Vertebrobasilar Junction Angle Over 90°: A Potential Imaging Marker Associated With Vertebrobasilar Atherosclerosis

Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis.Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or <90°.Results: Among 68 patients (mean age = 63.5 ± 9.4 years old; 63.2% were male) with vertebrobasilar atherosclerosis, 33 had a VBJ angle ≥90° and 35 had a VBJ angle <90°. Compared to the vertebrobasilar plaques with VBJ angle <90°, those with VBJ angle ≥90° had a heavier plaque burden (84.35 vs. 70.58%, p < 0.001) and higher prevalence of intraplaque hemorrhage (17.1 vs. 3.3%, p = 0.01). In the regression analyses, the VBJ angle ≥90° was also robustly associated with plaque burden (odds ratio, 1.11; 95% confidential interval, 1.043–1.18; p = 0.001) and intraplaque hemorrhage (odds ratio, 5.776; 95% confidential interval, 1.095–30.46; p = 0.039) of vertebrobasilar atherosclerosis.Conclusion: The VBJ angle over 90° might aggravate the vessel wall condition of the atherosclerotic vertebrobasilar arteries, which might serve as a potential risk factor for vertebrobasilar atherosclerosis.

Carotid Plaques From Symptomatic Patients With Mild Stenosis Is Associated With Intraplaque Hemorrhage

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.

Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging

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.

Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p &gt; 0.05).Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.

Association Between Carotid Artery Perivascular Fat Density and Intraplaque Hemorrhage

Objectives: Perivascular adipose tissue plays a key role in atherosclerosis, but its effects on the composition of carotid atherosclerotic plaques are unknown. This study aimed to investigate the association between inflammatory carotid artery and intraplaque hemorrhage (IPH) in the carotid artery.Methods: This is a single-center retrospective study. Carotid inflammation was assessed by perivascular fat density (PFD) in 72 participants (mean age, 65.1 years; 56 men) who underwent both computed tomography angiography (CTA) and magnetic resonance imaging (MRI) within 2 weeks. The presence of IPH was assessed with MRI. Carotid stenosis, maximum plaque thickness, calcification, and ulceration were evaluated through CTA. The association between PFD and the occurrence of IPH was studied using generalized estimating equations analysis.Results: Of 156 plaques, 72 plaques (46.2%) had IPH. Plaques with IPH showed higher PFD than those without [−41.4 ± 3.9 vs. −55.8 ± 6.5 Hounsfield unit (HU); p &lt; 0.001]. After age, calcification, degree of stenosis, maximum plaque thickness, and ulceration were adjusted for, PFD (OR, 1.96; 95% CI, 1.41–2.73; p &lt; 0.001) was found to be strongly associated with the presence of IPH.Conclusions: A higher PFD is associated with the presence of IPH in the carotid artery. These findings may provide a novel marker to identify carotid IPH and risk stratification.

Gut Microbiome, Functional Food, Atherosclerosis, and Vascular Calcifications—Is There a Missing Link?

The gut microbiome is represented by the genome of all microorganisms (symbiotic, potential pathogens, or pathogens) residing in the intestine. These ecological communities are involved in almost all metabolic diseases and cardiovascular diseases are not excluded. Atherosclerosis, with a continuously increasing incidence in recent years, is the leading cause of coronary heart disease and stroke by plaque rupture and intraplaque hemorrhage. Vascular calcification, a process very much alike with osteogenesis, is considered to be a marker of advanced atherosclerosis. New evidence, suggesting the role of dietary intake influence on the diversity of the gut microbiome in the development of vascular calcifications, is highly debated. Gut microbiota can metabolize choline, phosphatidylcholine, and L-carnitine and produce vasculotoxic metabolites, such as trimethylamine-N-oxide (TMAO), a proatherogenic metabolite. This review article aims to discuss the latest research about how probiotics and the correction of diet is impacting the gut microbiota and its metabolites in the atherosclerotic process and vascular calcification. Further studies could create the premises for interventions in the microbiome as future primary tools in the prevention of atherosclerotic plaque and vascular calcifications.

Ultrasound Elastography: another piece in the puzzle of carotid plaque vulnerability?

Recent literature has shown that various carotid plaque features, other than stenosis, contribute to plaque vulnerability. Features such as surface morphology and plaque composition with distinct components (e.g. intraplaque hemorrhage, lipid core) have been associated with the increased risk of future cerebrovascular events. Ultrasonography constitutes the first line modality for the assessment of carotid disease and has traditionally been used to grade stenosis with high accuracy. Recenttechnological advances such as contrast-enhanced ultrasound and elastography increased the diagnostic yield of ultrasound in assessing the morphology of carotid plaques. The purpose of this review is to present the available literature on ultrasound elastography of the atherosclerotic carotid. Strain and shear wave elastography allow for the characterization of plaque components, thus indicating its nature and importantly, the plaque’s vulnerability. Shear wave elastography indices appear morerobust than Strain indices. Overall, elastography is a feasible method to distinguish vulnerable carotid plaques. There is, however, a need for larger and longer prospective controlled clinical studies in order to validate elastography as an imaging modality used for the detection of unstable carotid plaques.

Intraplaque high-intensity signal on time-of-flight magnetic resonance angiography and restenosis after carotid artery stenting

OBJECTIVE To test the hypothesis that intraplaque hemorrhage is a predictor of restenosis after carotid artery stenting (CAS), the association between intraplaque high-intensity signal (HIS) on time-of-flight MR angiography (TOF-MRA), as a marker of intraplaque hemorrhage, and restenosis after CAS was assessed in the present observational study. METHODS Consecutive patients who underwent initial CAS for atherosclerotic stenosis in the cervical internal carotid artery in the authors’ department were enrolled. Of these, patients without preprocedural cervical TOF-MRA were excluded. Outcome measures were ≥ 50% restenosis, defined as a peak systolic velocity of > 1.3 m/sec; or occlusion and ≥ 70% restenosis, defined as a peak systolic velocity of > 2.1 m/sec; or occlusion on carotid duplex ultrasound. RESULTS Of 230 consecutive patients who underwent initial CAS, 22 without preprocedural cervical TOF-MRA were excluded. Of the remaining 208 patients (mean age 73 years; 33 women), 46 had intraplaque HIS. Ultrasound follow-up was not performed in 4 patients. The median follow-up duration was 3.2 years (interquartile range 1.7–5.1 years). During the follow-up period, 102 patients had ≥ 50% restenosis and 36 had ≥ 70% restenosis. Intraplaque HIS was significantly associated with increased risk of ≥ 50% restenosis (adjusted hazard ratio 2.18; 95% CI 1.28–3.68) and ≥ 70% restenosis (adjusted hazard ratio 3.12; 95% CI 1.32–7.52). CONCLUSIONS Intraplaque HIS on TOF-MRA was associated with increased risk of restenosis after CAS. The present results indicate that intraplaque hemorrhage is a predictor of restenosis after CAS.