Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Recent advances in vascular ultrasound imaging technology and their clinical implications.

In this paper recent advances in vascular ultrasound imaging technology are discussed, including three-dimensional ultrasound (3DUS), contrast-enhanced ultrasound (CEUS) and strain- (SE) and shear-wave-elastography (SWE). 3DUS imaging allows visualisation of the actual 3D anatomy and more recently of flow, and assessment of geometrical, morphological and mechanical features in the carotid artery and the aorta. CEUS involves the use of microbubble contrast agents to estimate sensitive blood flow and neovascularisation (formation of new microvessels). Recent developments include the implementation of computerised tools for automated analysis and quantification of CEUS images, and the possibility to measure blood flow velocity in the aorta. SE, which yields anatomical maps of tissue strain, is increasingly being used to investigate the vulnerability of the carotid plaque, but is also promising for the coronary artery and the aorta. SWE relies on the generation of a shear wave by remote acoustic palpation and its acquisition by ultrafast imaging, and is useful for measuring arterial stiffness. Such advances in vascular ultrasound technology, with appropriate validation in clinical trials, could positively change current management of patients with vascular disease, and improve stratification of cardiovascular risk.

CurveletTransform-Based Texture Analysis of Carotid B-mode Ultrasound Images in Asymptomatic Men With Moderate and Severe Stenoses: A Preliminary Clinical Study.

The curvelet transform, which represents images in terms of their geometric and textural characteristics, was investigated toward revealing differences between moderate (50%-69%, n = 11) and severe (70%-100%, n = 14) stenosis asymptomatic plaque from B-mode ultrasound. Texture features were estimated in original and curvelet transformed images of atheromatous plaque (PL), the adjacent arterial wall (intima-media [IM]) and the plaque shoulder (SH) (i.e., the boundary between plaque and wall), separately at end systole and end diastole. Seventeen features derived from the original images were significantly different between the two groups (4 for IM, 3 for PL and 10 for SH; 9 for end diastole and 8 for end systole); 19 of 234 features (2 for IM and 17 for SH; 8 for end systole and 11 for end diastole) derived from curvelet transformed images were significantly higher in the patients with severe stenosis, indicating higher magnitude, variation and randomness of image gray levels. In these patients, lower body height and higher serum creatinine concentration were observed. Our findings suggest that (a) moderate and severe plaque have similar curvelet-based texture properties, and (b) IM and SH provide useful information about arterial wall pathophysiology, complementary to PL itself. The curvelet transform is promising for identifying novel indices of cardiovascular risk and warrants further investigation in larger cohorts.

Stratification of carotid atheromatous plaque using interpretable deep learning methods on B-mode ultrasound images.

Carotid atherosclerosis is the major cause of ischemic stroke resulting in significant rates of mortality and disability annually. Early diagnosis of such cases is of great importance, since it enables clinicians to apply a more effective treatment strategy. This paper introduces an interpretable classification approach of carotid ultrasound images for the risk assessment and stratification of patients with carotid atheromatous plaque. To address the highly imbalanced distribution of patients between the symptomatic and asymptomatic classes (16 vs 58, respectively), an ensemble learning scheme based on a sub-sampling approach was applied along with a two-phase, cost-sensitive strategy of learning, that uses the original and a resampled data set. Convolutional Neural Networks (CNNs) were utilized for building the primary models of the ensemble. A six-layer deep CNN was used to automatically extract features from the images, followed by a classification stage of two fully connected layers. The obtained results (Area Under the ROC Curve (AUC): 73%, sensitivity: 75%, specificity: 70%) indicate that the proposed approach achieved acceptable discrimination performance. Finally, interpretability methods were applied on the model's predictions in order to reveal insights on the model's decision process as well as to enable the identification of novel image biomarkers for the stratification of patients with carotid atheromatous plaque.Clinical Relevance-The integration of interpretability methods with deep learning strategies can facilitate the identification of novel ultrasound image biomarkers for the stratification of patients with carotid atheromatous plaque.

Motion synchronisation patterns of the carotid atheromatous plaque from B-mode ultrasound.

Asynchronous movement of the carotid atheromatous plaque from B-mode ultrasound has been previously reported, and associated with higher risk of stroke, but not quantitatively estimated. Based on the hypothesis that asynchronous plaque motion is associated with vulnerable plaque, in this study, synchronisation patterns of different tissue areas were estimated using cross-correlations of displacement waveforms. In 135 plaques (77 subjects), plaque radial deformation was synchronised by approximately 50% with the arterial diameter, and the mean phase shift was 0.4 s. Within the plaque, the mean phase shifts between the displacements of the top and bottom surfaces were 0.2 s and 0.3 s, in the radial and longitudinal directions, respectively, and the synchronisation about 80% in both directions. Classification of phase-shift-based features using Random Forests yielded Area-Under-the-Curve scores of 0.81, 0.79, 0.89 and 0.90 for echogenicity, symptomaticity, stenosis degree and plaque risk, respectively. Statistical analysis showed that echolucent, high-stenosis and high-risk plaques exhibited higher phase shifts between the radial displacements of their top and bottom surfaces. These findings are useful in the study of plaque kinematics.

Carotid Wall Longitudinal Motion in Ultrasound Imaging: An Expert Consensus Review.

Motion extracted from the carotid artery wall provides unique information for vascular health evaluation. Carotid artery longitudinal wall motion corresponds to the multiphasic arterial wall excursion in the direction parallel to blood flow during the cardiac cycle. While this motion phenomenon has been well characterized, there is a general lack of awareness regarding its implications for vascular health assessment or even basic vascular physiology. In the last decade, novel estimation strategies and clinical investigations have greatly advanced our understanding of the bi-axial behavior of the carotid artery, necessitating an up-to-date review to summarize and classify the published literature in collaboration with technical and clinical experts in the field. Within this review, the state-of-the-art methodologies for carotid wall motion estimation are described, and the observed relationships between longitudinal motion-derived indices and vascular health are reported. The vast number of studies describing the longitudinal motion pattern in plaque-free arteries, with its putative application to cardiovascular disease prediction, point to the need for characterizing the added value and applicability of longitudinal motion beyond established biomarkers. To this aim, the main purpose of this review was to provide a strong base of theoretical knowledge, together with a curated set of practical guidelines and recommendations for longitudinal motion estimation in patients, to foster future discoveries in the field, toward the integration of longitudinal motion in basic science as well as clinical practice.

AI in Medical Imaging Informatics: Current Challenges and Future Directions.

This paper reviews state-of-the-art research solutions across the spectrum of medical imaging informatics, discusses clinical translation, and provides future directions for advancing clinical practice. More specifically, it summarizes advances in medical imaging acquisition technologies for different modalities, highlighting the necessity for efficient medical data management strategies in the context of AI in big healthcare data analytics. It then provides a synopsis of contemporary and emerging algorithmic methods for disease classification and organ/ tissue segmentation, focusing on AI and deep learning architectures that have already become the de facto approach. The clinical benefits of in-silico modelling advances linked with evolving 3D reconstruction and visualization applications are further documented. Concluding, integrative analytics approaches driven by associate research branches highlighted in this study promise to revolutionize imaging informatics as known today across the healthcare continuum for both radiology and digital pathology applications. The latter, is projected to enable informed, more accurate diagnosis, timely prognosis, and effective treatment planning, underpinning precision medicine.

Ultrasound and Biochemical Diagnostic Tools for the Characterization of Vulnerable Carotid Atherosclerotic Plaque.

Stroke is a leading cause of morbidity and mortality worldwide, and characterization of vulnerable carotid plaque remains the spearhead of scientific research. Plaque destabilization, the key factor that induces the series of events leading to the clinical symptoms of carotid artery disease, is a consequence of complex mechanical, structural and biochemical processes. Novel imaging and molecular markers have been studied as predictors of disease outcome with promising results. The aim of this review is to present the current state of research on the association between ultrasound-derived echogenicity indices and blood parameters indicative of carotid plaque stability and activity. Bibliographic research revealed that there are limited available data. Among the biomarkers studied, those related to oxidative stress, lipoproteins and diabetes/insulin resistance are associated with echolucent plaques, whereas adipokines are associated with echogenic plaques. Biomarkers of inflammation and coagulation have not exhibited any conclusive relationship with plaque echogenicity, and it is not possible to come to any conclusion regarding calcification-, apoptosis- and neo-angiogenesis-related parameters because of the extremely limited bibliographic data.

Using ultrasound image analysis to evaluate the role of elastography imaging in the diagnosis of carotid atherosclerosis.

Valid characterization of carotid atherosclerosis (CA) is a crucial public health issue, which would limit the major risk held by CA for both patient safety and state economies. CA is typically diagnosed and assessed using duplex ultrasonography (US). Elastrography Imaging (EI) is a promising US technique for quantifying tissue elasticity (ES). In this work, we investigated the association between ES of carotid atherosclerotic lesions, derived from EI, and texture indices, calculated from US image analysis. US and EI images of 23 atherosclerotic plaques (16 patients) were analyzed. Texture features derived from US image analysis (Gray-Scale Median (GSM), plaque area (A) and co-occurrence-matrixderived features) were calculated. Statistical analysis revealed associations between US texture features and EI measured indices. This result indicates accordance in US and EI techniques and states the promising role of EI in diagnosis of CA.

Sleep EEG and spindle characteristics after combination treatment with clozapine in drug-resistant schizophrenia: a pilot study.

PURPOSE: Clozapine is an atypical neuroleptic agent, effective in treating drug-resistant schizophrenia. The aim of this work was to investigate overall sleep architecture and sleep spindle morphology characteristics, before and after combination treatment with clozapine, in patients with drug-resistant schizophrenia who underwent polysomnography. METHODS: Standard polysomnographic techniques were used. To quantify the sleep spindle morphology, a modeling technique was used that quantifies time-varying patterns in both the spindle envelope and the intraspindle frequency. RESULTS: After combination treatment with clozapine, the patients showed clinical improvement. In addition, their overall sleep architecture and, more importantly, parameters that quantify the time-varying sleep spindle morphology were affected. Specifically, the results showed increased stage 2 sleep, reduced slow-wave sleep, increased rapid eye movement sleep, increased total sleep time, decreased wake time after sleep onset, as well as effects on spindle amplitude and intraspindle frequency parameters. However, the above changes in overall sleep architecture were statistically nonsignificant trends. CONCLUSIONS: The findings concerning statistically significant effects on spindle amplitude and intraspindle frequency parameters may imply changes in cortical sleep EEG generation mechanisms, as well as changes in thalamic pacing mechanisms or in thalamo-cortical network dynamics involved in sleep EEG generation, as a result of combination treatment with clozapine. SIGNIFICANCE: Sleep spindle parameters may serve as metrics for the eventual development of effective EEG biomarkers to investigate treatment effects and pathophysiological mechanisms in schizophrenia.

A semantically-aided architecture for a web-based monitoring system for carotid atherosclerosis.

Carotid atherosclerosis is a multifactorial disease and its clinical diagnosis depends on the evaluation of heterogeneous clinical data, such as imaging exams, biochemical tests and the patient's clinical history. The lack of interoperability between Health Information Systems (HIS) does not allow the physicians to acquire all the necessary data for the diagnostic process. In this paper, a semantically-aided architecture is proposed for a web-based monitoring system for carotid atherosclerosis that is able to gather and unify heterogeneous data with the use of an ontology and to create a common interface for data access enhancing the interoperability of HIS. The architecture is based on an application ontology of carotid atherosclerosis that is used to (a) integrate heterogeneous data sources on the basis of semantic representation and ontological reasoning and (b) access the critical information using SPARQL query rewriting and ontology-based data access services. The architecture was tested over a carotid atherosclerosis dataset consisting of the imaging exams and the clinical profile of 233 patients, using a set of complex queries, constructed by the physicians. The proposed architecture was evaluated with respect to the complexity of the queries that the physicians could make and the retrieval speed. The proposed architecture gave promising results in terms of interoperability, data integration of heterogeneous sources with an ontological way and expanded capabilities of query and retrieval in HIS.

A novel computerized tool to stratify risk in carotid atherosclerosis using kinematic features of the arterial wall.

Valid characterization of carotid atherosclerosis (CA) is a crucial public health issue, which would limit the major risks held by CA for both patient safety and state economies. This paper investigated the unexplored potential of kinematic features in assisting the diagnostic decision for CA in the framework of a computer-aided diagnosis (CAD) tool. To this end, 15 CAD schemes were designed and were fed with a wide variety of kinematic features of the atherosclerotic plaque and the arterial wall adjacent to the plaque for 56 patients from two different hospitals. The CAD schemes were benchmarked in terms of their ability to discriminate between symptomatic and asymptomatic patients and the combination of the Fisher discriminant ratio, as a feature-selection strategy, and support vector machines, in the classification module, was revealed as the optimal motion-based CAD tool. The particular CAD tool was evaluated with several cross-validation strategies and yielded higher than 88% classification accuracy; the texture-based CAD performance in the same dataset was 80%. The incorporation of kinematic features of the arterial wall in CAD seems to have a particularly favorable impact on the performance of image-data-driven diagnosis for CA, which remains to be further elucidated in future prospective studies on large datasets.

Robust carotid artery recognition in longitudinal B-mode ultrasound images.

Automatic segmentation of the arterial lumen from ultrasound images is an important task in clinical diagnosis. Carotid artery recognition, the first task in lumen segmentation, should be performed in a fully automated, fast, and reliable way to further facilitate the low-level task of arterial delineation. In this paper, a user-independent, real-time algorithm is introduced for carotid artery localization in longitudinal B-mode ultrasound images. The proposed technique acts directly on the raw image, and exploits basic statistics along with anatomical knowledge. The method's evaluation and parameter value optimization were performed on a threefold cross validation basis. In addition, the introduced algorithm was systematically compared with another algorithm for common carotid artery recognition in B-mode scans, separately for multi-frame and single-frame data. The data sets used included 2,149 images from 100 subjects taken from three different institutions and covering a wide range of possible lumen and surrounding tissue representations. Using the optimized values, the carotid artery was recognized in all the processed images in both multi-frame and single-frame data. Thus, the introduced technique will further reinforce automatic segmentation in longitudinal B-mode ultrasound images.

CAROTID - a web-based platform for optimal personalized management of atherosclerotic patients.

Carotid atherosclerosis is the main cause of fatal cerebral ischemic events, thereby posing a major burden for public health and state economies. We propose a web-based platform named CAROTID to address the need for optimal management of patients with carotid atherosclerosis in a twofold sense: (a) objective selection of patients who need carotid-revascularization (i.e., high-risk patients), using a multifaceted description of the disease consisting of ultrasound imaging, biochemical and clinical markers, and (b) effective storage and retrieval of patient data to facilitate frequent follow-ups and direct comparisons with related cases. These two services are achieved by two interconnected modules, namely the computer-aided diagnosis (CAD) tool and the intelligent archival system, in a unified, remotely accessible system. We present the design of the platform and we describe three main usage scenarios to demonstrate the CAROTID utilization in clinical practice. Additionally, the platform was evaluated in a real clinical environment in terms of CAD performance, end-user satisfaction and time spent on different functionalities. CAROTID classification of high- and low-risk cases was 87%; the corresponding stenosis-degree-based classification would have been 61%. Questionnaire-based user satisfaction showed encouraging results in terms of ease-of-use, clinical usefulness and patient data protection. Times for different CAROTID functionalities were generally short; as an example, the time spent for generating the diagnostic decision was 5min in case of 4-s ultrasound video. Large datasets and future evaluation sessions in multiple medical institutions are still necessary to reveal with confidence the full potential of the platform.

Long-term clinical outcomes after percutaneous coronary intervention for chronic total occlusions.

Optimal treatment of chronic total occlusions (CTOs) remains one of the major challenges in interventional cardiology. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect percutaneous coronary intervention (PCI) success and long-term outcomes, in large multicenter cohorts as well as smaller patient groups. As opposed to patient-centered factors, technical factors can be managed and as a result, a lot of research aims at improving stent technology and imaging guidance, toward enhancing PCI efficiency, in regards to patient safety.

Toward novel noninvasive and low-cost markers for predicting strokes in asymptomatic carotid atherosclerosis: the role of ultrasound image analysis.

Stroke is a serious and frequent cerebrovascular disease with an enormous socioeconomic burden worldwide. Stroke prevention includes treatment of carotid atherosclerosis, the most common underlying cause of stroke, according to a specific diagnostic algorithm. However, this diagnostic algorithm has proved insufficient for a large number of mostly asymptomatic subjects, which poses a significant research challenge of identifying novel personalized risk markers for the disease. This paper illustrates the potential of carotid ultrasound image analysis toward this direction, with ultrasound imaging being a low-cost and noninvasive imaging modality and ultrasound-image-based features revealing valuable information on plaque composition and stability. A concise report of state-of-the-art studies in the field is provided and a perspective for clinical scenario for optimal management of atherosclerotic patients is described. Challenges and necessary future steps toward the realization of this scenario are discussed in an attempt to urge and orient future research, and mainly include systematic applications to sufficiently large patient samples, appropriately designed longitudinal studies, confirmation with histological results, and clinical trials.

Comparison of block matching and differential methods for motion analysis of the carotid artery wall from ultrasound images.

Motion of the carotid artery wall is important for the quantification of arterial elasticity and contractility and can be estimated with a number of techniques. In this paper, a framework for quantitative evaluation of motion analysis techniques from B-mode ultrasound images is introduced. Six synthetic sequences were produced using 1) a real image corrupted by Gaussian and speckle noise of 25 and 15 dB, and 2) the ultrasound simulation package Field II. In both cases, a mathematical model was used, which simulated the motion of the arterial wall layers and the surrounding tissue, in the radial and longitudinal directions. The performance of four techniques, namely optical flow (OF (HS)), weighted least-squares optical flow (OF (LK(WLS))), block matching (BM), and affine block motion model (ABMM), was investigated in the context of this framework. The average warping indices were lowest for OF (LK(WLS)) (1.75 pixels), slightly higher for ABMM (2.01 pixels), and highest for BM (6.57 pixels) and OF (HS) (11.57 pixels). Due to its superior performance, OF (LK(WLS)) was used to quantify motion of selected regions of the arterial wall in real ultrasound image sequences of the carotid artery. Preliminary results indicate that OF (LK(WLS)) is promising, because it efficiently quantified radial, longitudinal, and shear strains in healthy adults and diseased subjects.

Comparison of multiresolution features for texture classification of carotid atherosclerosis from B-mode ultrasound.

In this paper, a multiresolution approach is suggested for texture classification of atherosclerotic tissue from B-mode ultrasound. Four decomposition schemes, namely, the discrete wavelet transform, the stationary wavelet transform, wavelet packets (WP), and Gabor transform (GT), as well as several basis functions, were investigated in terms of their ability to discriminate between symptomatic and asymptomatic cases. The mean and standard deviation of the detail subimages produced for each decomposition scheme were used as texture features. Feature selection included 1) ranking the features in terms of their divergence values and 2) appropriately thresholding by a nonlinear correlation coefficient. The selected features were subsequently input into two classifiers using support vector machines (SVM) and probabilistic neural networks. WP analysis and the coiflet 1 produced the highest overall classification performance (90% for diastole and 75% for systole) using SVM. This might reflect WP's ability to reveal differences in different frequency bands, and therefore, characterize efficiently the atheromatous tissue. An interesting finding was that the dominant texture features exhibited horizontal directionality, suggesting that texture analysis may be affected by biomechanical factors (plaque strains).

Affine optical flow combined with multiscale image analysis for motion estimation of the arterial wall from B-mode ultrasound.

This paper investigated the performance of affine optical flow (AFOF) in motion tracking of the arterial wall from B-mode ultrasound images and the effect of its combination with multiscale image analysis on the accuracy of the process. Multiscale AFOF (MAFOF) exploits the information obtained with AFOF from the approximation sub-images at different spatial resolution levels of the images, obtained using a 2D discrete wavelet transform. Both AFOF and MAFOF were evaluated through their application to synthetic image sequences of the common carotid artery. Multiscale image analysis increased the accuracy in motion tracking, with MAFOF yielding average displacement error reductions of 9% with respect to AFOF. The methods were also effectively applied to real ultrasound image sequences of the carotid artery. The results showed that MAFOF could be considered as a reliable estimator for arterial wall motion from B-mode ultrasound images.