Abstract
The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness, and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.
Highlights
Sufficiently parallel and homogeneous X-rays to produce biomedically useful phase contrast images at microscopic spatial resolutions
The differential phase contrast (DPC) imaging protocol resulted in high-resolution and high-contrast overviews of the mouse hearts
Several small bright structures were observed in the lower papillary muscles of the ApoE−/− mice, which may be attributed to microcalcifications (Fig. 1I)
Summary
Sufficiently parallel (collimated) and homogeneous (monochromatic) X-rays to produce biomedically useful phase contrast images at microscopic spatial resolutions. A synchrotron essentially is a cyclical particle accelerator that consists of linear stretches linked by bending magnets, at which highly collimated X-ray beams are generated These X-ray sources can be used to produce 3D images at a resolution down to 1 μ m12, and synchrotron phase-contrast CT has for example been applied to characterize human atherosclerotic plaque ex vivo[13]. A more recently developed synchrotron imaging technique is differential phase contrast (DPC) imaging[14], which makes use of two stepped gratings to perform interferometry with a very high soft-tissue contrast[15] Such DPC imaging has for example been applied to detect amyloid plaques in the mouse brain[16] and to improve tumor detection in human breast tissue[17]. The goal of this study was to advance mouse atherosclerosis and cardiovascular imaging by investigating the use of DPC imaging for the visualization of the 3D structure of both microscopic and macroscopic aspects of atherosclerosis in mice for the first time
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