title: Fast in vivo imaging of amyloid plaques using μ-MRI Gd-staining combined with ultrasound-induced blood-brain barrier opening.
abstract: Amyloid plaques are one of the major microscopic lesions that characterize Alzheimer's disease. Current approaches to detect amyloid plaques by using magnetic resonance imaging (MRI) contrast agents require invasive procedures to penetrate the blood-brain barrier (BBB) and to deliver the contrast agent into the vicinity of amyloid plaques. Here we have developed a new protocol (US-Gd-staining) that enables the detection of amyloid plaques in the brain of an APP/PS1 transgenic mouse model of amyloidosis after intra-venous injection of a non-targeted, clinically approved MRI contrast agent (Gd-DOTA, Dotarem®) by transiently opening the BBB with unfocused ultrasound (1 MHz) and clinically approved microbubbles (Sonovue®, Bracco). This US-Gd-staining protocol can detect amyloid plaques with a short imaging time (32 min) and high in-plane resolution (29 μm). The sensitivity and resolution obtained is at least equal to that provided by MRI protocols using intra-cerebro-ventricular injection of contrast agents, a reference method used to penetrate the BBB. To our knowledge this is the first study to demonstrate the ability of MR imaging to detect amyloid plaques by using a peripheral intra-venous injection of a clinically approved NMR contrast agent.
authors: URA 2210 CEA/CNRS Laboratoire des maladies neurodégénératives - 18 route du Panorama-BP6 - 92265 Fontenay-aux-Roses Cedex, France. mathieu.santin@icm-institute.org
authors: Mathieu D
authors: MD
authors: Santin
authors: Thomas
authors: T
authors: Debeir
authors: S Lori
authors: SL
authors: Bridal
authors: Thomas
authors: T
authors: Rooney
authors: Marc
authors: M
authors: Dhenain
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000528:radiation effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013010:Sonication / Q000379:methods*; D013194:Staining and Labeling
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate