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Abstract

The strong difference in magnetic susceptibility, χ, between white and grey matter (WM and GM) in Alzheimer’s Disease (AD) can be used to distinguish between AD patients and healthy controls (Acosta-Cabronero et. al, 2013; Van Rooden et., al, 2014). However, the cause behind this difference has not yet been established. Here, we performed biophysical modelling to investigate the contribution from iron-rich β-amyloid plaques to the MRI signal. Field maps were generated using the plaques spatial distribution obtained from β-amyloid stained histologic sections.
Histologic section of post mortem tissue from the frontal cortex of an AD patient stained for β-amyloid was used to determine the spatial distribution of the plaques in microscopic images with a voxel size of 25µm. High resolution MRI was used to estimate the maximal magnetic susceptibility effect of the plaques. Biophysical modelling was performed and maps of the magnetic field caused by the plaques using a voxel size of 25µm were generated. The magnetic field was then averaged for different isotropic voxel sizes (100, 500, 750 and 1000µm).
At small voxel sizes (≤100µm) the magnetic field effect caused by single β-amyloid plaques could be observed (Fig. 1). At the voxel size of 100µm, which is close to the spatial resolution achievable with clinical protocols at ultra high field strenght (≥7T), single plaques effects could not be observed. However, a clear pattern due to the palques can be distinguished at this spatial resolution (Fig. 2).

For greater voxel sizes (500µ and 750µm), only the combined effect of several plaques was detectable. However, even at voxel sizes of 1mm, that can be used on clinical scanners operating at 3T, the magnetic field effect was still noticeable (Fig. 3).
Our modelling results show that iron-rich β-amyloid plaques cannot be directly observed using clinical MRI scanners. However, they may still contribute significantly to the alterations observed in Alzheimer's patients using quantitative MRI. This is of pivotal importance, because they potentially may contribute to the diagnosis of Alzheimer's Disease.