Monitoring therapeutic effects in experimental stroke by serial USPIO-enhanced MRI

Objectives This study sought to evaluate whether the therapeutic effects of an anti-inflammatory drug such as minocycline could be monitored by serial ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI in experimental stroke. Methods Mice received a three-dose minocycline treatment ( n = 12) or vehicle ( n = 12) after permanent middle cerebral artery occlusion. USPIOs were administered 5 h post-surgery. MRI was performed before, 24 h and 48 h post-USPIO administration. MRI endpoints were the extent of signal abnormalities on R2 maps (=1/T2) and quantitative R2 changes over time (∆R2). Post-mortem brains were prepared either for immunohistology ( n = 16) or for iron dosage ( n = 8). Results As expected, treatment with minocycline significantly reduced infarct size, blood-brain barrier permeability and F4/80 immunostaining for microglia/macrophages. Areas of R2 maps > 35 ms -1 also appeared significantly decreased in minocycline-treated mice (ANOVA for repeated measures, P = 0.017). There was a fair correlation between these areas and the amount of iron in the brain (R 2 = 0.69, P = 0.010), but no significant difference in ∆R2 was found between the two groups. Conclusions This study showed that the extent of signal abnormalities on R2 maps can be used as a surrogate marker to detect minocycline effects in a murine experimental model of stroke. Key Points • Ultrasmall superparamagnetic particles of iron oxide offer new avenues for MRI research • Treatment of the inflammatory response following ischaemic stroke is currently undergoing evaluation. • Minocycline treatment significantly reduced areas of signal abnormalities on USPIO-enhanced MRI. • These areas correlated with the amount of iron in the brain. • Thus USPIO-enhanced MRI might provide a surrogate marker to monitor treatment