < 0.001), left caudate (P = 0.002), right thalamus (P = 0.004), and right hippocampus (P = 0.002), in mTBI patients compared to HCs. Conclusion: These findings suggest that mTBI may be associated with alterations in iron content or magnetic susceptibility within the DGM nuclei regions compared to HCs, potentially reflecting microstructural changes. This study provides preliminary evidence for the potential of QSM as a tool for investigating tissue susceptibility in acute mTBI. Future research should focus on longitudinal studies with larger sample sizes to examine the temporal evolution of iron accumulation and its potential relationship with functional outcomes in mTBI patients.