Quantitative assessment of iron as a marker of neurodegeneration after traumatic brain injury

Abstract

BACKGROUND: Ferroptosis plays a pivotal role in the pathophysiology of secondary disorders following brain injury. Disturbances in iron homeostasis result in the accumulation of iron and the formation of reactive oxygen species, which may contribute to the development of various neurodegenerative diseases. Magnetic susceptibility mapping is a novel, rapidly evolving quantitative technique with significant potential for assessing iron accumulation in the brain. AIM: The study aimed to determine changes in brain iron concentrations in patients with brain injury using magnetic susceptibility mapping techniques. MATERIALS AND METHODS: The study included 9 patients (14±2 years) with moderate and severe brain injury: three in the acute phase and six in the remote phase, and 4 healthy volunteers (15.3±0.9 years). All study participants underwent magnetic resonance imaging on a Philips Achieva dStream 3T scanner (Philips, the Netherlands). Data for magnetic susceptibility maps were acquired using a 3D FFE multi-echo sequence with flux compensation: FA=20, 6 TE: TE1/dTE=4.422 ms/5.795 ms, TR=59 ms (minimum), matrix size was 400×400×75, voxel size was 0.6×0.6×0.6 mm3. Magnetic susceptibility maps were generated using the SEPIA program. Magnetic field map construction, local magnetic field extraction, and magnetic susceptibility calculation were performed using the Laplacian, LBV, and iLSQR techniques, respectively. Average magnetic susceptibility values were obtained in 16 subcortical gray matter zones using the CIT168 atlas. RESULTS: The preliminary results of the study indicated that the patient group exhibited higher magnetic susceptibility values (p=0.07) in the compact part of the substantia nigra compared to the control group. The values for the patient and control groups were 0.03±0.03 and 0.003±0.018, respectively (Fig. 1). This result suggests a potential difference between the two groups at the level of a statistical trend, which may indicate iron accumulation in this area following brain injury. No changes in the values of magnetic susceptibility were observed in other areas of the subcortical gray matter that were investigated. An increased iron concentration in the compact part of the substantia nigra is also a characteristic of Parkinson’s disease [3]. This is consistent with the fact that brain injury is a risk factor for the development of this neurodegenerative disease. One of the possible causes of iron accumulation is neuronal death and increased permeability of the blood-brain barrier [4]. CONCLUSIONS: An elevated magnetic susceptibility value in the compact part of the substantia nigra in patients with brain injury may indicate the accumulation of iron in this area following injury. A larger sample size will allow for further testing of this hypothesis and the monitoring of changes in iron concentration over time following brain injury.