Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders

Axel Montagne, Maxime Gauberti, Richard Macrez, Amandine Jullienne, Aurélien Briens, Jean-Sébastien Raynaud, Gaelle Louin, Alain Buisson, Benoit Haelewyn, Fabian Docagne, Gilles Defer, Denis Vivien, Eric Maubert

Research output: Contribution to journalArticlepeer-review

Abstract

Since endothelial cells can be targeted by large contrast-carrying particles, molecular imaging of cerebrovascular cell activation is highly promising to evaluate the underlying inflammation of the central nervous system (CNS). In this study, we aimed to demonstrate that molecular magnetic resonance imaging (MRI) of cerebrovascular cell activation can reveal CNS disorders in the absence of visible lesions and symptoms. To this aim, we optimized contrast carrying particles targeting vascular cell adhesion molecule-1 and MRI protocols through both in vitro and in vivo experiments. Although, pre-contrast MRI images failed to reveal the ongoing pathology, contrast-enhanced MRI revealed hypoperfusion-triggered CNS injury in vascular dementia, unmasked amyloid-induced cerebrovascular activation in Alzheimer's disease and allowed monitoring of disease activity during experimental autoimmune encephalomyelitis. Moreover, contrast-enhanced MRI revealed the cerebrovascular cell activation associated with known risk factors of CNS disorders such as peripheral inflammation, ethanol consumption, hyperglycemia and aging. By providing a dramatically higher sensitivity than previously reported methods and molecular contrast agents, the technology described in the present study opens new avenues of investigation in the field of neuroinflammation.

Original languageEnglish
Pages (from-to)760-70
Number of pages11
JournalNeuroImage
Volume63
Issue number2
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • Animals
  • Blotting, Western
  • Central Nervous System Diseases/diagnosis
  • Endothelial Cells/metabolism
  • Ferric Compounds
  • Immunohistochemistry
  • Magnetic Resonance Imaging/methods
  • Male
  • Metal Nanoparticles
  • Mice
  • Mice, Inbred C57BL
  • Molecular Imaging/methods
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

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