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Details of two cases of carotid plaque with low-grade calcification (a) and high-grade calcification (b), respectively. Haematoxylin-eosin stain, magnification 10x.
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Background:
Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group showed that Nestin-positive intraplaque neovessels correlated with histological complications. The aim of the present work is to evaluate the relationship between neoangiogenesis, plaque morphology, and clinical instability of the plaque.
Ma...
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Citations
... However, other authors have suggested that the presence of calcium within carotid plaques could represent an independent marker for luminal stenosis and ischemic symptoms [52]. Recent findings indicated that calcified atherosclerotic burden is a marker of plaque instability [53,54]. These discrepancies can be explained by the fact that vessel wall calcification may occur at different stages and pathways of atherogenesis [55][56][57]. ...
The European Society of Cardiovascular Radiology (ESCR) is the European specialist society of cardiac and vascular imaging. This society’s highest priority is the continuous improvement, development, and standardization of education, training, and best medical practice, based on experience and evidence. The present intra-society consensus is based on the existing scientific evidence and on the individual experience of the members of the ESCR writing group on carotid diseases, the members of the ESCR guidelines committee, and the members of the executive committee of the ESCR. The recommendations published herein reflect the evidence-based society opinion of ESCR. We have produced a twin-papers consensus, indicated through the documents as respectively “Part I” and “Part II.” The first document (Part I) begins with a discussion of features, role, indications, and evidence for CT and MR imaging-based diagnosis of carotid artery disease for risk stratification and prediction of stroke (Section I). It then provides an extensive overview and insight into imaging-derived biomarkers and their potential use in risk stratification (Section II). Finally, detailed recommendations about optimized imaging technique and imaging strategies are summarized (Section III). The second part of this consensus paper (Part II) is focused on structured reporting of carotid imaging studies with CT/MR.
Key Points
• CT and MR imaging-based evaluation of carotid artery disease provides essential information for risk stratification and prediction of stroke.
• Imaging-derived biomarkers and their potential use in risk stratification are evolving; their correct interpretation and use in clinical practice must be well-understood.
• A correct imaging strategy and scan protocol will produce the best possible results for disease evaluation.
... [6][7][8]10,17 Recurrent stroke has already been linked with some neuroradiological features in the vulnerable plaque, namely IPH, LPD, ulceration, 10 and calcification. [38][39][40][41] Therefore, plaque characteristics rather than lumen narrowing may have a role in the pathogenesis and in the recurrence of ischemic cerebrovascular events. However, there remains limited characterization of high-risk plaque features in nonobstructive carotid artery plaque. ...
Carotid plaque vulnerability features beyond the degree of stenosis may play a key role in the pathogenesis and recurrence of ischemic cerebrovascular events.
This study sought to compare intraplaque hemorrhage (IPH) as a marker of plaque vulnerability in symptomatic patients with mild (<50%), moderate (50%–69%), and severe (≥70%) carotid artery stenosis.
We included patients who experienced ischemic cerebrovascular events with no other identifiable sources and underwent carotid endarterectomy for mild (n=32), moderate (n=47), and severe (n=58) carotid artery stenosis. The degree of stenosis and imaging hallmarks were assessed by computed tomography angiography or magnetic resonance angiography. Plaque specimens were stained with hematoxylin and eosin and Movat pentachrome staining.
Carotid plaques of patients with mild stenosis had a higher extent of IPH (%) on tissue analysis compared with patients with moderate (mild, 15.7% [interquartile range, 7.8%–26.7%]; moderate, 3.9% [0.0%–9.2%]; P <0.001) and severe carotid artery stenosis (mild, 15.7% [interquartile range, 7.8%–26.7%]; severe, 2.5% [interquartile range, 0.0%–11.2%]; P <0.001). When considering the degree of carotid artery stenosis as a continuous variable, a lower lumen narrowing was associated with higher extent of IPH ( P <0.001; R, −0.329).
Our major finding is the association of IPH with mild carotid artery stenosis based on histological analysis. The current study may suggest that IPH potentially plays a role in the mechanism of stroke in patients with nonobstructive carotid stenosis.
... 9 Similarly, recent findings indicated calcified atherosclerotic burden as a marker of instability. 10,11 These discrepancies could be explained by the fact that vessel wall calcification may occur at different stages and pathways of atherogenesis. [12][13][14] Indeed, it has been recently reported that not only the amount but also the subtype and chemical composition of calcium in atheromatous plaques can affect plaque stability. ...
... Similar finding were subsequently reported by other authors in support of this hypothesis. 10,11 One such study investigated 611 carotid plaques with CT and magnetic resonance imaging and found that larger calcification volume within plaques was associated with higher IPH prevalence and a lower lipid core prevalence in the lesion, supporting that calcification may not be a stabilizing factor. 48 Conversely, other studies have associated the presence of carotid calcification with the presence of plaques stability, 7 as confirmed by some biomechanical and structural analysis. ...
The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.
... Interestingly, in carotid arteries, several papers showed the "protective" effect of calcified plaques (34)(35)(36), also in subjects with severe degree of stenosis. A meta-analysis (37) showed a significant negative relationship between calcified plaque and ipsilateral ischemia (OR, 0.5; 95% CI, 0.4-0.7). ...
Nowadays it is widely accepted that the rupture of the atherosclerotic plaque in coronary and carotid arteries plays a fundamental role in the development of acute myocardial infarctions or cerebrovascular events. In recent years, imaging techniques have explored, with a new level of detail, the atherosclerotic disease generating new evidences that some plaque characteristics are significantly associated to the risk of rupture and subsequent thrombosis or embolization. Moreover, the recent evidence of the anti-atherosclerotic effects determined by lipid-lowering and anti-inflammatory therapies poses a challenge for the choice of therapeutic approaches (best/optimal medical therapy vs. revascularization), maximized by the evidence that coronary and carotid atherosclerosis share common patterns but also differ regarding some important features. In this Review, we discuss the similarities and differences between coronary and carotid artery vulnerable plaque from the imaging point of view and the potential implications for systemic therapies according to the emerging evidence.
... type VII according to the American Heart Association (AHA) [10,11]. A work from our group showed that the histopathological complications defining the type VI "complicated" plaques (i.e., hemorrhage, thrombosis, surface defects) occur in both calcific and non-calcific plaques, making their classification not well-defined [12]. Also a recent study found that the occurrence of carotid radiological calcifications is not correlated with the histopathological complications and with the atherosclerosis risk factors [13]. ...
... At histopathological analysis, the following variables were collected: semi-quantitative assessment of lipid core from 0 to 4+ according to the extension, as previously described [12], grade of inflammatory infiltrate by CD68 IHC (mild, moderate, and severe), number of intraplaque neovessels in "hot spots" (× 40 magnification fields targeting areas where the neoangiogenesis was more represented) by CD34 IHC, presence of histological complications according to AHA, i.e., hemorrhage, surface defects and thrombosis, and the overall AHA classification [11]. The extension of intraplaque calcifications was semi-quantitatively assessed and scored from 0 to 4+ as previously described [12]. ...
... At histopathological analysis, the following variables were collected: semi-quantitative assessment of lipid core from 0 to 4+ according to the extension, as previously described [12], grade of inflammatory infiltrate by CD68 IHC (mild, moderate, and severe), number of intraplaque neovessels in "hot spots" (× 40 magnification fields targeting areas where the neoangiogenesis was more represented) by CD34 IHC, presence of histological complications according to AHA, i.e., hemorrhage, surface defects and thrombosis, and the overall AHA classification [11]. The extension of intraplaque calcifications was semi-quantitatively assessed and scored from 0 to 4+ as previously described [12]. Moreover, we assessed as separate variables the occurrence of calcific cores (CC, defined as heavy calcium deposits superimposed over necrotic lipid plaque cores), with or without microcalcifications (≤ 100 μm), and protruding nodules (PN, defined as concentric nodular calcifications eroding the arterial walls, regardless of the amount of lipids [18]), with or without foci of ectopic bone tissue. ...
Arterial calcification is an actively regulated process, with different morphological manifestations. Micro-RNAs emerged as potential regulators of vascular calcification; they may become novel diagnostic tools and be used for a finest staging of the carotid plaque progression. The present study aimed at characterizing the different miRNA-mRNA axes in carotid plaques according to their histological patterns of calcification. Histopathological analysis was performed on 124 retrospective carotid plaques, with clinical data and preoperatory angio-CT. miRNA analysis was carried out with microfluidic cards. Real-time PCR was performed for selected miRNAs validation and for RUNX-2 and SOX-9 mRNA levels. CD31, CD68, SMA, and SOX-9 were analyzed by immunohistochemistry. miRNA levels on HUVEC cells were analyzed for confirming results under in vitro osteogenic conditions. Histopathological analysis revealed two main calcification subtypes of plaques: calcific cores (CC) and protruding nodules (PN). miRNA array and PCR validation of miR-1275, miR-30a-5p, and miR-30d indicated a significant upregulation of miR-30a-5p and miR-30d in the PN plaques. Likewise, the miRNA targets RUNX-2 and SOX-9 resulted poorly expressed in PN plaques. The inverse correlation between miRNA and RUNX-2 levels was confirmed on osteogenic-differentiated HUVEC. miR-30a-5p and miR-30d directly correlated with calcification extension and thickness at angio-CT imaging. Our study demonstrated the presence of two distinct morphological subtypes of calcification in carotid atheromatous plaques, supported by different miRNA signatures, and by different angio-CT features. These results shed the light on the use of miRNA as novel diagnostic markers, suggestive of plaque evolution.
... On the other hand, calcified carotid plaques are considered a low athero-embolic risk [6]. In our recent study, we observed that plaques with massive calcifications showed the same incidence of histological complications but without influencing clinical symptomatology [7]. ...
Background:
Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the calcified plaques have not yet been described. The primary reason for this lacuna is that decalcification procedures impair protein and nucleic acids contained in the calcified tissue. The aim of our study was to preserve the cellular content of heavily calcified plaques with a new rapid fixation in order to simplify the study of calcifications.
Methods:
Here we applied a fixation method for fresh calcified tissue using the Carnoy's solution followed by an enzymatic tissue digestion with type II collagenase. Immunohistochemistry was performed to verify the preservation of nuclear and cytoplasmic antigens. DNA content and RNA preservation was evaluated respectively with Feulgen staining and RT-PCR. A checklist of steps for successful image analysis was provided. To present the basic features of the F-DNA analysis we used descriptive statistics, skewness and kurtosis. Differences in DNA content were analysed with Kruskal-Wallis and Dunn's post tests. The value of P < 0.05 was considered significant.
Results:
Twenty-four vascular adult tissues, sorted as calcified (14) or uncalcified (10), were processed and 17 fetal tissues were used as controls (9 soft and 8 hard). Cells composing the calcified carotid plaques were positive to Desmin, Vimentin, Osteocalcin or Ki-67; the cellular population included smooth muscle cells, osteoblasts and osteoclasts-like cells and metakaryotic cells. The DNA content of each cell type found in the calcified carotid artery was successfully quantified in 7 selected samples. Notably the protocol revealed that DNA content in osteoblasts in fetal control tissues exhibits about half (3.0 ng) of the normal nuclear DNA content (6.0 ng).
Conclusion:
Together with standard histology, this technique could give additional information on the cellular content of calcified plaques and help clarify the calcification process during atherosclerosis.
... On the other hand, calcified carotid plaques are considered a low athero-embolic risk [6]. In our recent study, we observed that plaques with massive calcifications showed the same incidence of histological complications but without influencing clinical symptomatology [7]. ...
Background Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the calcified plaques have not yet been described. The primary reason for this lacuna is that decalcification procedures impair protein and nucleic acids contained in the calcified tissue. The aim of our study was to preserve the cellular content of heavily calcified plaques with a new rapid fixation in order to simplify the study of calcifications. Methods Here we applied a fixation method for fresh calcified tissue using the Carnoy’s solution followed by an enzymatic tissue digestion with type II collagenase. Immunohistochemistry was performed to verify the preservation of nuclear and cytoplasmic antigens. DNA content and RNA preservation was evaluated respectively with Feulgen staining and RT-PCR. A checklist of steps for successful image analysis was provided. To present the basic features of the F-DNA analysis we used descriptive statistics, skewness and kurtosis. Differences in DNA content were analysed with Kruskal-Wallis and Dunn’s post tests. The value of P < 0.05 was considered significant. Results Twenty-four vascular adult tissues, sorted as calcified (14) or uncalcified (10), were processed and 17 fetal tissues were used as controls (9 soft and 8 hard). Cells composing the calcified carotid plaques were positive to Desmin, Vimentin, Osteocalcin or Ki-67; the cellular population included smooth muscle cells, osteoblasts and osteoclasts-like cells and metakaryotic cells. The DNA content of each cell type found in the calcified carotid artery was successfully quantified in 7 selected samples. Notably the protocol revealed that DNA content in osteoblasts in fetal control tissues exhibits about half (3.0 ng) of the normal nuclear DNA content (6.0 ng). Conclusion Together with standard histology, this technique could give additional information on the cellular content of calcified plaques and help clarify the calcification process during atherosclerosis.
Introduction
The endovascular treatment (EVT) of peripheral artery obstructive disease in TASC-C and D lesions involving the aortic bifurcation is a matter of debate. The aim of this study is to evaluate the technical and clinical success of kissing stenting in this context and to analyze predictors of outcome.
Methods
All patients treated for aorto-iliac TASC-C and D lesions with kissing stenting (from 2012 to 2017) in a 6-year period were retrospectively analyzed. Preoperative anatomical features were evaluated by reviewing Computed Tomography Angiography images in order to identify severe (SIC) vs. not severe iliac calcifications (NSIC). Primary endpoints: Technical Success (TS), Procedural Success (PS), Primary Patency (PP), and Clinical Success (CS). Secondary endpoints: Secondary Patency (SP), Assisted Patency (AP), Survival (S), mid-term procedure-related complications and risk factors that affected TS and mid-term results.
Results
In a 6-year period, 51 patients fulfilled the inclusion criteria. TS was achieved in 49 (96.1%) cases. Thirty-one patients (60.8%) received a dual antiplatelet therapy (DAPT) for at least 1 month after the procedure. 30-day CS was 94.1%. Median follow-up was 45.7 months (IQR: 24.5, 8-86 range). The CS was 92.6% at 3 years, with a PP of 86.8% and a secondary patency of 93.2% at 3 years. Six (13.2%) iliac axis occluded during the first follow-up year. NSIC was statistically and independently associated with a lower PP (73% vs 96%, P= 0.03); DAPT was statistically and independently associated with higher PP compared to single antiplatelet therapy (96% vs 75%, P= 0.03); these results were confirmed by Cox-regression analysis (HR:0.14, 95%,IC:0.01-0.89, P= 0.05 for DAPT analysis; HR:6.8, 95%,IC:1.21-59, P= 0.05 for NSIC analysis).
Conclusions
EVT for TASC C-D is an effective technique. Postoperative stent occlusion is higher in patients with no DAPT and it usually occurs during the first post-operative year. Preoperative NSIC lesions are associated with reduced PP at 3 years of follow-up.
ischaemic stroke. European and US guidelines for prevention of stroke in patients with carotid plaques are based on quantification of the percentage reduction in luminal diameter due to the atherosclerotic process to select the best therapeutic approach. However, better strategies for prevention of stroke are needed because some subtypes of carotid plaques (eg, vulnerable plaques) can predict the occurrence of Stroke represents a massive public health problem. Carotid atherosclerosis plays a fundamental part in the occurence of stroke independent of the degree of stenosis. Advances in imaging techniques have enabled routine characterisation and detection of the features of carotid plaque vulnerability. Intraplaque haemorrhage is accepted by neurologists and radiologists as one of the features of vulnerable plaques, but other characteristics—eg, plaque volume, neovascularisation, and inflammation—are promising as biomarkers of carotid plaque vulnerability. These biomarkers could change current management strategies based merely on the degree of stenosis.
