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Publication : Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization.

First Author  Tafoya MA Year  2017
Journal  J Magn Reson Imaging Volume  46
Issue  2 Pages  574-588
PubMed ID  27875002 Mgi Jnum  J:350165
Mgi Id  MGI:7661162 Doi  10.1002/jmri.25563
Citation  Tafoya MA, et al. (2017) Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization. J Magn Reson Imaging 46(2):574-588
abstractText  PURPOSE: To optimize magnetic resonance imaging (MRI) of antibody-conjugated superparamagnetic nanoparticles for detecting amyloid-beta plaques and activated microglia in a 3X transgenic mouse model of Alzheimer's disease. MATERIALS AND METHODS: 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). Abeta 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. RESULTS: 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 approximately 24-fold of Abeta plaque density and approximately 4-fold in microglial activation. CONCLUSION: Optimized MRI of antibody-conjugated superparamagnetic nanoparticles served to reveal the 3D distributions of both Abeta plaques and activated microglia and to measure the effects of drug treatments in this 3X Tg model. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:574-588.
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