Magnetization transfer contrast profiling of APP/PS1 mouse brain indicates the presence of amyloid plaques

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Event Abstract Back to Event Magnetization transfer contrast profiling of APP/PS1 mouse brain indicates the presence of amyloid plaques Christian Bigot1*, Greetje Vanhoutte1, Marleen Verhoye1, Sandra Pereson2, Bob Asselbergh2, Christine Van Broeckhoven2 and Annemie Van Der Linden1 1 University of Antwerp, Biomedical sciences, Belgium 2 University of Antwerp, molecular genetics, Belgium 1. Purpose The presence of amyloid plaques in the brain is one of the pathological hallmarks of Alzheimer’s disease (AD). We introduce magnetic transfer contrast (MTC) imaging as a new technique to non-invasively detect the presence of amyloid plaques. In brain tissue, macromolecular protons, e.g. from amyloid plaques, are characterized by a broader absorption line shape than liquid proton, which makes them sensitive to off-resonance irradiation. A pre-saturation pulse at an appropriate offset frequency followed by excitation at the center frequency will induce an exchange process in which the spin state of liquid protons is influenced by the spin state of macromolecular protons [1, 2]. We used APP/PS1 mice as a model for AD which are characterized by an early deposition of amyloid plaques without the occurrence of tau pathology and neurodegeneration [3]. Since amyloid plaques consist of a thick network of macromolecules, we hypothesized that amyloid plaques can be saturated with a certain frequency, resulting in local higher MTR-values. Our results support our hypothesis. 2. Material and Methods MTC was conducted on a 9,4T MR system (Bruker Biospec, Ettlingen) on 18 months old APP(swe)-PS1(L166p) mice of either sex and age-matched control littermates (nTg= 10; nWT= 11). Images were acquired with a pre-saturation pulse (pulse strength = 12μT, number of pulses = 36, pulse length = 40ms, saturation time = 1440ms) at different offset frequencies ranging from 1000 to 25000Hz, with a spin-echo sequence (TE/TR = 5.36/1767 ms, matrix size = 256*256, field of view = 2.51*2.51 cm, slice thickness = 1mm, NA = 1). MTR's were obtained from acquisitions with and without off-resonance irradiation using Amira (Mercury Computer systems, San Diego). Within Amira, regions of interest (cortex and hippocampus) were delineated and their mean MTR values were extracted for the different applied frequency offsets. Differences of parameters between genotypes were computed by means of a non-parametric Kruskal Wallis test. To validate our study, mice (ntg=5, Wt=5) were sacrificed for histology and these data will soon be available. 3. Results We observed significantly higher MTR- values (p-value < 0.05) in the cortex, hippocampus and thalamus of APP/PS1 mice as compared to control. In the cortex, significant differences between genotypes were found at 5000, 7500, 10000, and 20000Hz (fig.1A). MTR values of 10000Hz were also significant higher in the hippocampus of APP/PS1 mice (fig.1B). Offset frequency 22500Hz rendered significant higher MTR-values in both hippocampus and thalamus of APP/PS1 mice (fig.1B and 1C). Figure 2 demonstrates MTR maps and corresponding MTR values of an individual APP/PS1 and WT mouse at offset frequencies 10000 and 22500Hz. 4. Conclusion From our results we conclude that MTC is able to differ between APP/PS1 and control mice. Since amyloidosis is the principal event in the APP/PS1 AD mouse model, we assume that the differences in MTR-values between APP/PS1 and control are due to the presence of amyloid plaques. Our previous observations have shown that amyloid load is clearly higher in APP/PS1 mice as compared to control (fig. 3). However, since MTC saturates many macromolecules, we draw this conclusion with caution. Further upcoming histological data of each subject might give a closer correlation between higher local MTR values and the presence of amyloid plaques. Figure 1 Figure 2 Figure 3 Acknowledgements This work was in part supported by EC-FP7 project NAD.