Using quantitative MRI to study brain responses to immune challenge with interferon-α

Abstract

Inflammatory processes in the Central Nervous System (CNS) have been proposed to mediate the association between peripheral inflammation and the development of psychiatric disorders, but we currently lack sensitive measures of CNS inflammation for human studies in vivo. Here we used quantitative MRI (qMRI) to explore the in vivo central response to a peripheral immune challenge in healthy humans, and we assessed whether changes in quantitative relaxometry MRI parameters were associated with changes in peripheral inflammation.Quantitative relaxation times (T1 & T2) and Proton Density (PD) were measured in n ​= ​6 healthy males (mean age ​= ​30.5 ​± ​6.8 years) in two MRI assessments collected before and 24 ​hours after a subcutaneous injection of the proinflammatory cytokine and immune activator, interferon-alpha (IFN-α). Serum levels of immune markers and markers of blood-brain barrier integrity (S100B) were also measured before and after the injection.Region of interest and histogram-based analyses (optimized for the small sample size) showed a statistically significant increase of both T1 (t(5) ​= ​3.78, p ​= 0.013) and PD (t(5) ​= ​2.91, p ​= ​0.033) parameters in the bilateral hippocampus after IFN-α administration. T1 peak values in bilateral hippocampus were positively correlated with serum Tumour Necrosis Factor-alpha levels at 24 ​h after the injection, when this cytokine peaked (Spearman's rho ​= ​0.67, p ​= ​0.018) and negatively correlated with S100B levels (Spearman's rho ​= ​−0.826, p ​= ​0.001).Our data suggest that peripheral administration of IFN-α produces acute changes in brain qMRI which might indicate a brain immune response. This is supported by the association of such changes with low-grade peripheral inflammation.