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.