Ex vivo differential phase contrast and magnetic resonance imaging for characterization of human carotid atherosclerotic plaques

Abstract

Non-invasive detection of specific atherosclerotic plaque components related to vulnerability is of high clinical relevance to prevent cerebrovascular events. The feasibility of magnetic resonance imaging (MRI) for characterization of plaque components was already demonstrated. We aimed to evaluate the potential of ex vivo differential phase contrast X-ray tomography (DPC) to accurately characterize human carotid plaque components in comparison to high field multicontrast MRI and histopathology. Two human plaque segments, obtained from carotid endarterectomy, classified according to criteria of the American Heart Association as stable and unstable plaque, were examined by ex vivo DPC tomography and multicontrast MRI (T1-, T2-, and proton density-weighted imaging, magnetization transfer contrast, diffusion-weighted imaging). To identify specific plaque components, the plaques were subsequently sectioned and stained for fibrous and cellular components, smooth muscle cells, hemosiderin, and fibrin. Histological data were then matched with DPC and MR images to define signal criteria for atherosclerotic plaque components. Characteristic structures, such as the lipid and necrotic core covered by a fibrous cap, calcification and hemosiderin deposits were delineated by histology and found with excellent sensitivity, resolution and accuracy in both imaging modalities. DPC tomography was superior to MRI regarding resolution and soft tissue contrast. Ex vivo DPC tomography allowed accurate identification of structures and components of atherosclerotic plaques at different lesion stages, in good correlation with histopathological findings. Methods and ResultsTwo human plaque segments, obtained from carotid endarterectomy, classified according to criteria of the American Heart Association as stable and unstable plaque, were examined by ex vivo DPC tomography and multicontrast MRI (T1-, T2-, and proton density-weighted imaging, magnetization transfer contrast, diffusion-weighted imaging). To identify specific plaque components, the plaques were subsequently sectioned and stained for fibrous and cellular components, smooth muscle cells, hemosiderin, and fibrin. Histological data were then matched with DPC and MR images to define signal criteria for atherosclerotic plaque components. Characteristic structures, such as the lipid and necrotic core covered by a fibrous cap, calcification and hemosiderin deposits were delineated by histology and found with excellent sensitivity, resolution and accuracy in both imaging modalities.DPC tomography was superior to MRI regarding resolution and soft tissue contrast. ConclusionEx vivo DPC tomography allowed accurate identification of structures and components of atherosclerotic plaques at different lesion stages, in good correlation with histopathological findings.3

Sub-micrometer morphology of human atherosclerotic plaque revealed by synchrotron radiation-based μCT—A comparison with histology

“…The largest advancements of our study (comparing to the previous literature [ 10 , 14 , 22 ]) are: 1) the use of more carotid samples from different living patients (not fragments from the same sample), 2) assessed with 3 immunostainings and 2 histological stainings (one of them a pentachrome providing 5 components), 3) depicted with the highest resolution so far due to the combination of a propagation-based phase-contrast method with the synchrotron source. In addition, we performed both low- and high-resolution scans on the samples, using simple embedding, allowing us both a global screening of the sample, as well as zooming in to regions of particular clinical interest without destroying the tissue and in 3D.…”

“…This allows for fast submicron imaging (within minutes), compared to the histological process that typically takes days to weeks. Synchrotron radiation-based and laboratory-based μCT of human atherosclerotic plaques have been conducted by other groups [ 10 , 14 , 22 ]. Still, to the best of our knowledge, this is the first time human carotid plaques have been imaged with phase-contrast μCT with 0.65 μm voxel resolution.…”

Microstructural and mechanical insight into atherosclerotic plaques– an ex vivo DTI study to better assess plaque vulnerability

“…In comparison to ultrasound and computed tomography, magnetic resonance imaging (MRI) is both non-ionising and offers unparalleled soft tissue contrast. A number of studies have used ex vivo MRI to characterise plaque components [28][29][30][31][32][33][34][35] . These studies utilise different combinations of T1-, T2-, proton-density, and diffusion weighted imaging to gain insight into the plaque composition.…”

Quantitative Analysis of Lipid-Rich Necrotic Core in Carotid Atherosclerotic Plaques by In Vivo Magnetic Resonance Imaging and Clinical Outcomes

“…Lipids are the basic components of atherosclerotic plaques [5,6]. Indeed, size of the lipid-rich necrotic core (LRNC) in carotid plaques is believed to be a predictive factor for plaque rupture, and allows distinction between symptomatic and asymptomatic patients [7].…”