Multimodality carotid plaque tissue characterization and classification in the artificial intelligence paradigm: a narrative review for stroke application

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in the United States of America and globally. Carotid arterial plaque, a cause and also a marker of such CVD, can be detected by various non-invasive imaging modalities such as magnetic resonance imaging (MRI), computer tomography (CT), and ultrasound (US). Characterization and classification of carotid plaque-type in these imaging modalities, especially into symptomatic and asymptomatic plaque, helps in the planning of carotid endarterectomy or stenting. It can be challenging to characterize plaque components due to (I) partial volume effect in magnetic resonance imaging (MRI) or (II) varying Hausdorff values in plaque regions in CT, and (III) attenuation of echoes reflected by the plaque during US causing acoustic shadowing. Artificial intelligence (AI) methods have become an indispensable part of healthcare and their applications to the non-invasive imaging technologies such as MRI, CT, and the US. In this narrative review, three main types of AI models (machine learning, deep learning, and transfer learning) are analyzed when applied to MRI, CT, and the US. A link between carotid plaque characteristics and the risk of coronary artery disease is presented. With regard to characterization, we review tools and techniques that use AI models to distinguish carotid plaque types based on signal processing and feature strengths. We conclude that AI-based solutions offer an accurate and robust path for tissue characterization and classification for carotid artery plaque imaging in all three imaging modalities. Due to cost, user-friendliness, and clinical effectiveness, AI in the US has dominated the most

Novel ultrasound features for the identification of the vulnerable carotid plaque

Background: The identification of the vulnerable carotid plaque is of paramount importance in order to prevent the significant stroke-related mortality and morbidity. Currently the clinical decision-making around this condition is based on the traditional ultrasound evaluation of the degree of stenosis. However, there is emerging evidence supporting that this is not sufficient for all patients. Aim of this thesis: The evaluation of novel carotid plaque features for the characterisation of plaque composition, volume and motion using 2 and 3 dimensional ultrasound technology. The ultimate goal is to identify novel sensitive imaging markers for carotid plaque characterisation and stroke-risk stratification. Methods: The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) Study was a large prospective multicentre trial that was recently completed. A post-hoc analysis of the sonographic and clinical data from this study was performed in order to evaluate the effectiveness of novel ultrasound texture features, such as second order statics, on stroke-risk prediction. In addition, the change of specific texture features and degree of stenosis during the ACSRS follow-up time (8 years) and their importance for stroke prediction was evaluated. In order to assess the potential of 3D ultrasound carotid imaging we also developed a special methodology using a 3D broadband, linear array probe and the Q-lab software. This methodology was then applied in a clinical, cross-sectional study of patients with symptomatic and asymptomatic carotid disease. Finally we developed a carotid plaque motion analysis methodology that we tested on a feasibility study. Results: The post-hoc analysis of more than 1, 000 patients from the ACSRS database showed that there are novel ultrasound features of plaque homogeneity that can contribute to plaque characterisation and improve stroke-risk prediction. Similarly our results suggest that the change of degree of stenosis or plaque’s composition through time might have significant predictive value when combined with the above novel features. The study in 3D ultrasound prospectively assessed more than 80 people with symptomatic and asymptomatic carotid disease with both 2 and 3D carotid ultrasound without, though, revealing any significant benefit from the use of 3D imaging in terms of stroke-risk prediction. Finally, our feasibility study on plaque motion analysis showed that it is possible to objectively characterise plaque motion, using ultrasound and dedicated software without complicated reconstructions. Conclusion: The use of novel 2D ultrasound texture features in combination with traditional ones can improve the stroke-risk stratification. 3D ultrasound is a promising new approach, however, the current technology does not appear to offer a significant benefit in comparison to cheaper traditional 2D ultrasound for carotid plaque evaluation. Further research is warranted on this issue.Open Acces

Echolucency of carotid plaques correlates with plaque cellularity

AbstractObjective: to analyse the relationship between carotid plaque echolucency and cellularity. Methods: carotid plaques (14 symptomatic and 16 asymptomatic) were snap frozen after endarterectomy and defined on the basis of their grey-scale-median (GSM), obtained from pre-operative high-definition ultrasonography, as either echolucent (<32) or echogenic (≥32). DNA and total soluble protein were determined to assess cellularity. Results: after correcting for wet weight, symptomatic plaques had significantly more DNA (0.400 ± 0.07 vs 0.335 ± 0.07 mg/g; p = 0.03) and soluble protein (34.1 ± 6.6 vs 29.7 ± 3.4 mg/g; p = 0.03) than asymptomatic plaques. Predominantly echolucent (Grey-Weale classification) plaques had more DNA (0.404 ± 0.06 vs 0.332 ± 0.08 mg/g; p = 0.03) than echogenic plaques. Plaques with GSM < 32 also had more DNA (0.386 ± 0.08 vs 0.319 ± 0.06 mg/g; p = 0.04) and soluble protein (34.7 ± 7.3 vs 29.6 ± 4.2 mg/g; p = 0.03) than those with GSM ≥ 32. Inverse relations were found between GSM and plaque DNA (r = −0.47; p = 0.02) and soluble protein (r = −0.45; p = 0.02) as well as between age and DNA (r = 0.39; p = 0.04) and soluble protein (r = −0.50; p = 0.003). Conclusions: echolucency of carotid plaques as assessed by ultrasonography reflects plaque cellularity. This observation support the notion that ultrasonography can be used to identify high-risk plaques and evaluate effect of interventions on plaque structure.Eur J Vasc Endovasc Surg 26, 32-38 (2003

Carotid plaque morphology: A review

The recent North American Symptomatic Carotid Endarterectomy Trial has answered fairly conclusively the questions concerning the optimal management of patients with symptoms who have a > 70% stenosis of the internal carotid artery. It has also had the effect of refocusing attention on carotid pathology. The main question still to be answered is whether surgical management is the optimum treatment for other groups of patients with carotid disease. From various studies done on the natural history of carotid plaques it is apparent that there are subgroups who may benefit from surgery, namely those who will progress to stroke if not treated. The problem comes in identifying these subgroups by the factors which cause them to progress. This paper aims to review the role that plaque morphology has in the development of symptoms and whether it should be included with degree of stenosis in assessing the risk of a carotid plaque. The non-invasive assessment of plaque morphology is also reviewed. The evidence from this review does not support the use of plaque morphology as a discriminating factor for carotid endarterectomy at present

Multimarker approach in discriminating patients with symptomatic and asymptomatic atherosclerotic carotid artery stenosis

BACKGROUND AND PURPOSE: Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS). METHODS: Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization. RESULTS: CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively). CONCLUSIONS: In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA(2) may transiently indicate S transformation of the carotid atherosclerotic plaque

The identification of the vulnerable carotid plaque and haemodynamic compromise of the brain in carotid artery stenosis

Introduction: Carotid stenosis plays a large role in the aetiology of ischaemic stroke. The main mechanism of carotid stenosis causing stroke is the forming of thrombus and consequently embolus formation. Another mechanism is the compromise in haemodynamics: reduced blood flow distal from the stenosis causing hypoperfusion of the brain. This work investigates the current prevalence of carotid stenosis in ischaemic stroke. It also explores the role of transcranial Doppler (TCD) and brain perfusion imaging with magnetic resonance imaging in patients with carotid stenosis. Methods: The current prevalence of carotid stenosis was assessed in a comprehensive Central London hyper-acute stroke unit and a systematic review with meta-regression analysis was conducted on the prevalence of carotid stenosis. Patient individual risk factors and morphological characteristics of the carotid plaque were associated with the presence of micro-embolic signals on TCD. The perfusion of the brain was assessed in patients with carotid stenosis and those who underwent carotid endarterectomy (CEA). Results: The prevalence of carotid stenosis 350% in the local stroke unit was 19.0%, including 7.9% with symptomatic stenosis. The pooled prevalence estimate of carotid stenosis, described in 37 studies in the literature, was 16.0% and has not declined over time. Intraplaque haemorrhage was associated with a higher risk of future stroke by detection of micro-embolic signals on TCD. Haemodynamic factors played a great role in stroke, especially in patients with stenosis 370%. Cerebral perfusion improved significantly in patients who underwent CEA, especially in those who initially had 370% stenosis. Conclusion: Morphology of the plaque, more than the degree of stenosis, is an important predictive feature of the unstable carotid plaque, whilst the degree of stenosis is more relevant to the hypoperfused brain. There is evidence for a synergic role of embolism and haemodynamic compromise as a mechanism of ischaemic stroke in carotid stenosis

Computer aided diagnosis of coronary artery disease, myocardial infarction and carotid atherosclerosis using ultrasound images: a review

The diagnosis of Coronary Artery Disease (CAD), Myocardial Infarction (MI) and carotid atherosclerosis is of paramount importance, as these cardiovascular diseases may cause medical complications and large number of death. Ultrasound (US) is a widely used imaging modality, as it captures moving images and image features correlate well with results obtained from other imaging methods. Furthermore, US does not use ionizing radiation and it is economical when compared to other imaging modalities. However, reading US images takes time and the relationship between image and tissue composition is complex. Therefore, the diagnostic accuracy depends on both time taken to read the images and experience of the screening practitioner. Computer support tools can reduce the inter-operator variability with lower subject specific expertise, when appropriate processing methods are used. In the current review, we analysed automatic detection methods for the diagnosis of CAD, MI and carotid atherosclerosis based on thoracic and Intravascular Ultrasound (IVUS). We found that IVUS is more often used than thoracic US for CAD. But for MI and carotid atherosclerosis IVUS is still in the experimental stage. Furthermore, thoracic US is more often used than IVUS for computer aided diagnosis systems

Uses of ultrasound in stroke prevention

Ultrasound methods are useful in stroke prevention in several ways. Measurement of carotid plaque burden, as either total plaque area (TPA) or total plaque volume (TPV) are strong predictors of cardiovascular risk: much stronger than intima-media thickness, which does not represent true atherosclerosis, but a biologically and genetically distinct phenotype. Measurement of plaque burden is also useful for the study of genetics, and of new risk factors such as toxic products of the intestinal microbiome. Carotid plaque burden is highly correlated with and as predictive of risk as coronary calcium scores, but is less costly and does not require radiation. Furthermore, because carotid plaques change in time over a period of months, they can be used for a new approach to vascular prevention: “Treating arteries instead of treating risk factors”. In high-risk patients with asymptomatic carotid stenosis (ACS), this approach, implemented in 2003 in our clinics, was associated with a \u3e80% reduction of stroke and myocardial infarction over 2 years. “Treating arteries without measuring plaque would be like treating hypertension without measuring blood pressure”. Ultrasound methods can also be used to assess plaque vulnerability, by detecting echolucency, ulceration and plaque inhomogeneity on assessment of plaque texture. Transcranial Doppler (TCD) embolus detection is useful for risk stratification in patients with ACS; patients with two or more microemboli in an hour of monitoring have a 1-year risk of 15.6%, vs. 1% without microemboli, so this very clearly distinguishes which patients with ACS could benefit from intervention. TCD saline studies are more sensitive than trans-esophageal echocardiography for detection of patent foramen ovale, and more predictive of recurrent stroke. These methods should be more widely used, to reduce the increasing burden of stroke in our aging populations