title: Magnetite as a potent contrast-enhancing agent in magnetic resonance imaging to visualize blood-brain barrier disruption.
abstract: Imaging of blood-brain barrier damage by magnetic resonance was currently studied as to the potential of dextran-magnetite particles (DMP) for contrast enhancement. For that purpose, dextran-T10 (average molecular weight: 10.9 Kilodalton) was complexed with magnetite (Fe3O4) in ammonia. Experimental testing of the agent was made in vivo using Wistar rats with a freezing injury to the brain. DMP was i.v. injected at a dose of 90 microM Fe/kg b.w. followed by 2% Evans blue (0.6 ml). Control animals with trauma were studied without administration of DMP. Histochemical assessments were made to analyze the tissue distribution of DMP in the brain, kidney and liver after fixation in 4% formalin. MR imaging was conducted with 1.5 Tesla field strength with a circular coil 15 min after the freezing insult and administration of DMP. T1- and T2-weighted images were obtained using spin echo sequences among others. Regression analyses indicated a 50% reduction of T1 at a DMP concentration of 48 microM Fe, while for T2 only 4 microM/Fe(DMP) were sufficient for a 50% reduction. DMP was also accumulating in other organs, particularly in the Kupffer cells of the liver. Administration of DMP led to recognition of the freezing lesion as black area in agreement with macroscopical findings obtained by autopsy. In animals with a freezing lesion without administration of DMP, only T2-weighted images demonstrated a somewhat higher intensity attributable to the disruption of the blood-brain barrier. The present findings demonstrate the usefulness of DMP for contrast enhancement of lesions following disruption of the blood-brain barrier.
authors.affiliation: Department of Clinical Immunology, University of Groningen, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Bulte
authors.forename: M W
authors.initials: MW
authors.lastname: de Jonge
authors.forename: R L
authors.initials: RL
authors.lastname: Kamman
authors.forename: F
authors.initials: F
authors.lastname: Zuiderveen
authors.forename: T H
authors.initials: TH
authors.lastname: The
authors.forename: L
authors.initials: L
authors.lastname: de Leij
authors.forename: K G
authors.initials: KG
authors.lastname: Go
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D001930:Brain Injuries / Q000503:physiopathology; D003287:Contrast Media; D003911:Dextrans; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000503:physiopathology; D052203:Ferrosoferric Oxide; D005615:Freezing; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010087:Oxides; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media; D003911:Dextrans; D010087:Oxides; D007501:Iron; D052203:Ferrosoferric Oxide