Assessment of Blood Brain Barrier Leakage with Gadolinium-Enhanced MRI

  • Min-Chi Ku
  • Sonia Waiczies
  • Thoralf Niendorf
  • Andreas PohlmannEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1718)


The integrity of the blood–brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T1-weighted images taken prior to and after CA injection. This MR method is useful for investigating BBB permeability in in vivo mouse models and can be easily applied in a number of experimental disease conditions including neuroinflammation disorders, or to assess (un)wanted drug effects.

Key words

Magnetic resonance imaging (MRI) Mouse Blood brain barrier (BBB) contrast agent (CA) 



The authors wish to thank Till Hülnhagen, Henning Reimann, and Joao Periquito for the development of all custom made analysis tools with MATLAB program.


  1. 1.
    Cecchelli R, Berezowski V, Lundquist S, Culot M, Renftel M, Dehouck MP, Fenart L (2007) Modelling of the blood-brain barrier in drug discovery and development. Nat Rev Drug Discov 6(8):650–661. CrossRefPubMedGoogle Scholar
  2. 2.
    Fernandez-Lopez D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, Wendland MF, Vexler ZS (2012) Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat. J Neurosci 32(28):9588–9600. CrossRefPubMedGoogle Scholar
  3. 3.
    Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, Larsson HB (2015) Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis. Brain 138(Pt 9):2571–2583. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Shlosberg D, Benifla M, Kaufer D, Friedman A (2010) Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol 6(7):393–403. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Marques F, Sousa JC, Sousa N, Palha JA (2013) Blood-brain-barriers in aging and in Alzheimer's disease. Mol Neurodegener 8:38. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Abdul Muneer PM, Alikunju S, Szlachetka AM, Murrin LC, Haorah J (2011) Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction. Mol Neurodegener 6:23. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Patel JP, Frey BN (2015) Disruption in the blood-brain barrier: the missing link between brain and body inflammation in bipolar disorder? Neural Plast 2015:708306. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Banks WA (2012) Brain meets body: the blood-brain barrier as an endocrine interface. Endocrinology 153(9):4111–4119. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Banks WA (2016) From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov 15(4):275–292. CrossRefPubMedGoogle Scholar
  10. 10.
    Blockx I, Einstein S, Guns PJ, Van Audekerke J, Guglielmetti C, Zago W, Roose D, Verhoye M, Van der Linden A, Bard F (2016) Monitoring blood-brain barrier integrity following amyloid-beta immunotherapy using gadolinium-enhanced MRI in a PDAPP mouse model. J Alzheimers Dis 54(2):723–735. CrossRefPubMedGoogle Scholar
  11. 11.
    Chacko AM, Li C, Pryma DA, Brem S, Coukos G, Muzykantov V (2013) Targeted delivery of antibody-based therapeutic and imaging agents to CNS tumors: crossing the blood-brain barrier divide. Expert Opin Drug Deliv 10(7):907–926. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Absinta M, Sati P, Reich DS (2016) Advanced MRI and staging of multiple sclerosis lesions. Nat Rev Neurol 12(6):358–368. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lin Y, Pan Y, Wang M, Huang X, Yin Y, Wang Y, Jia F, Xiong W, Zhang N, Jiang JY (2012) Blood-brain barrier permeability is positively correlated with cerebral microvascular perfusion in the early fluid percussion-injured brain of the rat. Lab Invest 92(11):1623–1634. CrossRefPubMedGoogle Scholar
  14. 14.
    Heye AK, Culling RD, Valdes Hernandez Mdel C, Thrippleton MJ, Wardlaw JM (2014) Assessment of blood-brain barrier disruption using dynamic contrast-enhanced MRI. A systematic review. NeuroImage Clin 6:262–274. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Barnes SR, Ng TS, Montagne A, Law M, Zlokovic BV, Jacobs RE (2016) Optimal acquisition and modeling parameters for accurate assessment of low Ktrans blood-brain barrier permeability using dynamic contrast-enhanced MRI. Magn Reson Med 75(5):1967–1977. CrossRefPubMedGoogle Scholar
  16. 16.
    Larsson HB, Courivaud F, Rostrup E, Hansen AE (2009) Measurement of brain perfusion, blood volume, and blood-brain barrier permeability, using dynamic contrast-enhanced T(1)-weighted MRI at 3 tesla. Magn Reson Med 62(5):1270–1281. CrossRefPubMedGoogle Scholar
  17. 17.
    Feng Y, Jeong EK, Mohs AM, Emerson L, ZR L (2008) Characterization of tumor angiogenesis with dynamic contrast-enhanced MRI and biodegradable macromolecular contrast agents in mice. Magn Reson Med 60(6):1347–1352. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Niendorf T, Pohlmann A, Reimann HM, Waiczies H, Peper E, Huelnhagen T, Seeliger E, Schreiber A, Kettritz R, Strobel K, Ku MC, Waiczies S (2015) Advancing cardiovascular, neurovascular, and renal magnetic resonance imaging in small rodents using cryogenic radiofrequency coil technology. Front Pharmacol 6:255. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wagenhaus B, Pohlmann A, Dieringer MA, Els A, Waiczies H, Waiczies S, Schulz-Menger J, Niendorf T (2012) Functional and morphological cardiac magnetic resonance imaging of mice using a cryogenic quadrature radiofrequency coil. PLoS One 7(8):e42383. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Min-Chi Ku
    • 1
  • Sonia Waiczies
    • 1
  • Thoralf Niendorf
    • 1
    • 2
  • Andreas Pohlmann
    • 1
    Email author
  1. 1.Berlin Ultrahigh Field Facility (B.U.F.F.)Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)BerlinGermany
  2. 2.DZHK (German Centre for Cardiovascular Research)Partner Site BerlinGermany

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