Project

Back to overview

Clinical Use of Contrast-Enhanced Ultrasound (CEUS) for the Assessment of Vessel Wall Vascularization (Vasa Vasorum) and Inflammation in Carotid Atherosclerosis and Venous Thrombosis

Applicant Staub Daniel
Number 142419
Funding scheme Ambizione
Research institution Abteilung für Angiologie Medizinische Universitätsklinik A Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Cardiovascular Research
Start/End 01.10.2012 - 31.03.2015
Approved amount 270'882.00
Show all

All Disciplines (2)

Discipline
Clinical Cardiovascular Research
Internal Medicine

Keywords (8)

Vasa vasorum; Ultrasound; Atherosclerosis; Inflammation; Thrombosis; Contrast; carotid plaque; vascular event

Lay Summary (English)

Lead
Lay summary

Atherosclerosis is a chronic, systemic and progressive disease affecting different arterial blood vessels in the body. Atherosclerotic lesions silently progress from small plaques to severe stenosis and may remain asymptomatic for years. Unstable plaques and stenosis (also called vulnerable plaques), however, are prone to rupture leading to myocardial infarction, or stroke. The proliferation of the small arteries that are distributed to the outer and middle coats of the largerer blood vessels (vasa vasorum) and within the atherosclerotic plaques (neovascularization) are inherently linked with the atherosclerotic plaque development, plaque inflammation and vulnerability. By injecting ultrasound contrast agents (microbubbles) into the blood stream, it is possible to detect this microcirculation of the vessel wall and the neovascularization within the atherosclerotic plaque using a contrast-enhanced ultrasound (CEUS) imaging technique. Particularly, CEUS of the carotid artery has been introduced as a non-invasive technique to improve detection of carotid atherosclerosis and to evaluate the presence of carotid plaque neovascularization which has emerged as a new marker for plaque vulnerability. The project investigates the predictive value of the detection of carotid plaque neovascularization on CEUS imaging in patients with suspected coronary artery disease and with known asymptomatic carotid artery stenosis (no previous stroke) regarding the progression of the carotid atherosclerotic lesion and future vascular events including myocardial infarction, stroke or vascular intervention. We hypothesize that neovascularization within the carotid lesion at baseline will significantly be more pronounced in patients with progressive carotid lesions and in patients suffering future vascular events during follow-up. The project will support the concept that intraplaque neovascularization is associated with plaque instability and vulnerability and therefore, the use of CEUS may provide an additional non-invasive, simple, safe, and reliable imaging modality to risk stratify individuals. The identification of vulnerable and more progressive carotid lesions that are at increased risk of rupture by identification of intraplaque neovascularization is expected to improve the prediction of future vascular events and thus allow for better treatment selection. It will help the clinician to further risk stratify carotid stenosis. Particularly, it will help to identify unstable carotid stenosis that may already benefit from invasive therapy as carotid thromboendarterectomy and stenting, and may refrain patients from invasive therapy with stable stenosis.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in vascular medicine.
Kaspar Mathias, Partovi Sasan, Aschwanden Markus, Imfeld Stephan, Baldi Thomas, Uthoff Heiko, Staub Daniel (2015), Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in vascular medicine., in Swiss medical weekly, 145, 14047-14047.
Atherosclerotic plaque neovascularization and inflammation – is there a link?
Staub Daniel (2015), Atherosclerotic plaque neovascularization and inflammation – is there a link?, Vasa, Bern.
Quantitative dynamic contrast-enhanced ultrasound for the functional evaluation of the skeletal muscle microcirculation in systemic sclerosis.
Partovi Sasan, Kaspar Mathias, Aschwanden Markus, Robbin Mark R, Bilecen Deniz, Walker Ulrich A, Staub Daniel (2015), Quantitative dynamic contrast-enhanced ultrasound for the functional evaluation of the skeletal muscle microcirculation in systemic sclerosis., in Clinical hemorheology and microcirculation, Mar 10. [Epub ahead of print], 1.
[Contrast-enhanced ultrasound in vascular medicine: what is new?].
Kaspar M, Staub D (2014), [Contrast-enhanced ultrasound in vascular medicine: what is new?]., in Deutsche medizinische Wochenschrift (1946), 139(23), 1200-3.
Novel applications of contrast-enhanced ultrasound imaging in vascular medicine.
Staub Daniel, Partovi Sasan, Imfeld Stephan, Uthoff Heiko, Baldi Thomas, Aschwanden Markus, Jaeger Kurt (2013), Novel applications of contrast-enhanced ultrasound imaging in vascular medicine., in VASA. Zeitschrift für Gefässkrankheiten, 42(1), 17-31.
Assessment of cutaneous microcirculation in unaffected skin regions by transcutaneous oxygen saturation monitoring and Laser Doppler flowmetry in systemic sclerosis.
Broz Pavel, Aschwanden Markus, Partovi Sasan, Schulte Anja-Carina, Benz Daniela, Takes Martin, Walker Ulrich A, Bilecen Deniz, Jaeger Kurt A, Imfeld Stephan, Staub Daniel, Assessment of cutaneous microcirculation in unaffected skin regions by transcutaneous oxygen saturation monitoring and Laser Doppler flowmetry in systemic sclerosis., in Clinical hemorheology and microcirculation.

Collaboration

Group / person Country
Types of collaboration
Divsion of Hematology, Haemostasis Laboratory, University Hospital Basel, Prof.Tsakiris Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Department of Cardiology, Rush University, Chicago, Prof. Feinstein United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Department of Cardiology, Erasmus Medical Center, Rotterdam, Dr. Schinkel Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Cardiovascular molecular imaging research group, University Hospital Basel, PD Dr. Beat Kaufmann Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Cardiovascular Outcome and Processes, University Hospital Basel, Prof. Müller Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Bracco SA, Geneva Research Centre Switzerland (Europe)
- Industry/business/other use-inspired collaboration

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
26th Congress of EFSUMB Talk given at a conference New surrogate marker of plaque vulnerability: carotid plaque neovascularization on CEUS 28.05.2014 Tel Aviv, Israel Staub Daniel;
19th European symposium on ultrasound contrast imaging. Talk given at a conference Perivascular venous vascularization on contrast enhanced ultrasound (CEUS) is correlated with inflammation in patients with acute deep vein thrombosis. 23.01.2014 Rotterdam, Netherlands Staub Daniel;
3rd Munich Aortic and Carotid Conference Talk given at a conference CEUS to asses neovascularization of the carotid bifurcation 28.11.2013 München, Germany Staub Daniel;


Associated projects

Number Title Start Funding scheme
120997 Contrast enhanced ultrasound imaging of neovascularization in vulnerable carotid plaques 01.01.2008 Fellowships for prospective researchers

Abstract

Background: Injection of ultrasound contrast agents, in conjunction with contrast specific imaging techniques, is increasingly accepted in clinical use for diagnostic ultrasound imaging. As microbubbles contrast agents appear to be ideal pure intravascular tracers to enhance the vascular lumen and more important to assess the dynamic spatial and temporal heterogeneity of the microvasculature, contrast enhanced ultrasound (CEUS) provides a unique opportunity for new application especially in vascular imaging. CEUS of the carotid artery has been introduced as a non-invasive technique to improve detection of carotid atherosclerosis and evaluate the presence of plaque vascularity (vasa vasorum). As the proliferation of intraplaque and adventitial vasa vasorum (neovascularization) are inherently linked with the atherosclerotic plaque development, plaque inflammation and vulnerability, direct visualization of intraplaque neovascularization by CEUS has emerged as a new marker for plaque instability. Furthermore, CEUS provides not only direct in-vivo visualization of the vessel wall vascularization. Late phase CEUS has shown to detect plaque inflammation by visualizing untargeted microbubbles phagozytosed by monocytes. The inflammatory process of the vessel wall is not only involved in the atherosclerotic plaque development but also in the inflammatory process at the time of venous thrombosis and may promote destruction of venous valves, valvular reflux and subsequent development of post-thrombotic syndrome.Aim: It is the aim of this project to perform prospective studies with clinical questions and test the hypothesis that the use of CEUS to detect vessel wall vascularization and inflammation can improve the management of patients with atherosclerotic and thrombotic diseases. Methods: The study project 1 will prospectively evaluate the value of carotid atherosclerosis severity and plaque morphology including intraplaque neovascularization on standard carotid ultrasound and CEUS in 400 high risk patients with suspected coronary artery disease referred for radionuclide myocardial perfusion imaging to predict future vascular events. We hypothesize that patients with instable coronary artery disease and patients with future vascular events during a follow-up of 5 years have more pronounced intraplaque neovascularization on CEUS imaging at baseline. The study project 2 will prospectively evaluate the predictive value of carotid lesion morphology and severity including intraplaque neovascularization on standard carotid ultrasound and CEUS in 240 patients with asymptomatic more than 50% carotid stenosis. We hypothesize that neovascularization within the carotid lesion at baseline will significantly be more pronounced in patients with progressive carotid stenosis determined by repeated yearly carotid ultrasound studies over 5 years and in patients suffering future cerebrovascular and coronary events during follow-up. In patient scheduled for carotid endarterectomy we will investigate the feasibility of ex vivo assessment of vascular inflammation in carotid endarterectomy specimens using targeted microbubbles for molecular ultrasound imaging. In the study project 3, we will test the value of CEUS to detect venous perivascular vascularization and inflammation in 30 patients with acute deep vein thrombosis and 10 patients with superficial vein thrombosis. We hypothesize that venous perivascular vascularization and inflammation assessed by contrast agent enhancement will be significantly more pronounced in the perivascular tissue of the thrombotic popliteal vein than in the non affected contralateral popliteal vein and in 40 control volunteers, and will correlate with level of inflammatory markers, leg volume and the development of the post-thrombotic syndrome. We hypothesize that vascularization and inflammation on CEUS will decrease during the process of thrombus resolution from baseline to 6 months follow-up. Significance: In sum, the results of our study projects would support the concept that intraplaque neovascularization is associated with plaque instability and vulnerability and the use of CEUS imaging may provide an additional non-invasive adjunctive “window” to risk stratify individuals and carotid atherosclerotic lesions, particularly asymptomatic more than 50% stenosis. Furthermore, the results would not only provide new information on vessel wall vascularization and inflammation in atherosclotic disease but also during venous thrombotic disease. This will help to better understand the pathophysiological concept of venous thrombosis, thrombus resolution and subsequent development of post-thrombotic syndrome.
-