title: Ultra-small superparamagnetic iron oxide enhancement is associated with higher loss of brain tissue structure in clinically isolated syndrome.
abstract: Macrophages are important components of inflammatory processes in multiple sclerosis, closely linked to axonal loss, and can now be observed in vivo using ultra-small superparamagnetic iron oxide (USPIO). In the present 1-year longitudinal study, we aimed to determine the prevalence and the impact on tissue injury of macrophage infiltration in patients after the first clinical event of multiple sclerosis.
  
  
  
  Thirty-five patients, 32 years mean age, were imaged in a mean of 66 days after their first event using conventional magnetic resonance imaging, gadolinium (Gd) to probe blood-brain barrier integrity, USPIO to study macrophage infiltration and magnetization transfer ratio (MTR) to assess tissue structure integrity. Statistics were performed using two-group repeated-measures ANOVA. Any patient received treatment at baseline.
  
  
  
  At baseline, patients showed 17 USPIO-positive lesions reflecting infiltration of macrophages present from the onset. This infiltration was associated with local higher loss of tissue structure as emphasized by significant lower MTRnorm values (p<0.03) in USPIO(+)/Gd(+) lesions (n=16; MTRnormUSPIO(+)/Gd(+)=0.78 at baseline, MTRnormUSPIO(+)/Gd(+)=0.81 at M12) relative to USPIO(-)/Gd(+) lesions (n=67; MTRnormUSPIO(-)/Gd(+)=0.82 at baseline, MTRnormUSPIO(-)/Gd(+)=0.85 at M12). No interaction in MTR values was observed during the 12 months follow-up (lesion type × time).
  
  
  
  Infiltration of activated macrophages evidenced by USPIO enhancement, is present at the onset of multiple sclerosis and is associated with higher and persistent local loss of tissue structure. Macrophage infiltration affects more tissue structure while tissue recovery during the following year has a similar pattern for USPIO and Gd-enhanced lesions, leading to relative higher persistent local loss of tissue structure in lesions showing USPIO enhancement at baseline.
authors.affiliation: Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Neurologie, Reims, France/Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France adil.maarouf@yahoo.fr.
authors.forename: Adil
authors.initials: A
authors.lastname: Maarouf
authors.affiliation: CHU Rennes, Hôpital Pontchaillou, Service de Radiologie, Rennes, France/INRIA Rennes - VisAGeS Team, Rennes, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Ferré
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Le Troter
authors.affiliation: INRIA Rennes - VisAGeS Team, Rennes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Bannier
authors.affiliation: CHU Toulouse, Hôpital Rangueil, Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berry
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle d'Imagerie Médicale, CEMEREM, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Radiologie, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pierot
authors.affiliation: INRIA Rennes - VisAGeS Team, Rennes, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Barillot
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Centre Hospitalier Universitaire de Reims, Université de Reims Champagne Ardennes, Service de Neurologie, Reims, France/Laboratoire de Psychopathologie et de Neuropsychologie, EA 2027 Université Paris VIII, Saint-Denis Cedex, France.
authors.forename: Ayman
authors.initials: A
authors.lastname: Tourbah
authors.affiliation: CHU Rennes, Hôpital Pontchaillou, Service de Neurologie, Rennes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Edan
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France/APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.affiliation: Aix-Marseille Université, CNRS, CRMBM UMR 7339, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage*; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D003911:Dextrans / Q000008:administration & dosage*; D018450:Disease Progression; D005260:Female; D005602:France; D006801:Humans; D008137:Longitudinal Studies; D008262:Macrophage Activation; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008297:Male; D009410:Nerve Degeneration; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10
keywords: MRI; Multiple sclerosis; USPIO; clinically isolated syndrome; macrophage