Evolving Concepts in Plaque Characterization

Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to rupture and thus to induce an ischemic event is directly related to its composition. Consequently, characterization of the plaque composition and its proneness to rupture are of crucial importance for risk assessment and treatment strategies. The carotid is an excellent artery to be imaged with ultrasound because of its superficial position. In this review, ultrasound-based methods for characterizing the mechanical properties of the carotid wall and atherosclerotic plaque are discussed. Using conventional echography, the intima media thickness (IMT) can be quantified. There is a wealth of studies describing the relation between IMT and the risk for myocardial infarction and stroke. Also the carotid distensibility can be quantified with ultrasound, providing a surrogate marker for the cross-sectional mechanical properties. Although all these parameters are associated with CVD, they do not easily translate to individual patient risk. Another technique is pulse wave velocity (PWV) assessment, which measures the propagation of the pressure pulse over the arterial bed. PWV has proven to be a marker for global arterial stiffness. Recently, an ultrasound-based method to estimate the local PWV has been introduced, but the clinical effectiveness still needs to be established. Other techniques focus on characterization of plaques. With ultrasound elastography, the strain in the plaque due to the pulsatile pressure can be quantified. This technique was initially developed using intravascular catheters to image coronaries, but recently noninvasive methods were successfully developed. A high correlation between the measured strain and the risk for rupture was established. Acoustic radiation force impulse (ARFI) imaging also provides characterization of local plaque components based on mechanical properties. However, both elastography and ARFI provide an indirect measure of the elastic modulus of tissue. With shear wave imaging, the elastic modulus can be quantified, although the carotid artery is one of the most challenging tissues for this technique due to its size and geometry. Prospective studies still have to establish the predictive value of these techniques for the individual patient. Validation of ultrasound-based mechanical characterization of arteries and plaques remains challenging. Magnetic resonance imaging is often used as the "gold" standard for plaque characterization, but its limited resolution renders only global characterization of the plaque. CT provides information on the vascular tree, the degree of stenosis, and the presence of calcified plaque, while soft plaque characterization remains limited. Histology still is the gold standard, but is available only if tissue is excised. In conclusion, elastographic ultrasound techniques are well suited to characterize the different stages of vascular disease.

Atherothrombosis is a systemic disease of the vessel wall that causes distinct clinical manifestations, depending on the affected circulatory bed and the characteristics of the individual lesions.1 These lesions may be quite heterogeneous.1 Thus, the clinical manifestations of atherothrombosis of the coronary arteries, of the arteries supplying the central nervous system, of the aorta, and of the peripheral circulation can be significantly different. Disruption-prone plaques in the coronary arteries, the so-called “vulnerable plaques,” tend to have a thin fibrous cap (cap thickness ≈65 to 150 μm) and a large lipid core (American Heart Association [AHA] plaque type IV-Va). Acute coronary syndromes often result from disruption of a modestly stenotic vulnerable plaque, not visible by x-ray angiography, which results in a thrombotic complication (AHA plaque type VI). During its evolution, a type Va plaque may also become fibrotic (AHA plaque type Vc) or calcified (AHA plaque type Vb).2,3⇓ In contrast to coronary artery vulnerable plaques characterized by high lipid content and a thin fibrous cap, high-risk plaques of the carotid arteries tend to be fibrotic and severely stenotic.3 ### Imaging of Atherothrombotic Disease Because there is striking heterogeneity in the composition of human atherothrombotic plaques, even within the same individual, reliable noninvasive imaging tools that can detect early atherothrombotic disease in the various regions and characterize the composition of the plaques are clinically desirable.3 Such imaging tools would improve our understanding of the pathophysiological mechanisms underlying atherothrombotic processes and allow us to better risk-stratify the disease. Additionally, such tools may permit optimal tailoring of treatment and allow direct monitoring of the vascular response. Presently, a number of imaging modalities are employed to study atherosclerosis; most identify luminal diameter or stenosis, wall thickness, and plaque volume.3 Two noninvasive imaging modalities, computed tomography and MRI, have been introduced to the study …

488 Ultrasonographic features of plaque texture are associated with histological features of Carotid plaque instability

To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

PurposeEmbolic stroke of undetermined source (ESUS) is a subset of cryptogenic stroke constituting a large proportion of acute ischemic strokes. This study aimed to assess the features of non-stenotic carotid plaque (<50%) on computed tomographic angiography (CTA) and to evaluate the association between non-stenotic carotid plaque and ESUS.MethodsFrom January 1 to December 31, 2019, a total of 60 consecutive patients with primary unilateral ESUS and <50% carotid artery stenosis, as determined using screening ultrasonography, were hospitalized in the Department of Neurology of our hospital. All enrolled patients underwent CTA to determine the composition and morphological features of non-stenotic carotid plaques using consecutive sections in both carotid arteries. The features of these plaques with and without ipsilateral stroke in patients with ESUS were compared.ResultsSixty ESUS images were included in the study, with 85 plaques. Forty-five (52.9%) of these plaques were ipsilateral and 40 (47.1%) were contralateral to the stroke. Compared to that of the contralateral plaque group, the maximum carotid plaque thickness and plaque length of the ipsilateral group were greater (2.1 mm vs. 1.5 mm, p = 0.03; 20.8 mm vs. 12.1 mm, p = 0.02); however, there were no significant differences in the degree of luminal stenosis, presence of soft plaque and calcified plaque, and the number of ulcers on the plaque surface between the two groups. Similarly, the number of plaques with thickness >3 mm in the ipsilateral group was greater than in the contralateral group (30 vs. 13, p = 0.01). A lipid core was more common in individuals with ipsilateral strokes than in those with contralateral strokes (19 vs. 7, p = 0.02). Regression analysis showed that plaque lipid core area was an independent risk factor for ESUS (odds ratio, 1.92; 95% confidence interval, 1.22–3.04; p = 0.03).ConclusionsNon-stenotic carotid plaques could be an etiology of acute ischemic strokes classified as ESUS. The presence of a lipid core was a risk factor in individuals with non-stenotic carotid plaques.

Carotid plaque morphology assessed through high resolution ultrasound is nowadays an important diagnostic approach in the evaluation of stroke risk. The literature describes several methods for the characterization of plaque echogenicity and texture by using overall statistics across the carotid plaques. However, this averaged indicators may not be enough for a correct diagnosis of plaque instability. Therefore, it has been suggested that a local characterization of plaque morphology, where the extension and location of vulnerable regions inside the plaques is taken into account, could lead to significant improvements in the assessment of stroke risk. In this paper, a new method to characterize the morphology of carotid plaques in three-dimensions (3D) is proposed. The local characterization of carotid plaques is performed by using a 3D Graph-Cuts (GraphC) robust labeling method. This methodology allows to binary segment the data by minimizing an energy function that uses spatial correlation among neighboring pixels/voxels in order to remove small misclassified regions. The method is efficient since it is able to find the global minimum of the energy function in a very short time interval. Results show that this labeling procedure is less noisier and favors clustering, being more meaningful from a clinical point of view than the one obtained with simple thresholding. This paper shows that the use of GraphC may improve the 3D morphological characterization of carotid plaques, namely by providing a more appropriate identification of unstable foci inside the plaque.

Objective To investigate the relationship between the carotid intima-media thickness （IMT）, the characterization of atherosclerotic plaque as well as the degree of carotid stenosis and ischemic stroke. Methods The patients with first-ever acute ischemic stroke （ischemic stroke group） detected by color Doppler ultrasonography and the outpatients and hospitalized patients without ischemic stroke in the same period （control group） were collected retrospectively. The demographic data, vascular risk factors, and characterization of atherosclerotic plaque were compared between the two groups. Ischemic stroke group was divided into stroke subtype groups according to the TOAST classification. Their characteristics of carotid atherosclerosis were compared. Results A total of 200 patients with lust-ever acute ischemic stroke and 200 patients without ischemic stroke were included in the study. The carotid IMT in the ischemic stroke group was significantly thicker than that in the control group （left side： 1.04± 0.22mmvs. 0.69± 0.13mm, t= 7.34, P〈 0.01; right side： 1.05± 0. 21 mm vs. 0. 71 ± 0. 16 mm, t = 7. 43, P 〈 0. 01 ）. The proportions of the patients with moderate and severe stenosis were significantly higher （moderate stenosis： 38% vs. 14% ,X^2 = 7. 64, P 〈 0. 01 ; severe stenosis： 27% vs. 6%, X^2 = 7. 93, P 〈 0. 01 ）, and the proportion of patients with mild stenosis was no significant difference. The detection rate of carotid plaque in the ischemic stroke group was significantly higher than that in the control group （87. 0% vs. 31.5% ,X^2 =7. 01, P 〈0. 01）. The numbers of unstable plaque （lipid soft plaque, flat plaque, and mixed plaque） in the ischemic stroke group were 301 （65.3%）, and significantly more than 65 （31.7%） in the control group （X^2 =6. 30, P〈0. 01）. There was no significant difference in the distribution of carotid plaque between the two groups. The plaques were most common at the carotid artery bifurcation. Compared with those in other stroke subtypes, such as cardioem- bolism, small-vessel occlusion, stroke of other determined etiology, and stroke of undetermined etiology, the carotid IMT （left side： F=22. 34, P〈0. 01; right side： F =21.41, P 〈0. 01）, and the proportion of lipid soft plaque 0（2 =7. 93,P 〈0. 01）, carotid severe stenosis （X^2 =6. 83, P 〈 0. 01）, carotid occlusion （X^2 = 14. 00,P 〈0. 01） in stroke patients with large-artery atherosclerosis were significantly increased. Conclusions Carotid IMT, the numbers of unstable plaque as well as the degree of carotid stenosis were associated with the occurrence of ischemic stroke. Key words: Atherosclerosis; Carotid stenosis; Stroke; Brain ischemia; Risk Factors; Ultrasonography, Doppler; Risk factors

Introduction: The potential involvement of c-reactive protein (CRP), interleukin (IL)-6 and intracellular adhesion molecule (ICAM)-1 in the destabilization, erosion, or rupture of arterial plaque, particularly plaques in the lower extremity arteries is not well-established. Thus, we sought to determine whether circulating levels of CRP, IL-6, and ICAM-1 were associated with the presence, burden, and characteristics of femoral artery plaques. Methods: The San Diego Population Study is a prospective, population-based, multi-ethnic cohort of 1103 men and women averaged age 70 at a follow up exam taking place from 2007-11. At this exam, B-mode ultrasound was used to measure plaque presence, burden, and characteristics, including total plaque area (TPA), mean grey-scale median (GSM), and presence of calcification. Plaques were assessed in the left and right superficial and common femoral arteries. Plaque presence was defined as any plaque in any arterial segment, while plaque burden was total number of plaques summed over all four segments. Circulating CRP, ICAM-1, and IL-6 were also measured at this exam. Associations of CRP, IL-6, and ICAM-1 with plaque presence and burden were assessed using logistic and zero-inflated Poisson regression, respectively. Among those with plaque, linear and logistic regression were used to assess associations of the biomarkers with plaque characteristics. All models adjusted for age, sex, race/ethnicity, BMI, BP, statin use, smoking status, diabetes, peripheral artery disease, and chronic kidney disease. Results: Higher circulating CRP was significantly associated with plaque presence with participants in the highest quartile of CRP having 1.8 times higher odds of having femoral plaque compared to those in the lowest quartile. Participants in the highest quartiles of CRP and IL-6 were significantly more likely to have greater plaque burden compared to those in the lowest quartiles (CRP OR=1.64, 95% CI=1.09-2.44; IL-6 OR=1.65, 95%CI=1.06-2.55). No associations were observed between circulating biomarkers and plaque characteristics, including TPA, GSM, or calcification. Conclusions: Higher levels of circulating CRP and IL-6 are associated with greater plaque burden in the femoral arteries of participants in the SDPS; however, these biomarkers do not appear to be associated with characteristics of femoral artery plaques. These results are consistent with findings in the carotid and coronary arteries.

Non-invasive Carotid Artery Imaging to Identify the Vulnerable Plaque: Current Status and Future Goals

Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study

We hypothesized that women are more prone to develop coronary dissections during PCI due to potential balloon-oversizing or gender specific plaque and vascular characteristics. To date, a gender related difference in edge dissection has not been systematically studied. The Massachusetts General Hospital Optical Coherence Tomography (MGH OCT) Registry is an international registry of patients undergoing OCT procedures. We identified 206 consecutive patients (159 men, 47 women) with stable or unstable coronary syndromes demonstrating adequate OCT images for gender specific comparison in areas of non-overlapping stents. Presence of proximal edge dissection, its characteristics, plaque composition at stent borders and luminal diameters were assessed. A multivariate logistic regression model was applied to determine if female gender was predictive of proximal coronary dissection after adjusting for clinical, procedural and plaque characteristics. Proximal coronary dissection was significantly more common in women as compared to men (30.6 vs 15.6%, p = 0.02). No gender differences were observed in age, presentation, and stents per patient or plaque characteristics. The characteristics of edge dissections were different in women compared to men with a significant female predisposition to more complex proximal coronary dissection. In multivariable analysis, female gender was not a predictor of coronary dissection; on the other hand, stent oversizing and especially lipid rich plaque at proximal edge were independent predictors of proximal dissection. OCT confirms that female gender is associated with a greater than twofold increased risk of developing proximal coronary edge dissections as compared to men. But, the most potent independent predictor of proximal coronary edge dissection is the presence of a proximal lipid rich plaque.

Residual inflammation in cardiovascular organs is thought to be one of the catalysts for the increased risk of cardiovascular complications seen following pneumonia. To test this hypothesis, we investigated changes in plaque characteristics and inflammatory features in ApoE−/− mouse aorta and heart following pneumonia. Male ApoE−/− mice were fed a high fat diet for 8 weeks before intranasal inoculation with either Streptococcus pneumoniae serotype 4 (test group) or phosphate buffered saline (control group). Mice were sacrificed at 2-, 7- and 28-days post-challenge. Changes in plaque burden and characteristics in aortic root and thoracic aorta were characterized by Oil red O and Trichrome stains. Inflammatory changes were investigated by FDG-PET imaging and immunofluorescence staining. We found TIGR4-infected mice present with increased plaque presence in the aortic root and thoracic aorta at 2- and 28-days post-inoculation, respectively. Aortic wall remodelling was also more pronounced in mice challenged with pneumococci at 28 days post-inoculation. Aortic root plaques of infected mice had reduced collagen and smooth muscle cells, consistent with an unstable plaque phenotype. Pneumonia alters plaque burden, plaque characteristics, and aortic wall remodelling in ApoE−/− mice. These effects caused by Streptococcus pneumoniae TIGR4, may contribute to the increased risk of cardiovascular complications seen in survivors of this infection.

Quantitative and Qualitative Analysis of Atherosclerotic Stenosis in the Middle Cerebral Artery Using High-Resolution Magnetic Resonance Imaging.

<h3>Purpose</h3> During carotid angioplasty and stenting (CAS), hemodynamic instability (HDI) can occur, possibly causing post-procedural ischemic complications. The goal of this study was to investigate the risk factors of HDI focusing on characteristics of plaque. <h3>Materials and methods</h3> Thirty nine CAS patients were retrospectively evaluated for HDI. Prolonged HDI that lasted over 30 min was analyzed in relation to characteristics of calcified plaque. <h3>Results</h3> Nineteen (48.7%) patients had HDI. Ten of the 19 had both bradycardia and hypotension, and nine had only bradycardia. All bradycardia was treated well with a transcutaneous temporary cardiac pacemaker. But eight patients presented with prolonged hypotension in spite of recovery of bradycardia. Calcified plaque was a related factor associated with HDI (odds ratio, 8.571; 95% confidence interval, 1.321–55.62; p = 0.024). Extensive and eccentric type calcified plaques were associated with prolonged hypotension (p = 0.04, and p = 0.028, respectively). <h3>Conclusion</h3> The calcification of plaque is a predictable factor of HDI during CAS, and its extensive and eccentric calcified plaques may be related to prolonged HDI. <h3>Disclosures</h3> S. Sheen: None. B. Chung: None. J. Choi: None.

IntroductionTo investigate the structural characteristics and its clinical significant of angiographic contrast materiel drain-lagged coronary segments.Materials and methods23 segments coronary arteries in 20 patients with angiographic contrast materiel drain-lagged were...