Abstract

Amyloid plaques are small (~ 50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer’s disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer’s disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.

Highlights

  • In the large majority of studies on mouse and rat models, the amyloid plaques were quantified histologically in sliced and stained brain tissue

  • We present the absorption based contrast enhanced X-ray micro Computed Tomography (CT) imaging performed on the industrial lab based CT system as an imaging tool for a 3D analysis of Aβ plaques of transgenic rat brains used as a model in Alzheimer disease research

  • The detection of amyloid plaques in rodent brain by Computed Tomography (CT) has been attempted so far by using the mouse brain and the experiments have been performed with synchrotron X-ray sources using variations of phase contrast imaging to visualize the Aβ plaques in a brain

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Summary

Introduction

In the large majority of studies on mouse and rat models, the amyloid plaques were quantified histologically in sliced and stained brain tissue. The main advantage of absorption based contrast enhanced X-ray micro CT imaging is the possibility to obtain precise 3D information about inner structures of the entire brain without sectioning (which might induce artifacts related to brain deformation or missing tissue due to the sectioning). The micro CT imaging of rodent brain has been previously used for the visualization of vascular system of mouse brain filled with radio-opaque silicone rubber M­ icrofil[25,26,27,28,29,30,31], as a tool for localization of cerebral i­schemia[32,33] to test the efficiency of different micro CT contrasting a­ gents[24,25,26,27,28,29,30,31,32,33,34,35,36,37,38], and even for the analysis of specific structures of the b­ rain[39]

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