Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer’s Disease (APP/PS1)

Abstract. Murine models of Alzheimer’s disease (AD) provide means to detect and follow biomarker changes similar to those observed in humans. Non-invasive biomarkers, such as those provided by magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are highly desirable, however, systematic studies of in vivo MRI/MRS methods to characterize the cerebral morphology and metabolic pattern of these mice remain scarce. We investigated sixteen consecutive slices from the brain of wild-type and APP/PS1 mice, obtaining a collection of T2-weighted, diffusion weighted and magnetization transfer weighted images as well as 1H PRESS spectra from the cortical and subcortical areas. Compared to controls, APP/PS1 mice show significant regional hyperintensities in T2-weighted images of the cerebral cortex, significant ventricular enlargement, and decreased 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 implemented considering all parameters investigated, and revealed the most characteristic changes and allowed for the correct classification of control and APP/PS1 mice. In summary, the present results provide a useful frame to evaluate optimal MRI/MRS biomarkers for the characterization of AD models, potentially applicable in drug discovery processes, because of their non-invasive an