Matilde Inglese
Very little is known about the mechanisms leading to brain damage and development of disabling physical, cognitive, and emotional symptoms after mild traumatic brain injury (MTBI). MTBI accounts for 90% of the new cases of head trauma diagnosed annually in the United States, with an annual incidence rate as high as 128/100,000.
We hypothesized that trauma-induced molecular mechanisms may trigger iron accumulation that, in turn, may contribute to permanent tissue injury underpinning cognitive and behavioral deficits in patients with MTBI. It has been shown that although iron is essential for many metabolic functions, abnormal tissue deposition can be injurious to the CNS by inducing oxidative stress that facilitates neuronal death and neurodegeneration. We tested our hypothesis using magnetic field correlation (MFC), a novel MRI technique that is sensitive to the presence of iron deposits. Unlike other conventional MRI methods for measuring iron accumulation, MFC, developed by our collaborator Dr. Jensen, has a more direct relationship to the magnetic field inhomogeneities created by spatial variations in magnetic susceptibility, such as those generated by iron-rich cells.
Our findings of increased MFC in the thalami, globus pallidus, and frontal white matter of patients with MTBI have several implications. First of all, our findings suggest that tissue iron accumulation may play a role in the pathophysiologic cascade of events following the traumatic insult; second, our study corroborates the evidence that the shear stress forces associated with the traumatic event induce not only white matter injury but also subcortical gray matter injury; finally, these results open new avenues for treatment and biomarker developments. Longitudinal and larger studies are ongoing, to better elucidate the dynamics of tissue iron changes since the very early stage of the traumatic event and to investigate the timing and role of iron accumulation in addition to its clinical impact.