Amyloid-β plaque deposition measured using propagation-based X-ray phase contrast CT imaging

Abstract

Amyloid beta accumulation into insoluble plaques (Aβp) is known to play a significant role in the pathological process in Alzheimer's disease (AD). The presence of Aβp is also one of the neuropathological hallmarks for the disease. AD final diagnosis is generally acknowledged after the evaluation of Aβp deposition in the brain. Insoluble Aβp accumulation may also concur to cause AD as postulated in the so-called amyloid hypothesis. Therefore, the visualization, evaluation and quantification of Aβp are nowadays the keys for a better understanding of the disease, which may point to a possible cure for AD in the near future. Synchrotron-based X-ray phase contrast (XPC) has been demonstrated as the only imaging method that can retrieve the Aβp signal with high spatial resolution (up to 10 µm), high sensitivity and three-dimensional information at the same time. Although at the moment XPC is suitable for ex vivo samples only, it may develop into an alternative to positron emission tomography and magnetic resonance imaging in Aβp imaging. In this contribution the possibility of using synchrotron-based X-ray phase propagation computed tomography to visualize and measure Aβp on mouse brains is presented. A careful setup optimization for this application leads to a significant improvement of spatial resolution (∼1 µm), data acquisition speed (five times faster), X-ray dose (five times lower) and setup complexity, without a substantial loss in sensitivity when compared with the classic implementation of grating-based X-ray interferometry.

Keywords: Alzheimer's disease; X-ray CT; amyloid plaques; brain imaging; phase contrast.

Figure 1

Sketch of the two setups used. The GI one on the left side of the table (with the water tank and the G1/G2 gratings) and the XPP one that requires a propagation distance between the sample and the detector.

Figure 2

Phase signal reconstructed from (A) GI and (D) XPP/PA of the cortex (CTX) and anterior olfactory nucleus (AON). Horizontal profiles of the plaques marked with the coloured circles normalized to the GI ones (B, E). Zoom of the analyzed plaques (C, F). Sketch showing the image position and orientation according to the anterior (a) and posterior (p) parts of the brain (G). Scale bar 1 mm.

Figure 3

Phase reconstructed slices of the same brain sample obtained at higher resolution using PP, with a pixel size of 1.6 µm (A) and 0.65 µm (B). The image shows part of the cortex (CTX) and anterior olfactory nucleus (AON). The region of interest outlined in A is shown in B. Sketch showing the image position and orientation according to the anterior (a) and posterior (p) parts of the brain (C). Scale bar 500 µm.

Figure 4

Total number of plaques measured with GI (blue) and XPP/PA (red) in ten individual samples.

Figure 5

Projections (coronal A, axial B and sagittal C; orientation scheme shown in D) of the plaque signals (black trace) in a representative three-dimensional brain sample. Three-dimensional rendering with the segmented plaques in red (D). Cortex (CTX), cerebellum (CB) and main olfactory bulb (MOB) regions are indicated along the antero-posterior axis of the brain. Scale bar 2 mm.