Daniel Staub

Vasa Vasorum and Plaque Neovascularization on Contrast-Enhanced Carotid Ultrasound Imaging Correlates With Cardiovascular Disease and Past Cardiovascular Events

Background and Purpose— Histological data associate proliferation of adventitial vasa vasorum and intraplaque neovascularization with vulnerable plaques represented by symptomatic vascular disease. In this observational study, the presence of carotid intraplaque neovascularization and adventitial vasa vasorum were correlated with the presence and occurrence of cardiovascular disease (CVD) and events (CVE). Methods— The contrast-enhanced carotid ultrasound examinations of 147 subjects (mean age 64±11 years, 61% male) were analyzed for the presence of intraluminal plaque, plaque neovascularization (Grade 1=absent; Grade 2=present), and degree of adventitial vasa vasorum (Grade 1=absent, Grade 2=present). These observations were correlated with preexisting cardiovascular risk factors, presence of CVD, and history of CVE (myocardial infarction and transient ischemic attack/stroke). Results— The presence of intraluminal carotid plaque was directly correlated to cardiovascular risk factors, CVD, and CVE (P<0.05). Adventitial vasa vasorum Grade 2 was associated with significant more subjects with CVD than vasa vasorum Grade 1 (73 versus 54%, P=0.029). Subjects with intraplaque neovascularization Grade 2 had significantly more often a history of CVE than subjects with intraplaque neovascularization Grade 1 (38 versus 20%, P=0.031). Multivariate logistic regression analysis revealed that presence of plaque was significantly associated with CVD (odds ratio 4.7, 95% CI 1.6 to 13.8) and intraplaque neovascularization grade 2 with CVE (odds ratio 4.0, 95% CI 1.3 to 12.6). Conclusion— The presence and degree of adventitial vasa vasorum and plaque neovascularization were directly associated with CVD and CVE in a retrospective study of 147 patients undergoing contrast-enhanced carotid ultrasound.

Contrast-Enhanced Ultrasound Imaging of the Vasa Vasorum: From Early Atherosclerosis to the Identification of Unstable Plaques

Proliferation of the adventitial vasa vasorum (VV) is inherently linked with early atherosclerotic plaque development and vulnerability. Recently, direct visualization of arterial VV and intraplaque neovascularization has emerged as a new surrogate marker for the early detection of atherosclerotic disease. This clinical review focuses on contrast-enhanced ultrasound (CEUS) as a noninvasive application for identifying and quantifying carotid and coronary artery VV and intraplaque neovascularization. These novel approaches could potentially impact the clinicians ability to identify individuals with premature cardiovascular disease who are at high risk. Once clinically validated, the uses of CEUS may provide a method to noninvasively monitor therapeutic interventions. In the future, the therapeutic use of CEUS may include ultrasound-directed, site-specific therapies using microbubbles as vehicles for drug and gene delivery systems. The combined applications for diagnosis and therapy provide unique opportunities for clinicians to image and direct therapy for individuals with vulnerable lesions.

Correlation of Carotid Artery Atherosclerotic Lesion Echogenicity and Severity at Standard US with Intraplaque Neovascularization Detected at Contrast-enhanced US

PURPOSE To correlate echogenicity and severity of atherosclerotic carotid artery lesions at standard ultrasonography (US) with the degree of intraplaque neovascularization at contrast material-enhanced (CE) US. MATERIALS AND METHODS This HIPAA-compliant study was approved by the local ethics committee, and all patients provided informed consent. A total of 175 patients (113 [65%] men, 62 [35%] women; mean age, 67 years ± 10 [standard deviation]) underwent standard and CE US of the carotid artery. Lesion echogenicity (class I to IV), degree of stenosis, and maximal lesion thickness were evaluated for each documented atherosclerotic lesion. The degree of intraplaque neovascularization at CE US was categorized as absent (grade 1), moderate (grade 2), or extensive (grade 3). Correlation of neovascularization with echogenicity, degree of stenosis, and maximal lesion thickness was made by using Spearman ρ and χ(2) test for trend. RESULTS In a total of 293 atherosclerotic lesions, echogenicity was inversely correlated with grade of intraplaque neovascularization (ρ = -0.199, P < .001). More echolucent lesions had a higher degree of neovascularization compared with more echogenic ones (P < .001). The degree of stenosis was significantly correlated with grade of intraplaque neovascularization (ρ = 0.157, P = .003). Lesions with higher degree of stenosis had higher grade of neovascularization (P = .008), and maximal lesion thickness increased with the grade of neovascularization (P < .001) and was significantly correlated with grade of neovascularization (ρ = 0.233, P < .001). CONCLUSION Neovascularization visualized with CE US correlates with lesion severity and with morphologic features of plaque instability, contributing to the concept that more vulnerable plaques are more likely to have a greater degree of neovascularization. Therefore, CE US may be a valuable tool for further risk stratification of echolucent atherosclerotic lesions and carotid artery stenosis of different degrees. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10101008/-/DC1.

Comparison of Carotid Arterial Resistive Indices With Intima-Media Thickness as Sonographic Markers of Atherosclerosis

Background and Purpose— The intima-media thickness (IMT) of the carotid artery is a (morphological) sonographic parameter that depends on the degree of atherosclerosis. In the renal arteries, the value of the (hemodynamic) resistive index (RI) is correlated with the severity of atherosclerosis. In contrast to the well-known IMT, no study has yet applied the carotid RI to estimate generalized atherosclerosis. Methods— The SMART atherosclerosis risk score was determined in 157 patients (94 men and 63 women; mean age 63 [range 19 to 80] years) with at least 1 vascular risk factor or a known vascular disease. Duplex sonography of the common carotid (CCA) and internal carotid artery (ICA) was then performed, with determination of IMT and RI. Results— The mean risk score of all patients was 8.8±3.5 (range 1 to 17), the mean IMT value in the CCA was 0.727±0.161 mm, the mean RI in CCA was 0.79±0.066, and the mean RI in ICA was 0.661±0.082. Highly significant correlations were found between the score and IMT CCA and the score and RI ICA (r =0.62, P <0.0001 and r =0.55, P <0.0001). The score–RI CCA correlation was much less marked (r =0.354, P <0.0001). The intraobserver and interobserver agreement was less for IMT than for RI CCA and ICA. The areas under the curve of the receiver operating curves to distinguish between low-risk and high-risk patients resulted in values of 0.86, 0.81, and 0.69 for IMT, RI ICA, and RI CCA, respectively. Conclusions— Although RI reflects the atherosclerotic process in an indirect manner, the correlation between the RI ICA and the SMART atherosclerosis score as well as the ability to distinguish between low- and high-risk patients are comparable to those of the well-known IMT.

Prediction of Cardiovascular Morbidity and Mortality Comparison of the Internal Carotid Artery Resistive Index With the Common Carotid Artery Intima-Media Thickness

Background and Purpose— The intima-media thickness (IMT) of the common carotid artery (CCA) is well correlated with the degree of arteriosclerosis and is a predictor of cardiovascular morbidity and mortality. The (hemodynamic) resistive index (RI) of the internal carotid artery (ICA) correlates with the degree of arteriosclerosis just as well as IMT. The aim of the study was to compare the predictive values of RI and IMT with regard to cardiovascular morbidity and mortality. Methods— A total of 146 patients with cardiovascular risk factors or established arteriosclerosis were included. Duplex sonography of the CCA and ICA was performed, and the IMT and RI were measured in both vessels. During follow-up for a median of 36 months, the occurrence of cardiovascular events (myocardial infarction, stroke, or cardiovascular death) was assessed. Results— Thirty-nine cardiovascular events occurred in 28 patients (19.2%). The relative risk for a cardiovascular event per increase of the IMT by 1 SD (0.16 mm) was 1.53 (95% CI, 1.07 to 2.18) and 1.91 (95% CI, 1.34 to 2.73) for RI ICA (0.08). The event rate in patients with IMT <0.79 mm (mean) and RI ICA <0.66 (mean) was 11.8% and 12.7% compared with 25.6% (P=0.03) and 25.0% (P=0.06) in patients with IMT ≥0.79 mm and RI ICA ≥0.66, respectively. Log rank analysis showed a continuous increase in the risk of cardiovascular event with increasing range of the IMT (P=0.029) and RI ICA (P<0.001). Conclusion— The RI ICA is a predictor of cardiovascular mortality and morbidity, at least comparable to the well-established IMT.

Noninvasive Imaging of the Vulnerable Atherosclerotic Plaque

Atherosclerosis is an inflammatory disease, complicated by progressively increasing atherosclerotic plaques that eventually may rupture. Plaque rupture is a major cause of cardiovascular events, such as unstable angina, myocardial infarction, and stroke. A number of noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify so-called vulnerable atherosclerotic plaques that are prone to rupture. The purpose of the present review is to systematically investigate the accuracy of noninvasive imaging techniques in the identification of plaque components and morphologic characteristics associated with plaque vulnerability, assessing their clinical and diagnostic value.

Skeletal muscle BOLD MRI: from underlying physiological concepts to its usefulness in clinical conditions.

Blood oxygenation‐level dependent (BOLD) MRI has gained particular attention in functional brain imaging studies, where it can be used to localize areas of brain activation with high temporal resolution. To a higher degree than in the brain, skeletal muscles show extensive but transient alterations of blood flow between resting and activation state. Thus, there has been interest in the application of the BOLD effect in studying the physiology of skeletal muscles (healthy and diseased) and its possible application to clinical practice. This review outlines the potential of skeletal muscle BOLD MRI as a diagnostic tool for the evaluation of physiological and pathological alterations in the peripheral limb perfusion, such as in peripheral arterial occlusive disease. Moreover, current knowledge is summarized regarding the complex mechanisms eliciting BOLD effect in skeletal muscle. We describe technical fundaments of the procedure that should be taken into account when performing skeletal muscle BOLD MRI, including the most often applied paradigms to provoke BOLD signal changes and key parameters of the resulting time courses. Possible confounding effects in muscle BOLD imaging studies, like age, muscle fiber type, training state, and drug effects are also reviewed in detail. J. Magn. Reson. Imaging 2012;35:1253–1265.

Contrast-enhanced ultrasound for assessing carotid atherosclerotic plaque lesions

OBJECTIVE Contrast-enhanced ultrasound that is used to assess atherosclerotic carotid plaques improves visualization of vessel wall irregularities and provides direct visualization of intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the assessment of carotid atherosclerotic lesions. CONCLUSION Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for evaluating both the development and severity of systemic atherosclerotic disease.

Contrast-enhanced ultrasound for imaging vasa vasorum: comparison with histopathology in a swine model of atherosclerosis.

AIM To evaluate the agreement between contrast-enhanced ultrasound imaging and histopathology in an animal model of atherosclerosis. METHODS AND RESULTS Atherosclerosis was studied in both femoral arteries of four Rapacz familial hypercholesterolaemia (RFH) swine. Contrast-enhanced ultrasound imaging of the eight femoral arteries was performed at baseline and at 5, 12, 26, and 43 weeks follow-up after percutaneous transluminal stimulation of atherosclerosis to assess the progression of intima-media thickness (IMT) and the density and extent of the vasa vasorum network. Contrast-enhanced ultrasound imaging allowed an early detection of atherosclerosis and showed a significant gradual progression of atherosclerosis over time. IMT increased from 0.22 +/- 0.05 mm at baseline to 0.45 +/- 0.06 mm (P < 0.001) at follow-up. The density of the vasa vasorum network increased during follow-up and was significantly higher in advanced than in early atherosclerosis. The findings with contrast-enhanced ultrasound were confirmed by histopathological specimens of the arterial wall. CONCLUSION Contrast-enhanced ultrasound is effective for in vivo detection of vasa vasorum in atherosclerotic plaques in the RFH swine model. After stimulation of atherosclerosis, contrast-enhanced ultrasound demonstrated a significantly increased IMT and significantly increased density of the vasa vasorum network in the developing atherosclerotic plaque, which was validated by histology.

Use of copeptin in the detection of myocardial ischemia

BACKGROUND The role of the arginine-vasopressin (AVP) system in the response to myocardial ischemia is unclear. Copeptin, the C-terminal part of the AVP prohormone is secreted stoichiometrically with AVP. METHODS A total of 253 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. We evaluated the response of copeptin during exercise and determined whether measurement of copeptin may be helpful in the detection of myocardial ischemia. RESULTS Myocardial ischemia on perfusion images was detected in 127 patients (50%). Median copeptin levels increased significantly with exercise in patients with ischemia as well as in patients without ischemia (from 3.8 [IQR 2.8-6.6] to 12.3 [IQR 5.2-39.6] pmol/l, P<0.001; and from 3.6 [IQR 2.6-5.7] to 10.8 [IQR 5.0-24.5] pmol/l, P<0.001). Median exercise-induced changes in copeptin (Deltacopeptin) were similar in both groups (7.7 versus 5.1 pmol/l, P=0.150). The area under the ROC curve for the ability of Deltacopeptin to detect myocardial ischemia was 0.552. CONCLUSIONS Copeptin levels increased threefold with exercise, irrespective of the presence or absence of myocardial ischemia. Therefore, myocardial ischemia does not seem to be a major trigger of the AVP system. Measurement of copeptin does not seem helpful in the detection of exercise-induced myocardial ischemia.