title: Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization.
abstract: To optimize magnetic resonance imaging (MRI) of antibody-conjugated superparamagnetic nanoparticles for detecting amyloid-β plaques and activated microglia in a 3X transgenic mouse model of Alzheimer's disease.
  
  
  
  Ten 3X Tg mice were fed either chow or chow containing 100 ppm resveratrol. Four brains, selected from animals injected with either anti-amyloid targeted superparamagnetic iron oxide nanoparticles, or anti-Iba-1-conjugated FePt-nanoparticles, were excised, fixed with formalin, and placed in Fomblin for ex vivo MRI (11.7T) using multislice-multiecho, multiple gradient echo, rapid acquisition with relaxation enhancement, and susceptibility-weighted imaging (SWI). Aβ plaques and areas of neuroinflammation appeared as hypointense regions whose number, location, and Z-score were measured as a function of sequence type and echo time.
  
  
  
  The MR contrast was due to the shortening of the transverse relaxation time of the plaque-adjacent tissue water. A theoretical analysis of this effect showed that the echo time was the primary determinant of plaque contrast and was used to optimize Z-scores. The Z-scores of the detected lesions varied from 21 to 34 as the echo times varied from 4 to 25 msec, with SWI providing the highest Z-score and number of detected lesions. Computation of the entire plaque and activated microglial distributions in 3D showed that resveratrol treatment led to a reduction of ∼24-fold of Aβ plaque density and ∼4-fold in microglial activation.
  
  
  
  Optimized MRI of antibody-conjugated superparamagnetic nanoparticles served to reveal the 3D distributions of both Aβ plaques and activated microglia and to measure the effects of drug treatments in this 3X Tg model.
  
  
  
  1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:574-588.
authors.affiliation: UNM BRaIN Center, Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Tafoya
authors.affiliation: Bruker BioSpin Corp, Billerica, Massachusetts, USA.
authors.forename: Saaussan
authors.initials: S
authors.lastname: Madi
authors.affiliation: UNM BRaIN Center, Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Laurel O
authors.initials: LO
authors.lastname: Sillerud
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry; D058227:Amyloidogenic Proteins / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000737:chemistry; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D053768:Metal Nanoparticles; D051379:Mice; D008822:Mice, Transgenic; D008823:Micelles; D017628:Microglia; D009154:Mutation; D058225:Plaque, Amyloid; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D058227:Amyloidogenic Proteins; D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D008823:Micelles; D013267:Stilbenes; C000499:ferric oxide; D000077185:Resveratrol
keywords: FePt nanoparticles; SPIONs; Z-scores; resveratrol