title: Pluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement.
abstract: Gadolinium-DTPA (Gd-DTPA) is routinely used as a marker for inflammation in MRI to visualize breakdown of the blood-brain barrier (BBB) in multiple sclerosis. Recent data suggest that ultra-small superparamagnetic particles of iron oxide (USPIO) can be used to visualize cellular infiltration, another aspect of inflammation. This project aimed to compare the novel USPIO particle SHU555C to the longitudinal pattern of Gd-DTPA enhancement in multiple sclerosis. Nineteen relapsing-remitting patients were screened monthly using Gd-enhanced MRI. In case of new enhancing lesions, USPIO were injected and 24 h later, MRI was performed and blood was collected to confirm USPIO loading of circulating monocytes. Lesion development was monitored by 3 monthly Gd-DTPA-enhanced scans and a final scan 7-11 months after injection. USPIO-enhancement was observed as hyperintensity on T1-weighted images, whereas no signal changes were observed on T2-weighted-gradient-echo images. In 14 patients with disease activity, 188 USPIO-positive lesions were seen, 144 of which were Gd-negative. By contrast, there were a total of 59 Gd-positive lesions, 15 of which were USPIO negative. Three patterns of USPIO-enhancement were seen: (i) focal enhancement; (ii) ring-like enhancement and (iii) return to isointensity of a previously hypointense lesion. The latter pattern was most frequently observed for lesions that turned out to be transiently hypointense on follow-up scans, and ring-enhancing lesions were less likely to evolve into black holes at follow-up than lesions without ring-like USPIO-enhancement; we speculate this to be associated with repair. In 4% of the USPIO-positive/Gd negative lesions, USPIO-enhancement preceded Gd-enhancement by 1 month. USPIO-enhancement remained visible for up to 3 months in 1.5% of all USPIO-positive lesions. In 29% of the lesions enhancing with both contrast agents, USPIO-enhancement persisted whereas Gd-enhancement had already resolved. In conclusion, the new nano-particle SHU555C provides complementary information to Gd-enhanced MRI, probably related to monocyte infiltration. The use of USPIO-enhanced MRI is likely to lead to more insight in the pluriformity of inflammation in multiple sclerosis.
authors.affiliation: Department of Neurology, University Medical Centre, Amsterdam, The Netherlands. m.vellinga@vumc.nl
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Vellinga
authors.forename: Raoul D
authors.initials: RD
authors.lastname: Oude Engberink
authors.forename: Alexandra
authors.initials: A
authors.lastname: Seewann
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.forename: Christiane
authors.initials: C
authors.lastname: Pering
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D001921:Brain / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D007501:Iron / Q000097:blood; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles; D008297:Male; D009000:Monocytes / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications* / Q000473:pathology; D010087:Oxides / Q000097:blood
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide