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

PLoS One. 2022 Apr 26;17(4):e0265598. doi: 10.1371/journal.pone.0265598. eCollection 2022.

Abstract

Histology is a long standing and well-established gold standard for pathological characterizations. In recent years however, synchrotron radiation-based micro-computed tomography (SRμCT) has become a tool for extending the imaging of two-dimensional thin sections into three-dimensional imaging of tissue blocks, enabling so-called virtual histology with arbitrary clipping planes, volumetric rendering and automatic segmentation. In this study, we present a thorough characterization of human carotid plaques after endarterectomy of patients with stroke or transient ischemic attack (TIA), investigating several different pathologic structures using both SRμCT and histology. Phase-contrast SRμCT was performed with two different magnifications (voxel sizes 6.5 μm and 0.65 μm, respectively), and histology was performed with multiple different stainings (Alpha-actin, Glycophorin A, von Kossa, Movat, CD68). The 0.65 μm high-resolution SRμCT was performed on selected areas with plaque typical relevant morphology, identified on the 6.5 μm low-resolution SRμCT. The tomography datasets were reconstructed with additional 3D volume rendering and compared to histology. In total, nine different regions with typical pathologic structures were identified and imaged with high-resolution SRμCT. The results show many characteristics typical for advanced atherosclerotic plaques, clinically relevant, namely ruptures with thrombosis, neo-vascularization, inflammatory infiltrates in shoulder regions, lipid rich necrotic cores (LRNC), thin fibrous cap, calcifications, lumen irregularities, and changes in vessel wall structures such as the internal elastic membrane. This method's non-destructive nature renders details of micro-structures with an excellent visual likeness to histology, with the additional strength of multiplanar and 3D visualization and the possibility of multiple re-scans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology
  • Humans
  • Ischemic Attack, Transient* / pathology
  • Plaque, Atherosclerotic* / diagnostic imaging
  • Plaque, Atherosclerotic* / pathology
  • Synchrotrons
  • X-Ray Microtomography / methods

Grants and funding

JW: Crafoordska Stiftelsen grant 20180610 JW: Region Skåne grants I-ALF 47447 and YF-ALF 43435 IG: Swedish research council grant 2019-01260 IG: Hjärt-Lungfonden grant 20200403 IG: Skånes Universitetssjukhus grant 2020-O000028 IG: Swedish Foundation for Strategic Research, grant IRC15-0067 MB: Swedish research council grants 2014-06054 and 2018-06197 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.