Systematic evaluation of magnetic resonance imaging and spectroscopy techniques for imaging a transgenic model of Alzheimer´s disease (AβPP/PS1)

Abstract

Murine models of Alzheimer’s disease (AD) provide means to detect and follow biomarker changes similar to thoseobserved in humans. Non-invasive biomarkers, such as those provided by magnetic resonance imaging (MRI) and spectroscopy(MRS) methods are highly desirable, however, systematic studies ofin vivoMRI/MRS methods to characterize the cerebralmorphology and metabolic pattern of these mice remain scarce. We investigated sixteen consecutive slices from the brain ofwild-type and A PP/PS1 mice, obtaining a collection of T2-weighted, diffusion weighted and magnetization transfer weightedimages as well as1H PRESS spectra from the cortical and subcortical areas. Compared to controls, A PP/PS1 mice showsignificant regional hyperintensities in T2-weighted images of the cerebral cortex, significant ventricular enlargement, anddecreased hippocampal area and fractional magnetization transfer. MRS demonstrated an increase in the ratio of choline (Cho)to creatine (Cr) in the cortical and subcortical areas of the transgenic animals. A logistic regression classifier was implementedconsidering all parameters investigated, and revealed the most characteristic changes and allowed for the correct classification ofcontrol and A PP/PS1 mice. In summary, the present results provide a useful frame to evaluate optimal MRI/MRS biomarkersfor the characterization of AD models, potentially applicable in drug discovery processes, because of their non-invasive andrepeatable nature in longitudinal studies.