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.

Hypothesis of “stroke-stop” formula: a tool for risk index determination in development of acute cerebrovascular disease in asymptomatic individuals with carotid stenosis

“…Specific vascular markers may serve as one of the criteria for assessing inflammation and destabilization of atherosclerotic plaque. In scientific journals, many articles on the comparison of different vascular markers were published [18,19]. However, Lp-PLA2 is currently considered an independent biomarker for stroke, as well as coronary artery disease and peripheral arterial occlusive disease [21].…”

“…Therefore, the criteria for selecting patients for surgical prevention of acute cerebrovascular disease among asymptomatic individuals with carotid stenosis are broadly discussed nowadays [13,14]. There have been several studies, where in addition to atherosclerotic ICA stenosis, the morphological structure of the atherosclerotic plaque was taken into consideration [15][16][17][18]. In recent years, researchers have widely investigated vascular inflammatory markers as well as the relationship between their concentration and the risk of developing atherosclerotic complications [19].…”

Diagnostic utility of superb microvascular imaging in depiction of corkscrew collaterals in Buerger's disease

“…Vascular applications of SMI mainly focused on characterization of carotid plaques by assessing neovascularization 16 . This could potentially identify vulnerable plaques and have important implications in stroke management 17 . Additional vascular studies of SMI focused on endo‐leaks after aortic grafting, visualization of hepatic artery after liver transplant, cardiac imaging in fetuses, and assessment of intracranial vasculature in neonatal transcranial ultrasonography 18‐21 .…”