Magnetite as a Potent Contrast-Enhancing Agent in Magnetic Resonance Imaging to Visualize Blood-Brain Barrier Disruption

  • J. W. M. Bulte
  • M. W. A. de Jonge
  • R. L. Kamman
  • F. Zuiderveen
  • T. H. The
  • L. de Leij
  • K. G. Go
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 57)


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 µM 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 Ti at a DMP concentration of 48 µM Fe, while for T2 only 4 µM/ 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.


Magnetic resonance imaging contrast enhancement dextran magnetite particles blood-brain barrier 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    GoKG, Houthoff HJ, Hartsuiker J, van der Molen-Woldendorp D, Zuiderveen F,Teelken AW (1985) Exudation of plasma protein fractions in vasogenic brainedema. In: Inaba Y, et al (eds) Brain edema. Springer,Berlin Heidelberg New York Tokyo, pp 76–87Google Scholar
  2. 2.
    Houthoff HJ, GoKG, Huitema S (1981) The permeability of cerebral capillary endothelium in coldinjury: comparison of an endogenous and exogenous protein tracer. In:Cervos-Navarro J, Fritschka E (eds) Cerebral microcirculation and metabolism.Raven, New York, pp 331–336Google Scholar
  3. 3.
    Houthoff HJ, Moretz RC, Rennke HG, Wisniewski HM(1984) The role of molecular charge in the extravasation and clearance ofprotein tracers in blood-brain barrier impairment and cerebral edema. In: GoKG, Baethmann A (eds) Recent progress in the study and therapy of brain edema.Plenum, pp 67–79Google Scholar
  4. 4.
    Kamman RL, Go KG,Brouwer W, Berendsen HJC (1988) Nuclear magnetic resonance relaxation inexperimental brain edema: effects of water concentration, proteinconcentration, and temperature. Magn Reson Med 6: 265–274PubMedCrossRefGoogle Scholar
  5. 5.
    Molday RS,MacKenzie D (1982) Immunospecific ferromagnetic iron-dextran reagents for thelabelling and magnetic separation of cells. J Immunol Meth 52: 353–367CrossRefGoogle Scholar
  6. 6.
    Naruse S,Horikawa Y, Tanaka C, Hirakawa K, Nishikawa H, Yoshizaki K (1982) Protonnuclear magnetic resonance studies on brain edema. J Neurosurg 56: 747–752PubMedCrossRefGoogle Scholar
  7. 7.
    NaruseS, Horikawa Y, Tanaka C, Hirakawa K, Nishikawa H, Yoshizaki K (1986)Significance of proton relaxation time measurement in brain edema, cerebralinfarction and brain tumors. Magn Reson Im 4: 293–304CrossRefGoogle Scholar
  8. 8.
    OlssonMBE, Persson BRB, Salford LG, Schröder U (1986) Ferromagnetic particles ascontrast agents in T2 NMR imaging. Magn Reson Med 4: 437–440Google Scholar
  9. 9.
    Renshaw PF, OwenCS, McLaughlin AC, Frey TG, Leigh JS Jr (1986) Ferromagneticcontrast agents: a new approach. Magn Reson Med 3: 217–225PubMedCrossRefGoogle Scholar
  10. 10.
    Renshaw PF, OwenCS, Evans AE, Leigh JS Jr (1986) Immunospecific NMR contrast agents. Magn ResonIm4:351–357Google Scholar
  11. 11.
    RungeVM,Price AC, WehrCJ,etal(1985)Contrast enhanced MRI: evaluation of a canine model of osmotic blood-brainbarrier disruption. Invest Radiol 20: 830–844PubMedCrossRefGoogle Scholar
  12. 12.
    Runge VM, ClantonJA, PriceAC, etal(1985)The use of Gd DTPA as a perfusion agent and marker of blood-brain barrier disruption.Magn Reson Im3:43–55CrossRefGoogle Scholar
  13. 13.
    Saini S, StarkDD, HahnPF, Bousquet J-C,Introcasso J, Wittenberg J, Brady TJ, Ferrucci JT Jr (1987) Ferrite particles:a superparamagnetic MR contrast agent for enhanced detection of livercarcinoma. Radiology 162: 217–222PubMedGoogle Scholar
  14. 14.
    Stark DD, WeisslederR,Elizondo G HahnPF,Saini S, Todd LE, Wittenberg J, Ferrucci JT (1988) Superparamagnetic ironoxide: clinical application as a contrast agent for MR imaging of the liver.Radiology 168: 297–301PubMedGoogle Scholar
  15. 15.
    Tsang Y-M, StarkDD, Chia-Mei Chen M, Weissleder R, Wittenberg J, Ferrucci JT (1988)Hepatic micrometastases in the rat: ferrite-enhanced MR imaging. Radiology 167:21–24PubMedGoogle Scholar
  16. 16.
    Weissleder R, Hahn PF, Stark DD, Rummeny E, Saini S,Witten berg J, Ferrucci JT (1987) MR imagingof splenic metastases: ferrite-enhanced detection in rats. Am J Roentgenol149:723–726Google Scholar
  17. 17.
    Weissleder R, Saini S, StarkDD, Wittenberg J, Ferrucci JT (1988) Dual-contrast MR imaging of liver cancer in rats. Am J Roentgenol 150:561–566Google Scholar
  18. 18.
    Weissleder R, Stark DD,Rummeny EJ, Compton CC, Ferrucci JT (1988) Splenic lymphoma: ferrite-enhancedMR imaging in rats.Radiology 166: 423–430PubMedGoogle Scholar
  19. 19.
    Weissleder R, Hahn PF, Stark DD, Elizondo G, Saini S,Todd LE, Wittenberg J, Ferrucci JT (1988) Superparamagnetic iron oxide: enhanced detection of focal splenic tumors with MR imaging.Radiology 169: 399–403PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • J. W. M. Bulte
    • 1
  • M. W. A. de Jonge
    • 1
  • R. L. Kamman
    • 2
  • F. Zuiderveen
    • 3
  • T. H. The
    • 1
  • L. de Leij
    • 1
  • K. G. Go
    • 3
  1. 1.Department of Clinical ImmunologyUniversity of GroningenThe Netherlands
  2. 2.Department of Magnetic ResonanceUniversity of GroningenThe Netherlands
  3. 3.Department of NeurosurgeryUniversity of GroningenThe Netherlands

Personalised recommendations