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

• DOI: 10.1016/j.neuroimage.2012.07.018
• Publication Date: 2012-07-18T16:49:35Z
• Authors: Axel Montagne; Maxime Gauberti; Richard Macrez; Amandine Jullienne; Aurélien Briens; Jean-Sébastien Ra...; Gaelle Louin; Alain Buisson; Benoit Haelewyn; Fabian Docagne; Gilles Defer; Denis Vivien; Eric Maubert
• Keywords: Male; 0301 basic medicine; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Endothelial Cells; Metal Nanoparticles; Real-Time Polymerase Chain Reaction; Ferric Compounds; Immunohistochemistry; Magnetic Resonance Imaging; Molecular Imaging; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Central Nervous System Diseases; Animals

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.