Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues

Abstract

Background Advanced atherosclerotic lesions are commonly characterized by the presence of calcification. Several studies indicate that extensive calcification is associated with plaque stability, yet recent studies suggest that calcification morphology and location may adversely affect the mechanical stability of atherosclerotic plaques. The underlying cause of atherosclerotic calcification and the importance of intra-plaque calcium distribution remains poorly understood. Method The goal of this study was the characterization of calcification morphology based on histological features in 20 human carotid endarterectomy (CEA) specimens. Representative frozen sections (10μm thick) were cut from the common, bulb, internal and external segments of CEA tissues and stained with von Kossa’s reagent for calcium phosphate. The morphology of calcification (calcified patches) and fibrous layer thickness were quantified in 135 histological sections. Results Intra-plaque calcification was distributed heterogeneously (calcification %-area: bulb segment: 14.2±2.1%; internal segment: 12.9±2.8%; common segment: 4.6±1.1%; p=0.001). Calcified patch sizes ranged from <0.1mm2 to >1.0mm2, and were found in 20 CEAs. Calcified patches were most abundant in the bulb and least in the common segment (bulb n=7.30±1.08; internal n=4.81±1.17; common n=2.56±0.56; p=0.0007). Calcified patch circularity decreased with increasing size (<0.1mm2=0.77±0.01, 0.1–1mm2=0.62±0.01, >1.0mm2=0.51±0.02; p=0.0001). A reduced fibrous layer thickness was associated with increased calcium patch size (p<0.0001). Conclusions In advanced carotid atherosclerosis, calcification appears to be a heterogeneous and dynamic atherosclerotic plaque component, as indicated by the simultaneous presence of few large stabilizing calcified patches and numerous small calcific patches. Future studies are needed to elucidate the associations of intra-plaque calcification size and distribution with atherothrombotic events.

Distribution of calcification in carotid endarterectomy tissues: Comparison of micro-computed tomography imaging with histology

“…Spearman correlation between histology sections and corresponding micro-CT image slices for the total calcium area and total AS was 0.80 for CS (p=0.0006), 0.91 for BS (p<0.001), and 0.72 for IES (p=0.0007). The morphological characterization of calcification based on histological features of the CEA tissues has been discussed briefly previously, 11 and a more detailed histological analysis is underway.…”

Calcification patterns in femoral and carotid atheromatous plaques: A comparative morphometric study

“…The majority of studies focusing on calcification are based on calcium score (CS) determination by imaging; few of them use morphometric analysis of mineral content on the histopathological sections of the endarterectomy samples involving one type of artery (21) or two types (18).…”

“…Clinically, two types of plaque calcification have distinct implications in the progression and regression of atherosclerosis: Macrocalcification, which leads to plaque stability, and microcalcification with a pivotal role in plaque rupture and consequent complications (19,20). Recent research has demonstrated that the spatial distribution of mineral mass, calcification size and location are important determinants of the plaque rupture risk (21,22).…”

Incidental paranasal sinusitis on routine brain magnetic resonance scans: association with atherosclerosis

“…Intuitively, an effect favoring CAD would seem the most likely of possible asymmetric associations to Sig IPS. At one level, this speaks to the heterogeneity of atherosclerosis, which is evident morphologically, at the micro‐level and macro‐level . The site‐related risks for developing atherosclerosis and for end‐organ ischemia are modulated by the location and size of affected arteries, the presence of collateral pathways and end‐organ tissue sensitivity, and probably other factors.…”