Inflammation within Carotid Atherosclerotic Plaque: Assessment with Late-Phase Contrast-enhanced US

Abstract

Purpose:To determine if the number of nontargeted microbubbles retained in human carotid plaque is suffi cient to be detected with ultrasonography (US). Materials and Methods:The study protocol was approved by the local research ethics committee. Informed consent was obtained. A total of 37 subjects with carotid atherosclerosis (mean age, 69.9 years; age range, 49-86 years), of whom 27 (73%) were men (mean age, 69.7 years; age range, 58-86 years) and 10 (27%) were women (mean age, 70.3 years; age range, 49-86 years), were studied between December 2008 and May 2009 with late-phase (LP) contrast material-enhanced US by using fl ash imaging with a nonlinear mode at an intermediate mechanical index of 0.34 6 minutes after bolus contrast agent injection. Plaques were defi ned as symptomatic if symptoms consistent with stroke, transient ischemic attack, or amaurosis fugax had occurred in the neurovascular territory of the plaque studied within 12 months prior to entry into the study. Plaques were defi ned as asymptomatic if no such events had ever occurred within the neurovascular territory. Raw linear data were used to quantify echogenicity of the plaque, which was normalized to lumen echogenicity. Gray-scale median score was also calculated. Results:Of the 37 subjects, 16 (43%) had symptomatic plaques and 21 (57%) had asymptomatic plaques. All examinations yielded evaluable LP contrast-enhanced US data. Normalized LP plaque echogenicity was greater in the symptomatic group (0.39; 95% confi dence interval: 2 0.11, 0.89) than in the asymptomatic group (0.69; 95% confi dence interval: 2 1.04, 2 0.34) ( P = .0005). There was a moderate ( r = 2 0.44, P = .016) inverse correlation between normalized LP plaque echogenicity and gray-scale median score. Conclusion:By quantifying microbubble retention within the carotid plaque, LP contrast-enhanced US depicts clear differences between groups of subjects with plaque ipsilateral to symptoms and asymptomatic plaques. This technique has promise as a tissue-specifi c marker of infl ammation and a potential role in the risk stratifi cation of atherosclerotic carotid stenosis.q RSNA, 2010

Late-Phase Contrast-Enhanced Ultrasound Reflects Biological Features of Instability in Human Carotid Atherosclerosis

“…LP-CEUS signal from a number of these patients has previously been reported. 3 Carotid plaques from 16 (52%) patients were symptomatic if stroke, transient ischemic attack, or amaurosis fugax occurred in the index plaque neurovascular territory within 12 months of enrollment. Median time from symptoms to LP-CEUS was 21.0 days.…”

“…2 Recently, late-phase-(LP-) CEUS at 6 minutes postcontrast has distinguished human symptomatic from asymptomatic carotid plaques in vivo. 3 In this study, our primary hypothesis was that LP-CEUS would reflect inflammation and angiogenesis determined by immunohistochemistry. We further wanted to explore whether LP-CEUS could offer information about cytokine, chemokine, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase levels.…”

Advances in imaging vascular inflammation

“…Late-phase contrast-enhanced ultrasound using microbubbles can assess inflammation within carotid plaques [60]. Microbubbles are taken up by phagocytic cells and remain acoustically active for around 30 min.…”

“…Imaged with FDG PET, implanted rats displayed higher levels of aortic FDG uptake compared with controls. Histological analysis • Quantify arterial inflammation [60] and neovascularization • Differentiate symptomatic and asymptomatic plaques [61] • Identify areas of active leukocyte recruitment [62] Computed tomography…”

Current Strategies and Possible Perspectives of Ultrasonic Risk Stratification of Ischemic Stroke in Internal Carotid Artery Disease

“…However, it is still unclear whether there is any clinical indication for the imaging of atherosclerosis. However, the recent observation that microbubbles can be detected approximately 6 minutes after application (late phase CEUS) significantly more often in symptomatic plaques than in asymptomatic plaques may serve as a marker of inflammation and therefore "active" atherosclerosis in this context [62].…”