Predictive value of spiral shape in coronary plaque progression: an intraindividual comparative study.

OBJECTIVE: We conducted a pilot study to explore the value of spiral-shaped sign of plaque from coronary computed tomographic angiography (CCTA) in predicting plaque progression by intraindividual comparison. METHODS: A total of 30 patients with a total of 60 plaques who received serial CCTA were retrospectively included and intraindividual compared. The spiral shape was defined as plaques coursing along the long axis of a coronary artery and encircling it at an angle of ≥ 180 degrees. The high-risk and other plaque signs were recorded. RESULTS: On baseline CCTA, the spiral shape (P < 0.01) and length (P < 0.05) of plaques were more frequently seen in the progression group than in the nonprogression group; however, there was no difference between two groups in terms of high-risk plaque signs. In the progression group, plaque length, volume, and napkin-ring sign on follow-up CCTA were significantly greater than at baseline (P < 0.05). In the nonprogression group, there were fewer low-attenuation and positive remodeling plaques on follow-up CCTA than at baseline (P < 0.05). The spiral shape (standardized ß = -4.55; P < 0.01) was an independent risk factor for plaque progression. There were 24 spiral plaques in the progression group, of which 16 (66.7%) had progression below the twist point of the spiral shape. CONCLUSIONS: The baseline spiral shape is more frequently found in those lesions that progress than in those that do not in patients with multiple coronary lesions, and the spiral shape is an independent predictor of which plaques will progress.

Classification of moving coronary calcified plaques based on motion artifacts using convolutional neural networks: a robotic simulating study on influential factors.

BACKGROUND: Motion artifacts affect the images of coronary calcified plaques. This study utilized convolutional neural networks (CNNs) to classify the motion-contaminated images of moving coronary calcified plaques and to determine the influential factors for the classification performance. METHODS: Two artificial coronary arteries containing four artificial plaques of different densities were placed on a robotic arm in an anthropomorphic thorax phantom. Each artery moved linearly at velocities ranging from 0 to 60 mm/s. CT examinations were performed with four state-of-the-art CT systems. All images were reconstructed with filtered back projection and at least three levels of iterative reconstruction. Each examination was performed at 100%, 80% and 40% radiation dose. Three deep CNN architectures were used for training the classification models. A five-fold cross-validation procedure was applied to validate the models. RESULTS: The accuracy of the CNN classification was 90.2 ± 3.1%, 90.6 ± 3.5%, and 90.1 ± 3.2% for the artificial plaques using Inception v3, ResNet101 and DenseNet201 CNN architectures, respectively. In the multivariate analysis, higher density and increasing velocity were significantly associated with higher classification accuracy (all P < 0.001). The classification accuracy in all three CNN architectures was not affected by CT system, radiation dose or image reconstruction method (all P > 0.05). CONCLUSIONS: The CNN achieved a high accuracy of 90% when classifying the motion-contaminated images into the actual category, regardless of different vendors, velocities, radiation doses, and reconstruction algorithms, which indicates the potential value of using a CNN to correct calcium scores.

Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data.

Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm3), with necrotic core and fibro-fatty PV regression (- 5.7 mm3 and - 5.6 mm3, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm3). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm3). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm3), predominantly increasing in calcified PV (+ 35.9 mm3). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.

Morphological Plaque Characteristics and Clinical Outcomes in Patients With Acute Coronary Syndrome and a Cancer History.

Background Although patients with a cancer history have a 2 to 3 times higher risk for acute coronary syndrome (ACS), the morphological characteristics of ACS culprit plaque in those patients and their relations with clinical outcomes remain unknown. Methods and Results This retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent optical coherence tomography-guided emergent percutaneous coronary intervention. Patients were categorized into those without a cancer history, those with a cancer history, and those currently receiving cancer treatment. ACS culprit lesions were classified as plaque rupture, plaque erosion, or calcified nodule using optical coherence tomography. Plaque erosion frequency was significantly higher in culprit lesions of patients with current cancer and patients with cancer history than in those of patients without cancer history (56.3% versus 61.7% versus 36.5%). Calcified nodule incidence was significantly higher in patients without cancer history than in patients with current cancer and patients without cancer history (patients with current cancer: 12.4% versus patients without cancer history: 25.5% versus patients without cancer history: 12.6%, P<0.001). Cancer history was independently associated with nonplaque rupture (plaque erosion or calcified nodule) in ACS culprit lesions (odds ratio, 4.00; P<0.001). Cancer history was independently associated with major adverse cardiovascular events (hazard ratio [HR], 1.98; P=0.002). Nonplaque rupture in ACS culprit lesions was independently associated with major adverse cardiovascular events (HR, 1.60; P=0.011). Conclusions Patients with a cancer history had significantly worse clinical outcomes after ACS than those without a cancer history. Those with a cancer history had significantly higher plaque erosion and calcified nodule incidences in the ACS culprit lesions, which might partly explain their worse clinical outcomes. Registration URL: www.umin.ac.jp/ctr/index.htm. Unique Identifier: UMIN000038442.

Symptomatic nonstenotic carotid disease: Evaluation of a proposed classification scheme in a prospective cohort.

INTRODUCTION: Unraveling symptomatic nonstenotic carotid disease (SyNC) as a stroke etiology from other cryptogenic stroke may have important implications for defining natural history and for tailoring secondary prevention strategies. We aim to describe the characteristics of the plaques in a prospectively-collected cohort of patients with non-invasive imaging suggesting symptomatic carotid stenosis but whose DSA demonstrated nonstenotic atheromatous disease, and to evaluate the recurrence rate depending on the type of SyNC. METHODS: We reviewed prospectively-collected data for patients presenting with new neurologic events and non-invasive imaging suggestive of moderate or severe (≥50%) carotid stenosis between July 2016 and October 2018. Patients were included in the present study if the degree of stenosis on DSA was < 50%. We assigned these patients into groups based on a previously-proposed working definition of SyNC, and analyzed the rate of recurrent stroke in the following 6 months. RESULTS: 28 patients had DSA-confirmed < 50% stenosis and constituted the study cohort. The median age was 73 years and 64% were male; median presenting NIHSS was 1 (IQR 0-3). The great majority (86%) of carotid plaques had high-risk features including ulcerated plaque (n = 21, 75%) and plaque > 3 mm thick (n = 18, 64%). 17 of 28 patients (61%) met classification criteria for "definite" or "probable" SyNC. Three of five patients in the "definite SyNC" group experienced recurrent neurologic events. CONCLUSION: The majority of patients with non-invasive imaging suggesting carotid stenosis harbor symptomatic carotid disease per current classifications despite DSA stenosis < 50%. Current classification schema may allow for risk stratification of SyNC patients and these findings warrant further study.

Fully automated plaque characterization in intravascular OCT images using hybrid convolutional and lumen morphology features.

For intravascular OCT (IVOCT) images, we developed an automated atherosclerotic plaque characterization method that used a hybrid learning approach, which combined deep-learning convolutional and hand-crafted, lumen morphological features. Processing was done on innate A-line units with labels fibrolipidic (fibrous tissue followed by lipidous tissue), fibrocalcific (fibrous tissue followed by calcification), or other. We trained/tested on an expansive data set (6,556 images), and performed an active learning, relabeling step to improve noisy ground truth labels. Conditional random field was an important post-processing step to reduce classification errors. Sensitivities/specificities were 84.8%/97.8% and 91.4%/95.7% for fibrolipidic and fibrocalcific plaques, respectively. Over lesions, en face classification maps showed automated results that agreed favorably to manually labeled counterparts. Adding lumen morphological features gave statistically significant improvement (p < 0.05), as compared to classification with convolutional features alone. Automated assessments of clinically relevant plaque attributes (arc angle and length), compared favorably to those from manual labels. Our hybrid approach gave statistically improved results as compared to previous A-line classification methods using deep learning or hand-crafted features alone. This plaque characterization approach is fully automated, robust, and promising for live-time treatment planning and research applications.

Automated plaque classification using computed tomography angiography and Gabor transformations.

Cardiovascular diseases are the primary cause of death globally. These are often associated with atherosclerosis. This inflammation process triggers important variations in the coronary arteries (CA) and can lead to coronary artery disease (CAD). The presence of CA calcification (CAC) has recently been shown to be a strong predictor of CAD. In this clinical setting, computed tomography angiography (CTA) has begun to play a crucial role as a non-intrusive imaging method to characterize and study CA plaques. Herein, we describe an automated algorithm to classify plaque as either normal, calcified, or non-calcified using 2646 CTA images acquired from 73 patients. The automated technique is based on various features that are extracted from the Gabor transform of the acquired CTA images. Specifically, seven features are extracted from the Gabor coefficients : energy, and Kapur, Max, Rényi, Shannon, Vajda, and Yager entropies. The features were then ordered based on the F-value and input to numerous classification methods to achieve the best classification accuracy with the least number of features. Moreover, two well-known feature reduction techniques were employed, and the features acquired were also ranked according to F-value and input to several classifiers. The best classification results were obtained using all computed features without the employment of feature reduction, using a probabilistic neural network. An accuracy, positive predictive value, sensitivity, and specificity of 89.09%, 91.70%, 91.83% and 83.70% was obtained, respectively. Based on these results, it is evident that the technique can be helpful in the automated classification of plaques present in CTA images, and may become an important tool to reduce procedural costs and patient radiation dose. This could also aid clinicians in plaque diagnostics.

Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS.

BACKGROUND: Branch atheromatous disease (BAD) is distinctive from large and small arterial diseases, which is single subcortical infarction larger than lacunar stroke in the territories of deep perforators without relevant arterial stenosis. BAD meets the current criteria of embolic stroke of undetermined source. We performed an exploratory analysis of BAD in patients recruited to NAVIGATE embolic stroke of undetermined source, a randomized controlled trial to compare rivaroxaban and aspirin in embolic stroke of undetermined source patients. METHODS AND RESULTS: Among 3972 stroke patients in cerebral hemispheres with intracranial arterial imaging, 502 (12.6%) patients met the criteria for BAD. BAD was associated with younger age (years; OR: 0.97, 95% CI: 0.96-0.98), race (Asian; OR: 1.78, 95% CI: 1.44-2.21), region (Eastern Europe; OR: 2.49, 95% CI: 1.87-3.32), and higher National Institute of Health Stroke Scale (OR: 1.17, 95% CI: 1.12-1.22) at randomization. During follow-up, stroke or systemic embolism (2.5%/year vs. 6.2%/year, p = 0.0022), stroke (2.1%/year vs. 6.2%/year, p = 0.0008), and ischemic stroke (2.1%/year vs. 5.9%/year, p = 0.0013) occurred less frequently in BAD than non-BAD patients. There were no differences in annual rates of stroke or systemic embolism (2.5%/year vs. 2.5%/year, HR: 1.01, 95% CI: 0.33-3.14) or major bleeding (1.3%/year vs. 0.8%/year, HR: 1.51, 95% CI: 0.25-9.05) between rivaroxaban and aspirin groups among BAD patients. CONCLUSIONS: BAD was relatively common, especially in Asian and from Eastern Europe among embolic stroke of undetermined source patients. Stroke severity was higher at randomization but recurrence of stroke was fewer in BAD than non-BAD patients. The efficacy and safety of rivaroxaban and aspirin did not differ among BAD patients.

An automatic multi-class coronary atherosclerosis plaque detection and classification framework.

Detection of different classes of atherosclerotic plaques is important for early intervention of coronary artery diseases. However, previous methods focused either on the detection of a specific class of coronary plaques or on the distinction between plaques and normal arteries, neglecting the classification of different classes of plaques. Therefore, we proposed an automatic multi-class coronary atherosclerosis plaque detection and classification framework. Firstly, we retrieved the transverse cross sections along centerlines from the computed tomography angiography. Secondly, we extracted the region of interests based on coarse segmentation. Thirdly, we extracted a random radius symmetry (RRS) feature vector, which incorporates multiple descriptions into a random strategy and greatly augments the training data. Finally, we fed the RRS feature vector into the multi-class coronary plaque classifier. In experiments, we compared our proposed framework with other methods on the cross sections of Rotterdam Coronary Datasets, including 729 non-calcified plaques, 511 calcified plaques, and 546 mixed plaques. Our RRS with support vector machine outperforms the intensity feature vector and the random forest classifier, with the average precision of 92.6 ± 1.9% and average recall of 94.3 ± 2.1%. The proposed framework provides a computer-aided diagnostic method for multi-class plaque detection and classification. Graphical abstract Diagram of the proposed automatic multi-class coronary atherosclerosis plaque detection and classification framework. ᅟ.

In vivo vulnerability grading system of plaques causing acute coronary syndromes: An intravascular imaging study.

BACKGROUND: Autopsy studies shed light on the interplay between fatal acute coronary syndromes (ACS) and features of plaque vulnerability. This is a prospective pilot study designed for generating a new in vivo imaging grading system of plaque vulnerability. METHODS: We studied 87 coronary vessels in 63 consecutive patients: 48 with Acute Coronary Syndrome (ACS) and 15 with stable coronary artery disease using IntraVascular-Ultrasound Near-Infrared-Spectroscopy (IVUS-NIRS) and Optical Coherence Tomography (OCT). We identified 99 lesions: 21 were the ACS culprit lesions (18 ulcerations and 3 with intact fibrous cap), 78 were non-culprit lesions including plaques located in the same ACS culprit vessel (N12), plaques located in a non-culprit vessel in patients with ACS (28) and target lesions of stable patients (N 38). A second analysis focused on lipid plaques, comparing the 18 ACS culprit ulcerated lesions and the 55 non-culprit lesions. RESULTS: The co-presence of the following three features of vulnerability [Minimal Luminal Area (MLA) <4 mm2, Fibrous Cap Thickness (FCT) < 75 µm and superficial macrophages] was by far more frequent in ACS culprit lesions than in controls (OR 40.6 for all lesions and OR 45.7 for ulcerated culprit lesions only). The triple-feature OCT grading identified vulnerable plaques with a much higher accuracy than that obtained applying each single feature of vulnerability. CONCLUSIONS: The co-presence of the 3 OCT features of vulnerability (MLA < 4 mm2, FCT < 75 µm and superficial macrophages) identifies culprit ACS lesions with a very high odd ratio. This finding could set the basis for a new OCT vulnerability grading system including superficial macrophages.

TIA patients with higher ABCD3-I scores are prone to a higher incidence of intracranial stenosis, unstable carotid plaques and multiple-vessel involvement.

The ABCD3-I criteria have proved to be effective for use in regular clinical practice to assist in transient ischemic attack (TIA) risk stratification and treatment. In this prospective study we aimed to explore the relationships between risk stratification and arterial stenosis location, carotid plaque morphology and vessel involvement in 90 TIA patients, stratifying risk by ABCD3-I scores. Clinical variables such as total cholesterol, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin, homocysteine and high-sensitive C-reactive protein levels were recorded. The endpoint was subsequent stroke at seven-day follow-up. Ninety patients were divided into three risk groups on the basis of their ABCD3-I scores. The results revealed that patients with higher ABCD3-I scores showed a higher occurrence of intracranial stenosis (P < 0.05), less organized carotid plaques (P < 0.05) and multiple-vessel involvement (P < 0.05).

High Sensitivity Troponins Discriminate Different Morphologies of Coronary Artery Plaques Being Assessed by Coronary Computed Tomography Angiography.

BACKGROUND: This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) and the morphology of coronary artery plaques detected by coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD). METHODS: Patients undergoing CCTA were prospectively enrolled. CCTA was indicated by a low to intermediate pretest probability for CAD during routine clinical care. Within 24 hours of CCTA examination, peripheral blood samples were taken to measure hsTnI, hsTnT, and N-terminal probrain natriuretic peptide (NT-proBNP). RESULTS: A total of 99 patients were enrolled with 43% without CAD, 9% with noncalcified plaques, 28% with calcified plaques, and 19% with mixed type plaque lesions. Both hsTnI and hsTnT levels were able to discriminate significantly between the groups, especially in the presence of mixed coronary plaques (AUC range: 0.741-0.752; p = 0.0001). In multivariate logistic regression models, hsTnT, but not hsTnI, was still significantly associated with mixed coronary plaque morphology (odds ratio = 8.968; 95% CI 1.999-40.241; p = 0.004). CONCLUSIONS: Both hsTnI and hsTnT are able to discriminate between different coronary artery plaques morphologies, whereas hsTnT was significantly associated with mixed coronary plaques in patients with suspected CAD. This trial is registered with NCT03074253.

[Diagnostic value of carotid atherosclerosis score for ischemic stroke].

OBJECTIVE: To discuss the diagnostic value of carotid atherosclerosis score for ischemic stroke. METHODS: In the study, 151 patients with ischemic stroke were enrolled, who were diagnosed by cranial CT scan or cranial MRI scan, and examined with carotid duplex ultrasound, and 151 healthy check-up cases matched by age and sex were chosen as control group, who were excluded ischemic stroke by cranial CT scan or cranial MRI scan. All the control cases were examined with carotid duplex ultrasound also. Intima-media thickness (IMT), the number of carotid plaques, the size of each plaque, the location of the plaque and each plaque's echo, texture, surface regularity were estimated by carotid duplex ultrasound. RESULTS: The IMT of the case group and the control group were (0.946±0.185) mm and (0.863±0.148) mm, and there were significant differences (P<0.001); The parameters of arterial plaque correlated with ischemic stroke were plaque's echo, texture and surface regularity, however the plaque size and location were not correlated with ischemic stroke. The median and quartile of carotid artery plaque score were 3 and 2 respectively in case group, 1 and 2 respectively in control group, and there were significant differences (P<0.001); The parameters of carotid arterial atherosclerosis associated with ischemic stroke were carotid artery plaque score,carotid stenosis degree and IMT, but not the number of carotid plaques. The median and quartile of carotid arterial atherosclerosis score were 5 and 4 respectively in case group, 2 and 4 respectively in control group, and there were significant differences (P<0.001); The area under the curve (AUC) for IMT, the number of carotid plaques, carotid artery plaque score and carotid arterial atherosclerosis score were 0.679, 0.677, 0.704 and 0.805,respectively (P<0.001). The accuracy of carotid atherosclerosis score was the highest. CONCLUSION: Carotid artery plaque score and carotid atherosclerosis score can be used for the diagnosis of ischemic stroke, and the accuracy of carotid atherosclerosis score is higher.

Ex-vivo imaging and plaque type classification of intracranial atherosclerotic plaque using high resolution MRI.

BACKGROUND AND AIMS: Recent development of high resolution MRI techniques have enabled imaging of intracranial atherosclerotic plaque in vivo. However, identifying plaque composition remains challenging given the small size and the lack of histological validation. This study aims to quantify the relaxation times of intracranial plaque components ex vivo at 3 T and to determine whether multi-contrast MRI could classify intracranial plaque according to the American Heart Association classification with histological validation. METHODS: A total of 53 intracranial arteries with atherosclerotic plaques from 20 cadavers (11 male, age 73.8 ± 10.9) were excised. Quantitative T1/T2/T2* mapping sequences and multi-contrast fast-spin echo sequences (T1, T2, proton-density weighted and short time inversion recovery) were acquired. Plaque components including: fibrous cap, lipid core, fibrous tissue, calcification, and healthy wall were segmented on histology, and their relaxation times were derived from quantitative images. Two radiologists independently classified plaque type blinded to the histology results. RESULTS: Relaxation times of plaque components are distinct and different. T2 and T2* values of lipid core are lower than fibrous cap (p = 0.026 & p < 0.0001), but are comparable with fibrous tissue and healthy wall (p = 0.76 & p = 0.42). MRI reliably classified plaque type compared with histology (κ = 0.69) with an overall accuracy of 80.7%. The sensitivity and specificity using MRI to identify fibro-lipid atheroma (type IV-V) was 94.8% and 77.1%, respectively. Inter-observer agreement was excellent (κ = 0.77). CONCLUSION: Intracranial plaque components have distinct and different relaxation times at 3 T. High-resolution MRI is able to characterize intracranial plaque composition and classify plaque types ex vivo at 3 T.

The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes.

Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice.

Trends in Coronary Atherosclerosis: A Tale of Two Population Subgroups.

BACKGROUND: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined. The present investigation of coronary artery disease trends for the period 1995 through 2012 was prompted by a desire for more detailed examination of more recent coronary artery disease trends in light of reports that the epidemics of obesity and diabetes have slowed and are perhaps ending. METHODS: This population-based series of cross-sectional investigations identified all Olmsted County, Minnesota residents aged 16-64 years who died 1995 through 2012 (N = 2931). For decedents with nonnatural manner of death, pathology reports were reviewed for grade of atherosclerosis assigned each major epicardial coronary artery. Using logistic regression, we estimated calendar-year trends in grade (unadjusted and age- and sex-adjusted) for each artery, initially as an ordinal measure (range, 0-4); then, based on evidence of nonproportional odds, as a dichotomous variable (any atherosclerosis, yes/no) and as an ordinal measure for persons with atherosclerosis (range, 1-4). RESULTS: Of 474 nonnatural deaths, 453 (96%) were autopsied; 426 (90%) had coronary stenosis graded. In the ordinal-logistic model for trends in coronary artery disease grade (range, 0-4), the proportional odds assumption did not hold. In subsequent analysis as a dichotomous outcome (grades 0 vs 1-4), each artery exhibited a significant temporal decline in the proportion with any atherosclerosis. Conversely, for subjects with coronary artery disease grade 1-4, age- and sex-adjusted ordinal regression revealed no change over time in 2 arteries and statistically significant temporal increases in severity in 2 arteries. CONCLUSIONS: Findings suggest that efforts to prevent coronary artery disease onset have been relatively successful. However, statistically significant increases in the grade of atherosclerosis in 2 arteries among persons with coronary artery disease may be indicative of a major public health challenge.

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

OBJECTIVES: To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. METHODS: Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. RESULTS: A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. CONCLUSIONS: These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. KEY POINTS: • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

Vascular calcification in atherosclerosis: potential roles of macrophages and non-coding micro-RNAs / Calcificación vascular en aterosclerosis: posibles funciones de macrófagos y micro-ARNs no codificantes

Coronary heart disease, a leading cause of death in western societies, is caused by the presence of atherosclerotic plaques in the coronary arteries. Calcification is a frequent complication of atherosclerotic plaques, and often a contributing factor to their instability and rupture. Endothelial cells, smooth muscle cells and plaque macrophages, all contribute to the calcification process, which is reminiscent of that underlying bone formation. In particular, the role of macrophages in calcification has long been recognized, but whether or not distinct macrophage subsets ­v.g., M1 or inflammatory, and M2 or antinflammatory have specific functions in osteogenic signaling within the context of plaque calcification remains poorly understood. Over the past few years, accumulated evidence has revealed novel roles of non-coding micro-RNAs (miRs) in atherorelevant functions of macrophages and in mechanisms linked to macrophage divergence into different subtypes. In this article we discuss some salient findings on potential roles of miRs in vascular calcification, with focus on those miRs that have also been associated to macrophage differentiation, and speculate on their potential relation to M1 and M2 macrophages in the context of calcification of atherosclerotic plaques. (AU)

La enfermedad cardíaca coronaria, principal causa de muerte en occidente, es causada por la presencia de placas ateroscleróticas en las arterias coronarias. La presencia de depósitos de calcificación es una complicación frecuente de la placa, y puede contribuir a la inestabilidad y ruptura de la misma. El proceso de calcificación de la placa es similar al que ocurre en hueso, y contribuyen al mismo, mecanismos dependientes de células endoteliales, células musculares lisas y macrófagos, células que están presentes en todas las etapas de desarrollo de la placa aterosclerótica. El rol de los macrófagos en la calcificación de la placa se conoce desde hace tiempo, pero la contribución de los distintos tipos de macrófagos ­por ejemplo, M1 o tipo inflamatorio, y M2 o tipo antiinflamatorio a mecanismos de señalización osteogénica en dicho contexto aún no se conoce. Recientemente varios trabajos experimentales han revelado la existencia de nuevos roles de micro-ARNs no codificantes (miRs) en varias funciones de los macrófagos que son de relevancia en el proceso aterogénico, como así también en mecanismos relacionados a la diferenciación de macrófagos en subtipos específicos. En este artículo discutimos algunos de los hallazgos más importantes sobre posibles nuevos roles de miRs en calcificación vascular, poniendo énfasis en aquellos miRs que han sido también asociados a la diferenciación de macrófagos, y especulamos acerca de su posible relación con macrófagos M1 y M2 en el contexto de la calcificación de la placa aterosclerótica. (AU)

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.