Ultra-sensitive molecular MRI of cerebrovascular cell activation enables early detection of chronic central nervous system disorders.
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.
INSERM, INSERM U919 Serine Protease and Pathophysiology of the Neurovascular Unit, University Caen Basse-Normandie, GIP Cyceron, Bd Becquerel, BP5229, 14074 Caen, France.
Axel
A
Montagne
Maxime
M
Gauberti
Richard
R
Macrez
Amandine
A
Jullienne
Aurélien
A
Briens
Jean-Sébastien
JS
Raynaud
Gaelle
G
Louin
Alain
A
Buisson
Benoit
B
Haelewyn
Fabian
F
Docagne
Gilles
G
Defer
Denis
D
Vivien
Eric
E
Maubert
D000818:Animals; D015153:Blotting, Western; D002493:Central Nervous System Diseases / Q000175:diagnosis*; D042783:Endothelial Cells / Q000378:metabolism*; D005290:Ferric Compounds; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005290:Ferric Compounds; C000499:ferric oxide