Brain iron deposition in white matter hyperintensities: a 3-T MRI study

Iron accumulation has been implicated in the pathogenesis of demyelinating diseases. Therefore, we hypothesized that abnormal high cerebral iron deposition may be involved in the development of white matter hyperintensities (WMHs). We used R2* relaxometry to assess whether iron levels in different brain regions correlate with the severity of WMHs. This technique has been recently validated in a postmortem study to demonstrate in vivo brain iron accumulation in a quantitative manner. Fifty-two consecutive WMH patients and 30 healthy controls with 3-T magnetic resonance imaging (MRI) were reviewed in this study. We measured WMH volume (as a marker of the severity of WMHs) on MRI, and the transverse relaxation rate R2*, as an estimate of iron content in seven brain regions. We found that R2* in globus pallidus was associated with WMH volume after adjusting for sociodemographic variables (partial correlation coefficient = 0.521, P < 0.001) and in a multivariate analysis adjusted for common vascular risk factors (partial correlation coefficient = 0.572, P = 0.033). Regional R2* in globus pallidus was also significantly higher in WMHs than in controls (P = 0.042). Iron content in globus pallidus, as assessed by R2* relaxometry, is independently linked to the severity of WMHs in our cohort of patients, suggesting that iron deposition in the brain may play a role in the pathogenesis of WMHs. This may provide prognostic information on patients with WMHs and may have implications for therapeutic interventions in WMHs.