Advanced ultrasound Methods in assessment of carotid plaque instability: A prospective multimodal study

Abstract Background: A significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young’s modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments. Methods: Thirty symptomatic and 30 asymptomatic patients >18 years, with >50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this on-going project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18F-FDG). Contrast enhanced ultrasound will be analyzed semi-quantitatively (5-levels of visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured. Discussion: This multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1-year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

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Advanced ultrasound Methods in assessment of carotid plaque instability: A prospective multimodal study

10.21203/rs.2.9292/v3 ◽

2019 ◽

Author(s):

Mahtab Zamani ◽

Karolina Skagen ◽

Helge Scott ◽

David Russell ◽

Mona Skjelland

Keyword(s):

Carotid Artery ◽

Stroke Risk ◽

Significant Proportion ◽

Contrast Enhanced Ultrasound ◽

Carotid Artery Plaque ◽

Plaque Instability ◽

Carotid Mri ◽

Contrast Enhanced ◽

Risk Of Rupture ◽

18F Fdg

Abstract Background: A significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young’s modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments. Methods: Forty five symptomatic and 45 asymptomatic patients >18 years, with >50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this on-going project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18F-FDG). Contrast enhanced ultrasound will be analyzed semi-quantitatively (5-levels visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured. Discussion: This multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1-year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

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Advanced ultrasound Methods in assessment of carotid plaque instability: A prospective multimodal study

10.21203/rs.2.9292/v4 ◽

2020 ◽

Author(s):

Mahtab Zamani ◽

Karolina Skagen ◽

Helge Scott ◽

David Russell ◽

Mona Skjelland

Keyword(s):

Carotid Artery ◽

Stroke Risk ◽

Significant Proportion ◽

Contrast Enhanced Ultrasound ◽

Carotid Artery Plaque ◽

Plaque Instability ◽

Carotid Mri ◽

Contrast Enhanced ◽

Risk Of Rupture ◽

18F Fdg

Abstract Background: A significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young’s modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments. Methods: Forty five symptomatic and 45 asymptomatic patients >18 years, with >50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this on-going project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18F-FDG). Contrast enhanced ultrasound will be analyzed semi-quantitatively (5-levels visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured. Discussion: This multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1-year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

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Advanced ultrasound Methods in assessment of carotid plaque instability: A prospective multimodal study

10.21203/rs.2.9292/v2 ◽

2019 ◽

Author(s):

Mahtab Zamani ◽

Karolina Skagen ◽

Helge Scott ◽

David Russell ◽

Mona Skjelland

Keyword(s):

Carotid Artery ◽

Stroke Risk ◽

Significant Proportion ◽

Contrast Enhanced Ultrasound ◽

Carotid Artery Plaque ◽

Plaque Instability ◽

Carotid Mri ◽

Contrast Enhanced ◽

Risk Of Rupture ◽

18F Fdg

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Contrast-enhanced ultrasound perfusion patterns and serum lipid signatures of vulnerable carotid artery plaque in predicting stroke: A cohort study of carotid stenosis in Chinese patients

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-190804 ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Yunqian Huang ◽

Qi Liu ◽

Junmei Xu ◽

Wenqian Zhu ◽

Jianwei Jiang ◽

...

Keyword(s):

Cohort Study ◽

Carotid Artery ◽

Carotid Stenosis ◽

Serum Lipid ◽

Chinese Patients ◽

Contrast Enhanced Ultrasound ◽

Carotid Artery Plaque ◽

Contrast Enhanced

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Inter-reader agreement of 18F-FDG PET/CT for the quantification of carotid artery plaque inflammation

10.1101/807420 ◽

2019 ◽

Author(s):

Kjersti Johnsrud ◽

Therese Seierstad ◽

David Russell ◽

Mona-Elisabeth Revheim

Keyword(s):

Carotid Artery ◽

Fdg Pet ◽

Stroke Risk ◽

Significant Proportion ◽

Background Correction ◽

Carotid Artery Plaque ◽

Pet Ct ◽

Significant Difference ◽

Plaque Inflammation ◽

Fdg Pet Ct

AbstractBackgroundA significant proportion of ischemic strokes are caused by emboli from unstable atherosclerotic carotid artery plaques with inflammation being a key feature of plaque instability and stroke risk. Positron emission tomography (PET) depicting the uptake of 2-deoxy-2-(18F)-fluoro-D-glucose (18F-FDG) in carotid artery plaques is a promising technique to quantify plaque inflammation. A consensus on the methodology for plaque localization and quantification of inflammation by 18F-FDG PET/computed tomography (CT) in atherosclerosis has not been established. High inter-reader agreement is essential if 18F-FDG PET/CT is to be used as a clinical tool for the assessment of unstable plaques and stroke risk. The aim of our study was to assess the inter-reader variability of different methods for quantification of 18F-FDG uptake in carotid atherosclerotic plaques with a separate CT angiography (CTA) providing anatomical guidance.Methods and resultsForty-three patients with carotid artery stenosis ≥70% underwent 18F-FDG PET/CT. Two independent readers separately delineated the plaque in all axial PET slices containing the atherosclerotic plaque and the maximum standardized uptake value (SUVmax) from each slice was measured. Uptake values with and without background correction were calculated. Intraclass correlation coefficients were highest for uncorrected uptake values (0.97-0.98) followed by those background corrected by subtraction (0.89-0.94) and lowest for those background corrected by division (0.74-0.79). There was a significant difference between the two readers definition of plaque extension, but this did not affect the inter-reader agreement of the uptake parameters.ConclusionsQuantification methods without background correction have the highest inter-reader agreement for 18F-FDG PET of carotid artery plaque inflammation. The use of the single highest uptake value (max SUVmax) from the plaque will facilitate the method’s clinical utility in stroke prevention.

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Contrast-enhanced ultrasound imaging of the vasa vasorum of carotid artery plaque

World Journal of Radiology ◽

10.4329/wjr.v7.i6.131 ◽

2015 ◽

Vol 7 (6) ◽

pp. 131 ◽

Cited By ~ 3

Author(s):

Ze-Zhou Song

Keyword(s):

Carotid Artery ◽

Ultrasound Imaging ◽

Vasa Vasorum ◽

Contrast Enhanced Ultrasound ◽

Carotid Artery Plaque ◽

Contrast Enhanced

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Abstract 11733: Assessment of Carotid Plaque Neovascularization Using Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging is Useful for Risk Stratification in Patients With Coronary Artery Disease

Circulation ◽

10.1161/circ.130.suppl_2.11733 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Jun Nakamura ◽

Takamitsu Nakamura ◽

Juntaro Deyama ◽

Daisuke Fujioka ◽

Ken-ichi Kawabata ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Quantitative Analysis ◽

Carotid Artery ◽

Carotid Plaque ◽

Contrast Enhanced Ultrasound ◽

Baseline Model ◽

Contrast Enhanced ◽

Traditional Risk Factors ◽

Artery Disease

Introduction: Extensive neovascularization in atherosclerotic plaque has been shown to be associated with plaque progression and instability, leading to atherosclerotic cardiovascular events. Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization. Hypothesis: Assessment of intra-plaque neovascularization of the carotid artery using quantitative analysis of CEUS provides prognostic information in patients with coronary artery disease (CAD). Methods: This study included 206 patients with stable CAD and with carotid intima-media thickness (IMT) > 1.1 mm. They underwent a CEUS examination of the carotid artery and were followed-up prospectively for < 38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction [MI], unstable angina pectoris [uAP] requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque after the intravenous injection of contrast material was quantified by calculating the increase in mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. Results: During the follow-up period (3 - 38 months, mean 22.8 ± 11.8 months), 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazards analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.52; 95% CI, 1.20 - 1.94; p = 0.001). The addition of plaque enhanced intensity had a significant incremental effect on the area under the ROC curve (AUC) generated using baseline model of traditional risk factors (AUC: baseline model 0.69 vs. baseline model + plaque enhanced intensity 0.78, p = 0.03). The addition of the plaque enhanced intensity to the baseline risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58, p = 0.003; and IDI 0.078, p = 0.03). Conclusions: The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.

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Contrast Enhanced Ultrasound: Visualization of Far Field and Classification of Plaque in the Extracranial Carotid Arteries

Journal for Vascular Ultrasound ◽

10.1177/1544316718783739 ◽

2018 ◽

Vol 42 (3) ◽

pp. 109-115 ◽

Cited By ~ 1

Author(s):

Paige L. Rowland ◽

Michelle Colpitts ◽

Angela Malone ◽

Munis Raza ◽

Lenora L. Eberhart ◽

...

Keyword(s):

Image Quality ◽

Carotid Artery ◽

Carotid Arteries ◽

Carotid Artery Disease ◽

Plaque Morphology ◽

Far Field ◽

Contrast Enhanced Ultrasound ◽

Contrast Imaging ◽

Contrast Enhanced ◽

Artery Disease

Ultrasound stratification for the degree of carotid artery disease based solely on lumen reduction has poorly predicted patient outcomes. This pilot study focused on patients with moderate carotid artery stenosis. Our purpose was to use contrast imaging with ultrasound to improve carotid field. A total of 10 patients diagnosed with moderate carotid artery stenosis were rescanned with an administration of a contrast imaging agent. Two-dimensional (2D) imaging, color, and Doppler were utilized to scan the patients. The 20 carotid arteries were blindly read by 2 experienced physicians. Visualization of far field, quality of Doppler envelope, plaque morphology, and overall image quality were semi-quantifiably assessed. With the use of a contrast imaging agent, there was a reduction in interphysician interpretation variability. The Kappa coefficient yielded an increase in agreement for postcontrast imaging in the majority of variables. The Doppler envelope showed improvement from precontrast (0.06) to postcontrast (0.63). The visualization of the far fields demonstrated a significant increase in agreement (0.77, 0.71, and 0.67) postcontrast. Plaque morphology demonstrated enhancement in characterization with contrast (–0.09 to 0.66). In this study, contrast-enhanced ultrasound (CEUS) was found to increase overall image quality. Improved interpretation can enhance risk stratification and with further exploration could be used to guide treatment plans for patients with asymptomatic moderate carotid artery disease.

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Clinical and Contrast-Enhanced Ultrasound Echography Outcomes in Psoriatic Arthritis Patients after One Year of Continuous Therapy with Anti-TNF Drugs

ISRN Dermatology ◽

10.1155/2014/932721 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Claudio Bonifati ◽

Fulvia Elia ◽

Dario Graceffa ◽

Fabrizio Ceralli ◽

Elisa Maiani ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Significant Proportion ◽

Joint Inflammation ◽

Joint Involvement ◽

Contrast Enhanced Ultrasound ◽

Continuous Therapy ◽

Clinical Variables ◽

Contrast Enhanced ◽

Before And After ◽

One Year

Background. We wanted to verify retrospectively the proportion of patients with psoriatic arthritis who were in remission after 1 year of continuous therapy with either etanercept or adalimumab. Remission was defined as the absence of both clinical and contrast-enhanced ultrasound (CEUS) findings suggestive of joint inflammation. Patients and Methods. The data of twenty-five patients with psoriatic arthritis were available for the clinical and CEUS evaluations before and after 1 year of continuous therapy with etanercept or adalimumab. The count of swollen (ACR66), tender (ACR68), and active inflamed joints (AJC) was used to measure the severity of joint involvement. PASI was used to score the severity of psoriasis. HAQ, DLQI, VAS pain, and VAS itching were administered to each patient before starting therapy and every 3 months, up to 1 year. Results. Eight (32%) out of twenty-five patients were in remission after 1 year of therapy with etanercept or adalimumab. A significant reduction of all clinical variables analysed was seen during the course of therapy. Conclusion. Although a significant proportion of patients achieved remission of arthritis after 1 year of effective anti-TNF therapy, the majority of them continued to have either clinical or CEUS findings suggestive of persistence of joint inflammation.

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Carotid artery vulnerable plaque model for cerebrovascular events by conventional ultrasound & contrast-enhanced ultrasound: A preliminary study

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211216 ◽

2021 ◽

pp. 1-13

Author(s):

Qin Wang ◽

Yunqian Huang ◽

Yuke Zhang ◽

Yuqun Wang ◽

Yanchun Xie ◽

...

Keyword(s):

High Risk ◽

Carotid Artery ◽

Vulnerable Plaque ◽

Cerebrovascular Event ◽

Contrast Enhanced Ultrasound ◽

Carotid Ultrasound ◽

Test Set ◽

Cerebrovascular Events ◽

Contrast Enhanced ◽

Conventional Ultrasound

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques plaque model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

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