Irreversible Electroporation for Hepatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

PURPOSE: A consensus study of panelists was performed to provide a uniform protocol regarding (contra) indications, procedural parameters, perioperative care, and follow-up of irreversible electroporation (IRE) for the treatment of hepatic malignancies. MATERIALS AND METHODS: Interventional radiologists who had 2 or more publications on IRE, reporting at least 1 patient cohort in the field of hepatobiliary IRE, were recruited. The 8 panelists were asked to anonymously complete 3 iterative rounds of IRE-focused questionnaires to collect data according to a modified Delphi technique. Consensus was defined as having reached 80% or greater agreement. RESULTS: Panel members' response rates were 88%, 75%, and 88% in rounds 1, 2, and 3, respectively; consensus was reached on 124 of 136 items (91%). Percutaneous or intraoperative hepatic IRE should be considered for unresectable primary and secondary malignancies that are truly unsuitable for thermal ablation because of proximity to critical structures. Absolute contraindications are ventricular arrhythmias, cardiac stimulation devices, and congestive heart failure of New York Heart Association class 3 or higher. A metal stent outside the ablation zone should not be considered a contraindication. For the only commercially available IRE device, the recommended settings are an inter-electrode distance of 10-20 mm and an exposure length of 20 mm. After 10 test pulses, 90 treatment pulses of 1500 V/cm should be delivered continuously, with a pulse length of 70-90 µs. The first post-procedural follow-up should take place 1 month after IRE and thereafter every 3 months, using cross-sectional imaging plus tumor marker assessment. CONCLUSIONS: This article provides recommendations, created by a modified Delphi consensus study, regarding patient selection, workup, procedure, and follow-up of IRE treatment for hepatic malignancies.

Evaluation of Perfusion Quantification Methods with Ultrasound Contrast Agents in a Machine-Perfused Pig Liver.

PURPOSE: To evaluate dynamic contrast-enhanced ultrasound (DCEUS) as a tool for measuring blood flow in the macro- and microcirculation of an ex-vivo machine-perfused pig liver and to confirm the ability of DCEUS to accurately detect induced flow rate changes so that it could then be used clinically for monitoring flow changes in liver tumors. MATERIALS AND METHODS: Bolus injections of contrast agents in the hepatic artery (HA) and portal vein (PV) were administered to 3 machine-perfused pig livers. Flow changes were induced by the pump of the machine perfusion system. The induced flow rates were of clinical relevance (150 - 400 ml/min for HA and 400 - 1400 ml/min for PV). Quantification parameters from time-intensity curves [rise time (RT), mean transit time (MTT), area under the curve (AUC) and peak intensity (PI)] were extracted in order to evaluate whether the induced flow changes were reflected in these parameters. RESULTS: A linear relationship between the image intensity and the microbubble concentration was confirmed first, while time parameters (RT and MMT) were found to be independent of concentration. The induced flow changes which propagated from the larger vessels to the parenchyma were reflected in the quantification parameters. Specifically, RT, MTT and AUC correlated with flow rate changes. CONCLUSION: Machine-perfused pig liver is an excellent test bed for DCEUS quantification approaches for the study of the hepatic vascular networks. DCEUS quantification parameters (RT, MTT, and AUC) can measure relative flow changes of about 20 % and above in the liver vasculature. DCEUS quantification is a promising tool for real-time monitoring of the vascular network of tumors.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Short Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

Improvement of the accuracy of liver lesion DCEUS quantification with the use of automatic respiratory gating.

OBJECTIVES: To evaluate the efficiency of automatic respiratory gating (ARG) in reducing respiratory motion-induced artefacts from dynamic contrast-enhanced ultrasound (DCEUS) acquisitions and to assess the impact of ARG on DCEUS quantification parameters in patients with liver malignancies. METHODS: Twenty-five patients with liver metastasis were imaged with DCEUS. The lognormal indicator dilution model was fitted on time-intensity curves extracted from hepatic lesions with and without the use of ARG and DCEUS quantification parameters were extracted. The goodness of fit was assessed using the coefficient of determination (R (2) LN ). The effect respiration had on the data was assessed using the respiration amplitude (RA) metric. Pearson's correlation coefficient (r) was used to assess the correlation between R (2) LN and RA with and without the use of ARG. RESULTS: The RA parameter was strongly correlated with R (2) LN (r = -0.96, P = 7.412 × 10(-15)) and this correlation became weaker with ARG (r = -0.64, P = 5.449 × 10(-4)). ARG significantly influenced the values of the quantification parameters extracted (P ≤ 0.05). The RA was significantly decreased when ARG was used (P = 1.172 × 10(-6)). CONCLUSIONS: ARG has a significant impact on the quantification parameters extracted and it has been shown to improve the accuracy of liver lesion DCEUS. KEY POINTS: • ARG has a significant impact on DCEUS quantification parameters. • ARG can improve the modelling of liver lesion haemodynamics using DCEUS quantification. • ARG significantly reduces the respiration amplitude of DCEUS lesion time-intensity curves.

Early Diagnosis of Intrahepatic Pseudoaneurysm during Radiofrequency Ablation using Contrast-Enhanced Ultrasound.

Radiofrequency ablation is one of the more established forms of local treatment in patients with unresectable tumours, including colorectal hepatic metastases. Complications associated with this method of intervention include thermal and mechanical injuries, including vascular insults resulting in haemorrhage or pseudoaneurysm formation. This is the first case demonstrating the detection of post-ablation acute pseudoaneurysm formation identified on the table using contrast-enhanced ultrasound (CEUS) and the subsequent successful management.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Introduction of genes via sonoporation and electroporation.

Gene therapy delivery using viral vectors has demonstrated efficient transfection but has safety issues. The need for safer yet effective delivery systems has led to the active development of non-viral techniques. In this chapter, we will discuss two evolving techniques - sonoporation with microbubble contrast agents and electroporation with focus on their basic principle, parameters affecting delivery efficiency, current evolving techniques and future prospects.

Consensus Guidelines of Irreversible Electroporation for Pancreatic Tumors: Protocol Standardization Using the Modified Delphi Technique.

Since no uniform treatment protocol for pancreatic irreversible electroporation (IRE) exists, the heterogeneity throughout literature complicates the comparison of results. To reach agreement among experts, a consensus study was performed. Eleven experts, recruited according to predefined criteria regarding previous IRE publications, participated anonymously in three rounds of questionnaires according to a modified Delphi technique. Consensus was defined as having reached ≥80% agreement. Response rates were 100, 64, and 64% in rounds 1 to 3, respectively; consensus was reached in 93%. Pancreatic IRE should be considered for stage III pancreatic cancer and inoperable recurrent disease after previous local treatment. Absolute contraindications are ventricular arrhythmias, implantable stimulation devices, congestive heart failure NYHA class 4, and severe ascites. The inter-electrode distance should be 10 to 20 mm and the exposure length should be 15 mm. After 10 test pulses, 90 treatment pulses of 1,500 V/cm should be delivered continuously, with a 90-µs pulse length. The first postprocedural contrast-enhanced computed tomography should take place 1 month post-IRE, and then every 3 months. This article provides expert recommendations regarding patient selection, procedure, and follow-up for IRE treatment in pancreatic malignancies through a modified Delphi consensus study. Future studies should define the maximum tumor diameter, response evaluation criteria, and the optimal number of preoperative FOLFIRINOX cycles.

Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma.

Primary aldosteronism (PA) is the most prevalent form of secondary hypertension and is most commonly caused by an adrenal adenoma or bilateral adrenal hyperplasia. Minimally invasive adrenalectomy is the treatment of choice for unilateral disease. Here, we report the case of a 57-year-old man with previous bladder cancer who was referred for evaluation of resistant hypertension and hypokalemia. Diagnostic workup indicated PA with computed tomography imaging revealing a left adrenal adenoma and adrenal venous sampling lateralizing to the left adrenal. He was therefore referred for a left adrenalectomy using a retroperitoneoscopic approach. However, surgery was complicated by significant perinephritis related to previous bladder cancer immunotherapy and, in view of an identifiable adrenal adenoma, a partial adrenalectomy was performed. Despite histology confirming removal of an adrenal adenoma, he remained hypertensive and hypokalemic with persistent PA. He underwent a computed tomography-guided percutaneous thermal (microwave) ablation of the residual adrenal nodule with immediate biochemical reversal of PA. Six years postprocedure, he remains biochemically and clinically cured from PA. This article presents the details of the case and reviews the literature on long-term outcomes for patients undergoing thermal ablation and adrenalectomy, suggesting that thermal ablation may be a viable alternative for selected patients.

Dexamethasone arterializes venous endothelial cells by inducing mitogen-activated protein kinase phosphatase-1: a novel antiinflammatory treatment for vein grafts?

BACKGROUND: Vein grafting in coronary artery surgery is complicated by a high restenosis rate resulting from the development of vascular inflammation, intimal hyperplasia, and accelerated atherosclerosis. In contrast, arterial grafts are relatively resistant to these processes. Vascular inflammation is regulated by signaling intermediaries, including p38 mitogen-activated protein (MAP) kinase, that trigger endothelial cell (EC) expression of chemokines (eg, interleukin-8, monocyte chemotactic protein-1) and other proinflammatory molecules. Here, we have tested the hypothesis that p38 MAP kinase activation in response to arterial shear stress (flow) may occur more readily in venous ECs, leading to greater proinflammatory activation. METHODS AND RESULTS: Comparative reverse-transcriptase polymerase chain reaction and Western blotting revealed that arterial shear stress induced p38-dependent expression of monocyte chemotactic protein-1 and interleukin-8 in porcine jugular vein ECs. In contrast, porcine aortic ECs were protected from shear stress-induced expression of p38-dependent chemokines as a result of rapid induction of MAP kinase phosphatase-1. However, we observed with both cultured porcine jugular vein ECs and perfused veins that venous ECs can be protected by brief treatment with dexamethasone, which induced MAP kinase phosphatase-1 to suppress proinflammatory activation. CONCLUSIONS: Arterial but not venous ECs are protected from proinflammatory activation in response to short-term exposure to high shear stress by the induction of MAP kinase phosphatase-1. Dexamethasone pretreatment arterializes venous ECs by inducing MAP kinase phosphatase-1 and may protect veins from inflammation.

Dose-dependent artifact in the far wall of the carotid artery at dynamic contrast-enhanced US.

PURPOSE: To quantify a pseudoenhancement phenomenon observed during dynamic contrast material-enhanced ultrasonography (US) of the carotid artery, both in vitro and in vivo. MATERIALS AND METHODS: Ethical approval was obtained prior to commencing this prospective case series, and each patient gave written informed consent. Thirty-one patients with 50%-99% internal carotid artery stenosis underwent dynamic contrast-enhanced US of the carotid bifurcation with use of 2 mL of microbubbles. In the final 10 patients, an additional 1 mL bolus was administered after 15 minutes. Raw linear digital imaging and communications in medicine data were analyzed offline. Regions of interest were drawn within the common carotid artery lumen and immediately adjacent to the lumen in the near and far wall adventitia. Peak intensity was measured. An in vitro experiment with a single-channel flow phantom was also performed. This apparatus consisted of an 8-mm-diameter latex tube placed in a tissue-mimicking fluid. Microbubble concentrations of 0.02%, 0.1%, 0.5%, 1%, and 2% were pumped into the tube. Regions of interest were drawn in a similar fashion to the in vivo experiments, and peak intensity was measured. The Wilcoxon signed rank and paired t tests were used to compare the difference between the near and far wall signal intensities at each dose; a multiplication factor comparing near and far wall signal intensity was derived. RESULTS: The far wall of the common carotid artery was significantly more echogenic than the near wall at 2 mL contrast agent doses (P<.0001, n=31), and the far wall signal intensity increased synchronously with that of the lumen. The difference in signal intensity between near and far wall regions was significantly greater at 2 mL than at 1 mL (P=.012, n=10). In vitro, the phantom tubing demonstrated a similar pattern and magnitude of enhancement to that seen in vivo. CONCLUSION: A dose-dependent, nonlinear propagation artifact known as pseudoenhancement occurs in the far wall adventitia of the carotid artery and should not be mistaken as a marker of plaque vulnerability.

Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials.

Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

Reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound.

OBJECTIVES: The aim of this clinical study was to evaluate the reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound. METHODS: Fifteen patients with colorectal liver metastases and 5 volunteers were studied. The hepatic artery proper and the portal vein were imaged simultaneously with dynamic contrast-enhanced ultrasound. The examination was repeated with 2 different contrast bolus volumes (1.2 and 2.4 mL), and time-intensity curves were formed from dynamic contrast-enhanced ultrasound image loops. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Inter-reader, intra-reader, and inter-scan agreement was assessed by 2 independent readers. Quantitative (intraclass correlation coefficients and coefficients of variation [CVs]) and qualitative (Landis and Koch classification) analyses were performed. RESULTS: Intra-reader and inter-reader agreement was "almost perfect" for the hepatic artery (CV, 10%-15% and 8%-9%, respectively), portal vein (CV, 5%-8% and 6%-12%), and hepatic artery/portal vein ratio (CV, 8%-14% and 10%-15%) measurements of 3 all studied parameters. In contrast, inter-scan agreement was only "slight" to "moderate" (CV, 25%-27%) and "fair" to "moderate" (CV, 19%-24%) for rise time and peak intensity measurements in the hepatic artery and portal vein, respectively. CONCLUSIONS: Quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound is reproducible provided that measurements in the hepatic artery are normalized by those in the portal vein.

Late-phase contrast-enhanced ultrasound reflects biological features of instability in human carotid atherosclerosis.

BACKGROUND AND PURPOSE: Development of translational functional imaging modalities for atherosclerosis risk stratification is sought for stroke prediction. Our group has developed late-phase contrast-enhanced ultrasound (LP-CEUS) to quantify microbubble contrast retention within carotid atherosclerosis and shown it to separate asymptomatic plaques from those responsible for recent cerebrovascular events. We hypothesized that microbubbles are retained in areas of plaque inflammation, aiming to examine whether LP-CEUS signal reflects plaque biology. METHODS: Subjects awaiting carotid endarterectomy (n=31) underwent axial LP-CEUS and diseased intimal segments were symmetrically divided in the long axis. Half-specimens underwent quantitative immunohistochemical analysis for CD68 (macrophages) and CD31 (angiogenesis). Half-specimens were processed for atheroma cell culture and supernatant collected at 24 hours for multianalyte profiling for 34 analytes. RESULTS: Percentage area immunopositivity was significantly higher in subjects in which normalized plaque late-phase intensity was ≥0 versus <0 (CD68 mean 11.8 versus 6.68, P=0.004; CD31 mean 9.45 versus 4.82, P=0.025). Interleukin-6, matrix metalloproteinase-1, and matrix metalloproteinase-3 were significantly higher by multianalyte profiling when LP-CEUS was ≥0. CONCLUSIONS: LP-CEUS reflects biological features of inflammation and angiogenesis, key features predisposing to plaque rupture. Further investigation of LP-CEUS as a tissue-specific marker of inflammation for risk stratification of carotid atherosclerosis is warranted.

Contrast enhanced ultrasound in the detection of liver metastases: a prospective multi-centre dose testing study using a perfluorobutane microbubble contrast agent (NC100100).

OBJECTIVE: To conduct a dose testing analysis of perfluorobutane microbubble (NC100100) contrast-enhanced ultrasound (CEUS) to determine the optimal dose for detection of liver metastases in patients with extra-hepatic primary malignancy. METHODS: 157 patients were investigated with conventional US and CEUS. CEUS was performed following intravenous administration of perfluorobutane microbubbles (using one dose of either 0.008, 0.08, 0.12 or 0.36 µL/kg body weight). Three blinded off-site readers recorded the number and locations of metastatic lesions detected by US and CEUS. Contrast enhanced CT and MRI were used as the "Standard Of Reference" (SOR). Sensitivity, specificity and accuracy of liver metastasis detection with US versus CEUS, for each dose group were obtained. Dose group analysis was performed using the Chi-square test. RESULTS: 165 metastases were present in 92 patients who each had 1-7 lesions present on the SOR. Sensitivity of US versus CEUS (for all doses combined) was 38% and 67% (p = 0.0001). The 0.12 dose group with CEUS (78%) had significantly higher sensitivity and accuracy (70%) compared to other dose groups (p < 0.05). CONCLUSION: The diagnostic performance of CEUS is dose dependent with the 0.12 µL/kg NC100100 dose group showing the greatest sensitivity and accuracy in detection of liver metastases.

Multimodality imaging of neoplastic and nonneoplastic solid lesions of the pancreas.

Solid lesions of the pancreas represent a heterogeneous group of entities that can be broadly classified as either neoplastic or nonneoplastic. Neoplastic lesions include pancreatic adenocarcinoma, pancreatic neuroendocrine tumor, solid pseudopapillary tumor, pancreatoblastoma, pancreatic lymphoma, metastases to the pancreas, and rare miscellaneous neoplasms. Nonneoplastic lesions include focal pancreatitis, fatty infiltration-replacement, intrapancreatic accessory spleen, congenital anomalies such as prominent pancreatic lobulation and bifid pancreatic tail (pancreatic bifidum), and rare miscellaneous lesions (eg, pancreatic sarcoidosis, Castleman disease of the pancreas). A variety of imaging modalities are available for assessing these solid lesions, including ultrasonography (US), computed tomography (CT), magnetic resonance imaging, endoscopic US, and hybrid nuclear imaging techniques such as single photon emission computed tomography-CT and positron emission tomography-CT, each of which has its own strengths and limitations. Accurate diagnosis can be challenging, and use of a multimodality imaging approach is often helpful in equivocal or complex cases. Knowledge of relevant clinical information and key radiologic features is essential for confident lesion characterization and differentiation.

Assessment of global liver blood flow with quantitative dynamic contrast-enhanced ultrasound.

OBJECTIVES: This study assessed the potential of quantitative analysis of contrast bolus kinetics to reflect global liver blood flow. METHODS: A dynamic contrast-enhanced ultrasound flow phantom was developed. A peristaltic pump established constant volume flow ranging between 16.5 and 49.5 mL/min (2-mm tube) and 85.5 and 256.5 mL/min (5-mm tube). After bolus injection of 2 doses of a contrast agent, a region of interest was drawn over the cross section of the tube used for a particular acquisition; the rise time, peak intensity, and wash-in slope were derived from time-intensity curves. Twenty healthy volunteers and 25 patients with biopsy-proven colorectal liver metastases were scanned with dynamic contrast-enhanced ultrasound. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Hepatic artery/portal vein ratios of the parameters were also calculated. RESULTS: In the in vitro experiment, the rise time decreased while the peak intensity and wash-in slope increased with increasing volume flow for both tube diameters and contrast bolus volumes. In the clinical study, the rise time was lowered in the hepatic artery but elevated in the portal vein, and the peak intensity and wash-in slope were elevated in the hepatic artery but lowered in the portal vein in patients with colorectal liver metastases compared with healthy volunteers, although not in a statistically significant manner. This finding was consistent with an increase in hepatic artery blood flow, a decrease in portal vein blood flow, or both in patients with colorectal liver metastases compared with healthy volunteers. Only the 3 hepatic artery/portal vein ratios of the parameters achieved statistical significance in differentiating healthy volunteers from patients with colorectal liver metastases (P < .05). CONCLUSIONS: Surrogate measurements of liver blood flow may be derived from quantitative analysis of dynamic contrast-enhanced ultrasound studies. They may have potential for quick and easy assessment of altered hepatic hemodynamics.

Inflammation within carotid atherosclerotic plaque: assessment with late-phase contrast-enhanced US.

PURPOSE: To determine if the number of nontargeted microbubbles retained in human carotid plaque is sufficient 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 flash imaging with a nonlinear mode at an intermediate mechanical index of 0.34 6 minutes after bolus contrast agent injection. Plaques were defined 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 defined 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% confidence interval: -0.11, 0.89) than in the asymptomatic group (0.69; 95% confidence interval: -1.04, -0.34) (P = .0005). There was a moderate (rho = -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-specific marker of inflammation and a potential role in the risk stratification of atherosclerotic carotid stenosis.