title: Use of ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced MRI to demonstrate diffuse inflammation in the normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients: an exploratory study.
abstract: OBJECTIVE
  To explore ultrasmall superparamagnetic particles of iron oxide (USPIO) as a marker for diffuse inflammation in multiple sclerosis (MS) normal-appearing white matter (NAWM), using quantitative MRI. Disease activity in the NAWM of MS patients partly explains why MRI lesion burden correlates only moderately with disability. USPIO have been shown to visualize the cellular component of inflammation in focal MS lesions. In this study, we aimed to explore USPIO as a marker for the more diffuse inflammation in MS NAWM, using quantitative MRI.
  
  
  METHODS
  In this prospective MRI study, 16 MS patients (eight relapsing-remitting MS [RRMS] and eight primary-progressive MS [PPMS] cases) and five healthy control (HC) subjects were included. Using a flip-angle (FA) array, B1-corrected T1 maps were generated before and 24 hours after USPIO (SHU555C) injection. White-matter (WM) T1 histogram and region-of-interest (ROI) characteristics were compared between both time points using Wilcoxon signed-rank test.
  
  
  RESULTS
  Both NAWM ROI and histogram analyses showed T1 shortening after USPIO injection in MS patients (P < 0.01), but not in HCs (P = 0.68).
  
  
  CONCLUSIONS
  This exploratory study suggests that USPIO-enhanced MRI may be a new potential marker for subtle inflammatory activity in MS NAWM. Further studies should focus on relating diffuse inflammation to clinical disease activity and treatment efficacy.
authors.affiliation: Department of Neurology, MS Centre Amsterdam, Amsterdam, the Netherlands. m.vellinga@vumc.nl
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Vellinga
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.forename: Hanneke E
authors.initials: HE
authors.lastname: Hulst
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003287:Contrast Media; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D010087:Oxides; D010316:Particle Size; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide