Ultra-small Super Paramagnetic Iron Oxide predicts higher disease activity in clinically isolated syndrome

Background: Macrophages are important components of inflammatory processes inmultiple sclerosis, closely linked to axonal loss, and can now be observed in-vivo usingUltra-Small super-Paramagnetic Iron Oxide (USPIO). We aimed to determine theprevalence of macrophage infiltration and to assess the predictive value on diseaseactivity and tissue injury after one year in clinical isolated syndrome patients.Methods: Thirty-five patients were imaged using conventional-MRI, magnetizationtransfer ratio (MTR) to assess tissue destructuration, gadolinium (Gd) to probe bloodbrain barrier integrity, and USPIO to study macrophage infiltration.Results: At baseline, patients showed 17 USPIO-positive lesions reflecting infiltrationof macrophages present from the onset. This infiltration was associated with higherlocal tissue destructuration as emphasized by lower MTR values of USPIO-positive/Gdpositivelesions compared to USPIO-negative/Gd-positive and to non-enhanced lesions,at baseline and Month-12, and no difference between USPIO-negative/Gd-positive andnon-enhanced lesions. While at baseline T2-lesion load of patients with USPIOenhancementcompared to patients with Gd-enhancement was not different, it washigher at Month-12. T1-lesion load was also higher at Month-12 in patients withUSPIO-enhancement.Conclusion: Infiltration of activated macrophages evidenced by USPIO enhancement,is present at the onset of MS and is associated with higher local and global progressionof tissue destructuration