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Virtual histology of animal and human brains with Alzheimer's disease
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International audience. Introduction Synchrotron Radiation X-ray Phase Computed Tomography (SR-PCT) of brain tissue can reveal different image contrast depending on sample preparation. Indeed, we have shown that ethanol dehydration of brain samples reveals myelin as a hyper-intense signal while maintaining optimal detection of packed proteinaceous structures such as amyloid plaques [1]. The present work builds on this versatile “virtual histology” tool to characterize amyloid deposits in brain samples from Alzheimer’s disease (AD) animal models and patients.Methods Mono, bi-, and triple transgenic lines of mouse (PDAPP, APP-PS1, 3xTg [2]) were studied, along with one line of transgenic rats [3]. Human samples of frontal cortex were obtained from 6 sporadic AD cases and 1 familial AD case (Cardiobiotec, CRB-HCL, Lyon, France). All samples were scanned after dehydration in ethanol on beamlines ID19 and ID17 at ESRF. In line propagation imaging was performed at 26keV, voxel size of 6.5μm and 3m free space propagation on ID19 (34 keV, 6.5µm and 11m on ID17). Images were reconstructed using Paganin’s method [4].Results/Discussion All transgenic animal brains (Fig. 1) and human AD (Fig. 2) cases exhibited amyloid signals in the form of bright spots. Myelin-based hyper-intensities enabled a detailed visualisation of white-matter tracts and subsequent structural connectivity. Additionally, vessels appeared hypo-intense in perfused brains from animals (Fig.1) and hyper-intense in human autopsic brains (Fig. 2), probably because of the presence of blood-related iron in non-perfused tissue. Concurrent immunofluorescence analyses of these observations are in progress.Conclusions Whole-brain mouse acquisitions were performed faster (3-10 min) than previously described phase contrast approaches [5]. Human amyloid plaques were evidenced for the first time by SR-PCT. Dehydration-added myelin contrast may be used to highlight unexplored associations between amyloid deposition and myelin alterations.
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