Second-generation Ultrasound Contrast Agent Research Articles

Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study

Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

Diagnosis of pancreatic tumors by endoscopic ultrasonography

Pancreatic tumors are highly diverse, as they can be solid or cystic, and benign or malignant. Since their imaging features overlap considerably, it is often difficult to characterize these tumors. In addition, small pancreatic tumors, especially those less than 2 cm in diameter, are difficult to detect and diagnose. For characterizing pancreatic tumors and detecting small pancreatic tumors, endoscopic ultrasonography (EUS) is the most sensitive of the imaging procedures currently available. This technique also provides good results in terms of the preoperative staging of pancreatic tumors. EUS-guided fine needle aspiration (EUS-FNA) has also proved to be a safe and useful method for tissue sampling of pancreatic tumors. Despite these advantages, however, it is still difficult to differentiate between benign and malignant, solid or cystic pancreatic tumors, malignant neoplasms, and chronic pancreatitis using EUS, even when EUS-FNA is performed. Recently, contrast-enhanced EUS with Doppler mode (CE-EUS) employing ultrasound contrast agents, which indicate vascularization in pancreatic lesions, has been found to be useful in the differential diagnosis of pancreatic tumors, especially small pancreatic tumors. However, Doppler ultrasonography with contrast-enhancement has several limitations, including blooming artifacts, poor spatial resolution, and low sensitivity to slow flow. Consequently, an echoendoscope was developed recently that has a broad-band transducer and an imaging mode that was designed specifically for contrast-enhanced harmonic EUS (CEH-EUS) with a second-generation ultrasound contrast agent. The CEH-EUS technique is expected to improve the differential diagnosis of pancreatic disease in the future. This review describes the EUS appearances of common solid and cystic pancreatic masses, the diagnostic accuracy of EUS-FNA, and the relative efficacies and advantages of CE-EUS and CEH-EUS along with their relative advantages and their complementary roles in clinical practice.

Evaluation of Renal Microcirculation by Contrast-Enhanced Ultrasound With SonazoidTM as a Contrast Agent Comparison Between Normal Subjects and Patients With Chronic Kidney Disease

Chronic kidney disease (CKD) is a major and serious risk factor for cardiovascular disease (CVD). Continuous hypoxia due to hypoperfusion in peritubular capillaries is one of the factors aggravating CKD, but evaluation of perfusion in this region is difficult using clinically available imaging methods. Since the second-generation ultrasound contrast agent Sonazoid has a stable shell, it enables visualization of the renal vasculature for a long period of time. We therefore evaluated changes in contrast-enhanced ultrasound (CEUS) imaging with Sonazoid in CKD patients.Sonazoid was used in 85 CKD patients and 5 control subjects, and images were recorded for 10 minutes. Time-intensity curves were generated from the images of 62 time points in both cortex and medulla.In control samples, contrast enhancement spread from the hilar portion to the periphery along the direction of arterial flow, and renal cortex and medulla were then enhanced in sequence. Enhancement was maximal soon after, then gradually decreased, but was still visible at 600 seconds. In CKD patients, renal contrast enhancement was attenuated in both cortex and medulla. On time-intensity curves, the attenuation of enhancement was composed of delayed rising, reduction of peak, and acceleration of decay in both cortex and medulla with progression of renal dysfunction. No side effects of the contrast agent were observed in any subjects.The attenuation of renal contrast enhancement observed in CKD patients appears to reflect disturbance of perfusion in peritubular capillaries. CEUS with Sonazoid is a useful and safe means of visualizing the renal microvasculature.

Evaluation of posttreatment response of hepatocellular carcinoma: comparison of ultrasonography with second-generation ultrasound contrast agent and multidetector CT

We evaluated the ability of one-month follow-up contrast-enhanced ultrasound (CEUS) with second-generation contrast agent in monitoring radio frequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) treatments of hepatocellular carcinoma (HCC). One-hundred forty-eight HCCs were studied using CEUS: 110 nodules were treated with RFA [41/110 RFA were performed using a pretreatment and an immediate postablation evaluation using CEUS (group 1); 69/110 using only US guidance (group 2)] and 38 nodules treated with TACE. For statistical analysis, McNemar test was used. Overall complete response was observed in 107/148 nodules (92/110 treated with RFA and 15/38 with TACE). A better rate of complete response was found in group 1 compared to group 2 (92.7% vs. 78.3%). In RFA treatment, CEUS showed a sensitivity of 83.3% and a specificity of 100% (diagnostic accuracy of 97%) using MDCT as reference standard with no statistical difference (p > 0.05). CEUS detected all cases of incomplete response in HCC treated with TACE using angiography as reference standard (diagnostic accuracy 100%). We recommend assessing residual intratumoral flow on CEUS during RFA procedure to determine the necessity of immediate additional treatment. In case of positive CEUS results, HCC treated with TACE should be considered still viable.

Real-Time Myocardial Contrast Echocardiography in Rat: Infusion Versus Bolus Administration

To compare the feasibility of real-time myocardial contrast echocardiography (MCE) in rats with infusion and bolus administration of a second-generation ultrasound contrast agent BR1. B-mode real-time MCE was performed in 12 Sprague Dawley rats following the BR1 infusion or bolus injection. The myocardium signal intensity (SI) was plotted against time and was fitted to exponential functions. The plateau SI (A) and rate of SI increase (β) for the infusion study and peak signal intensity (PSI) for the bolus study were obtained. 99mTc-Sestamibi and Evans blue were used to assess myocardial blood perfusion and to calculate the myocardium perfusion defect area ex vivo. High-quality real-time MCE images were successfully obtained using each method. At baseline, all LV segments showed even contrast distribution. Following left anterior descending coronary artery (LAD) ligation, significant perfusion defect was observed in LAD beds with a significantly decreased A* β and PSI values compared with LCx beds (Infusion: A*β LAD: 5.42 ± 1.57dB, A*β LCx: 46.52 ± 5.32dB, p < 0.05; Bolus: PSI LAD: 2.11 ± 0.67dB, PSI LCx: 20.68 ± 0.72 dB, p < 0.05), which was consistent with 99mTc-Sestamibi distribution findings. Myocardial perfusion defect areas, assessed by both methods, showed no differences and showed good correlation with Evans blue staining. ED frames were more favorable for imaging analysis. Both infusion and bolus administration of the contrast agent combined with real-time MCE technique can provide a reliable and noninvasive approach for myocardial perfusion assessment in rats and the infusion method was more suitable for quantitative analysis of myocardial blood flow. (E-mail: suhaili@fmmu.edu.cn)

Harmonic voiding urosonography with a second-generation contrast agent for the diagnosis of vesicoureteral reflux

Voiding urosonography with harmonic imaging (VUS HI) has been introduced as a sensitive and radiation-free imaging method for the diagnosis and follow-up of vesicoureteral reflux (VUR) in children. The purpose of this study was to evaluate the sensitivity of VUS HI using a second-generation US contrast agent compared to standard voiding cystourethrography (VCUG). A total of 228 children with 463 kidney-ureter units (KUUs) underwent two cycles of VUS HI and two cycles of VCUG at the same session. VUS HI was performed after intravesical administration of 1 ml of a second-generation US contrast agent (sulphur-hexafluoride gas microbubbles, SonoVue, Bracco, Italy). For statistical analysis we used McNemar's test, Student's t-test and k coefficient tests. VUR was shown in 161/463 (34.7%) KUUs, 57 by both methods, 90 only by VUS, and 14 only by VCUG. Concordance in findings regarding the presence or absence of VUR was found in 359/463 (77.5%) KUUs (k=0.40). The difference in the detection rate of reflux between the two methods was significant (P<0.01). More importantly, reflux missed by VCUG was of higher grade (2 grade I, 65 grade II, 19 grade III, 4 grade IV) than that missed by VUS (8 grade I, 5 grade II, 1 grade III). VUS HI and a second-generation contrast agent improved the identification of reflux in children. Our data reveal a higher sensitivity of the method compared to VCUG. Thus it can be used as an alternative radiation-free imaging method.

Detection and characterization of focal liver lesions with contrast-enhanced ultrasonography in patients with hepatitis c-induced liver cirrhosis

Hepatitis C virus (HCV)-associated liver cirrhosis provides a major preneoplastic condition for hepatocellular carcinoma (HCC). Ultrasonography (US) is usually used for screening of HCC, but needs improvement. To assess whether use of a second-generation ultrasound contrast agent can improve characterization of focal liver lesions and detection of HCC in HCV-infected patients with liver cirrhosis. In total, 96 US studies in 49 HCV-infected patients with liver cirrhosis were performed. The patients were first examined with a baseline US. After this, a diagnostic decision was made and recorded. The patients were then re-examined with contrast-enhanced ultrasound (CEUS), and the diagnostic triage was repeated. The patients were followed up for at least 1 year. On baseline US, indeterminate focal lesions were found in 27 examinations. After CEUS, a confident diagnosis of HCC was made in eight of these examinations. In an additional eight US examinations, diagnosis of regenerative/dysplastic noduli was established. In one patient with no detectable focal lesion at baseline examination, an indeterminate malignant lesion was detected with CEUS. This lesion was further investigated with computed tomography and diagnosed as HCC. Our study indicates that the use of CEUS significantly improves diagnostic confidence. CEUS improves the detection of HCC in patients with HCV-induced liver cirrhosis. Also, CEUS makes it possible to rule out malignancy in many cases where baseline US shows indeterminate focal lesions. In low-endemic countries, the use of CEUS in screening for HCC may be considered.

Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model

ObjectiveTumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.Materials and MethodsThe alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.ResultsThe pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).ConclusionContrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.

The Acute Effect of an Echo-Contrast Agent on Right Ventricular Dimensions and Contractility in Pigs

: The aim of the present study was to examine the effect of the second-generation ultrasound contrast agent (2nd GUCA) SonoVue on right ventricular (RV) dimensions and contractility and to investigate whether a dose-related interaction exists between the contrast agent and RV function. : Twenty-eight pigs were randomly assigned to 3 groups for intravenous administration: a low-dose group (0.5 cc of SonoVue), a high-dose group (1 cc of SonoVue), and a control group (2 cc of normal saline). RV end-diastolic (EDD) and end-systolic dimension (ESD) and pulmonary pressure (PP) were measured, and the fractional shortening (FS%) was calculated before the administration of SonoVue or normal saline and after the return of the RV-EDD or PP to the baseline value. The time to reach maximal RV-EDD or PP value and the time until the return of RV-EDD or PP to the baseline value were also measured. : Contrast agent infusion was followed by an acute transient increase of RV-EDD, RV-ESD, FS, and PP in both the low-dose and high-dose groups, but the increase was greater in the high-dose group. FS and PP did not change significantly in the control group. A dose-dependent delay in the time from baseline to maximum RV-EDD and PP was detected in the high-dose group (P < 0.001 for both) as well as a delay in the return from maximum to the baseline values (P < 0.001 for both). : Administration of the 2nd GUCA SonoVue is associated with an acute, transient, dose-dependent RV dilatation and an increase in pulmonary pressure with a consequent impact on RV contractility.

Recent advances in the diagnosis of hepatocellular carcinoma

In the last decade, new imaging techniques have become available, offering the possibility of investigating contrast perfusion of liver nodules in cirrhosis. It is now accepted that a non-invasive diagnosis of hepatocellular carcinoma (HCC) can be established based on the vascular pattern, obtained with pure blood pool contrast agents. The diagnostic pattern includes: hypervascularity in the arterial phase (15-35 s after contrast injection), consisting in a contrast signal in the nodule greater than in the surrounding parenchyma, followed by contrast wash out, which leads the nodule to show the same, or, more specifically, a lower contrast signal, than the surrounding parenchyma in the portal and late phases (>40 s after injection). Such a pattern can be obtained not only by computed tomography or magnetic resonance imaging, but also by contrast-enhanced ultrasonography, most simply with real-time low mechanical index harmonic imaging ultrasound equipment with second-generation ultrasound contrast agents. The risk of false-positive diagnosis of malignancy isnearly abolished when the functional vascular pattern is not the only feature, but is superimposed on a nodule visible also without contrast. One single contrast imaging technique may suffice to make a diagnosis of HCC if the nodule is >1 cm in diameter and has developed during a surveillance program. Other types of contrast agents, such as those taken up by the reticular-endothelial system cells, may offer additional diagnostic clues, but definitive evidence of their efficacy is still to be produced. In conclusion, contrast-enhanced imaging techniques now offer the possibility of a non-invasive diagnosis of HCC in a large number of cases, reducing the need of invasive investigations, such as ultrasound-guided biopsy or angiography.

Contrast enhanced ultrasound with second generation contrast agent for the follow-up of lower-extremity muscle-strain-repairing processes in professional athletes

In literature, ultrasonographic potentials in traumatic muscle lesions have been codified, whereas the data about this method utility in follow-up are dissonant. The purpose of this work is to evaluate a second-generation ultrasound (US) contrast agent rule for the professional athletes' distractive lesions. Twenty professional athletes (18 men and two women, aged between 18 and 34 years) affected by different muscle lesions were examined. All the patients were evaluated within 48 h of the trauma by US device Esaote Technos MPX with a high-frequency linear probe. The examinations were carried out with and without contrast agent after 20, 40 and 60 days after the trauma; second-generation contrast agent was used (SonoVue). In all athletes (nine first-grade lesions, 11 second-grade lesions), by using contrast agent intravenous injection done after 20 days, the appearance of contrast spots affecting part or all the lesioned area were observed. During the follow-up, after 40 days. the contrast spots widened to include the entire scar area, with haemorrhagic residual in three cases. After 60 days, in no case was a liquid haemorrhagic collection still present, and we found an important reduction of extension of vascular spots and US intensity and their total disappearance in seven cases. US with a second-generation contrast agent, thanks to the neoangiogenesis identification, allows recognition, individuation and monitoring the repair processes in the muscle lesion and allows estimation of when athletes can return to competitive activity. This fact obviously reduces both relapses and complications.

Voiding urosonography with ultrasound contrast agents for the diagnosis of vesicoureteric reflux in children. I. Procedure.

Voiding urosonography (VUS) encompasses examination of the urinary tract with intravesical administration of US contrast agent (UCA) for diagnosis of vesicoureteric reflux (VUR). The real breakthrough for US examination of VUR came with the availability of stabilized UCAs in the mid-1990s. This article presents a comprehensive review of various procedural aspects of VUS. Different US modalities are available for detecting the echogenic microbubbles: fundamental mode, colour Doppler US, harmonic imaging and dedicated contrast imaging with multiple display options. The reflux is graded (1 to 5) in a similar manner to the system used in voiding cystourethrography (VCUG). The most commonly used UCA for VUS, Levovist, is galactose-based and contains air-filled microbubbles. The recommended concentration is 300 mg/ml at a dose of 5–10%, or less than 5%, of the bladder filling volume when using fundamental or harmonic imaging modes, respectively. There are preliminary reports of VUS using a second-generation UCA, SonoVue. Here the UCA volume is less than 1% of the bladder filling volume. There is no specific contraindication to intravesical administration of UCA. The safety profile of intravesical Levovist is very high with no reports of side effects over a decade of use in VUS.

Detection of Colorectal Cancer Hepatic Metastases with Contrast-Enhanced Ultrasound: Comparison with Conventional B-Mode Ultrasound

The aim of this study was to assess whether contrast-enhanced ultrasound (CE-US) could provide improved diagnostic information in detecting liver metastases from colorectal cancer as compared to B-mode non-enhanced ultrasound (B-US). 32 patients (M/F 23/9, age range 48–82 years, mean 58.2 years) under chemotherapy for colorectal cancer were examined with B-US and CE-US using a second-generation ultrasound contrast agent and a dedicated protocol for contrast detection. The presence of focal liver lesions along with the number, size, pre- and post-contrast sonographic features were recorded digitally. Lesion conspicuity with a three-grade scoring scale was performed on both techniques and contrast intensity measurements were calculated for each focal lesion. CE-US detected 17% more metastases in patient-by-patient and lesion-by-lesion analysis. A statistically significant difference was found between the scoring mean values with regard to conspicuity of the lesions. Accurate characterization of the liver lesions was achievable only with contrast-enhanced technique. A quantitative contrast intensity measurement method confirmed the invariably washing-out vascular pattern in all metastases at sinusoidal-parenchymal liver phase. In conclusion, CE-US is superior to B-US and provides an effective tool in the investigation of colorectal cancer liver metastases.

The safety of Sonovue® in abdominal applications: Retrospective analysis of 23188 investigations

The aim of the present retrospective study was to assess the incidence of adverse events (AE) of a second-generation ultrasound contrast agent in real clinical practice. A total of 28 Italian Centres provided data on the postmarketing use of SonoVue® (Bracco Spa, Milan, Italy) in abdominal examination performed between December 2001 and December 2004. A total of 23 188 investigations were reported. No fatal event occurred. AEs were reported in 29 cases, of which only two were graded as serious; the rest, 27, were nonserious (23 mild, three moderate and one severe). The overall reporting rate of serious AE was 0.0086%. Overall, only four AEs required treatment (two serious, two nonserious including one moderate and one severe AEs). In conclusion, the present large-scale retrospective analysis showed that SonoVue has a good safety profile in abdominal applications, with an AE reporting rate lower than or similar to that reported for radiologic and magnetic resonance contrast agents. (E-mail: Piscagl@med.unibo.it)

Freehand three-dimensional assessment of left ventricular volumes and ejection fraction with ultrasound contrast agent LK565

Accurate assessment of left ventricular function by determining left ventricular volumes and ejection fraction is important in evaluating the prognoses of patients with heart failure. Two-dimensional (2D) echocardiography suffers from low correlation with reference methods like ventriculography. Three-dimensionally (3D) assessed data have been proved to have better conformity. Endocardial border delineation remains a problem, however, especially in patients with suboptimal recordings. Few data exist on 3D-echocardiographic volumetry with ultrasound contrast agents (UCAs). We evaluated the second-generation UCA LK565 for its boundary-tracing capacities in freehand 3D echocardiography in a phase II clinical trial. Safety and efficacy of the novel contrast agent were also evaluated. Forty patients between the age of 42 and 77 were included in this trial. Left ventricular end-systolic and -diastolic volume (LVESV, LVEDV) and ejection fraction (EF) were determined by either 2D or 3D freehand second harmonic echocardiography with and without use of LK565. Parameters were compared statistically with ventriculography performed in 35 patients. Immune response to LK565 was evaluated by analysing phagocytosis capacity and kinetics of inflammatory cytokines (TNF-alpha, IL-4, IL-10, IFN-gamma). Patients were monitored for adverse events up to 72 h after application of the UCA. Calculated values for left ventricular volumes and ejection fraction correlated best for freehand 3D echocardiography in combination with LK565 (r=0.92 for LVEDV; r=0.96 for LVESV; r=0.94 for EF). Excellent left ventricular contrast enhancement was achieved for approximately 8 min. A reversible saturation of phagocytosis capacity for monocytes and neutrophils set in with a maximum peak at 6h. No significant increase in cytokine expression was observed. LK565 improves feasibility of endocardial border delineation in 3D echocardiography, leading to better correlation of left ventricular volumetry with reference methods. Efficacy and safety of LK565 are equivalent to those of conventional UCAs.

Ultrasonographic portography with low mechanical index gray-scale imaging in hepatic VX2 tumor

To evaluate the characteristics of portal blood supply of hepatic tumors by ultrasonographic portography (USP), an in vivo model was studied using SonoVue™, a second-generation ultrasound contrast agent (UCA) and low mechanical index (MI), gray-scale harmonic imaging. SonoVue™ (0.05 mL) was administrated through catheter placed into the main trunk of portal vein at laparotomy, followed by a 0.5 mL saline flush, in 12 rabbits with hepatic VX2 tumor, implanted by VX2 tumor tissue cubes of approximately 1 mm 3 from carrier rabbit. Results showed that low MI gray-scale imaging delineated clearly the dynamic enhancement of tumors and liver parenchyma. Among 22 tumors, seven tumors were diffusely increased, with the intensity of enhancement weaker than that of the surrounding liver parenchyma. The UCA was washed out earlier from tumors than from surrounding liver parenchyma. Three tumors showed the branches of portal vein. Five tumors showed peripheral contrast enhancement and a central coarse unenhanced hypoechoic area. Seven tumors displayed no actual enhancement. All lesions (100% [22 of 22]) were depicted clearly in the whole duration of enhancement, especially in the early and late phase, regardless of enhancement pattern, and portal blood flow was manifested in 15 of 22 (68%) tumors, by USP. The enhancement pattern of the tumors corresponded to the pathologic findings. The results indicated that ultrasonographic portography, combined with low MI levels and second-generation UCA, is a sensitive and safe method to study portal blood supply for liver cancer. It may contribute to improvement of the detectability and diagnostic ability and assist the choice of a therapeutic strategy for treatment of liver cancer. However, applicability of the method to human may be problematic because of high invasiveness and great difficulty in administering contrast medium. (E-mail: jieli301@hotmail.com)

L’angiosonografia nelle lesioni mammarie sospette con FNAC non diagnostico: confronto con eco Power Doppler

The purpose of this study was to evaluate the accuracy of angiosonography in comparison with colour Doppler ultrasound (US) in the discrimination of suspicious breast lesions with nondiagnostic fine-needle aspiration cytology (FNAC). Pre-operative Power Doppler US and angiosonography were prospectively performed in 20 suspicious breast lesions with non-diagnostic FNAC. A second-generation US contrast agent was utilised with a high-frequency transducer and a contrast-specific algorithm (low acoustic pressure CnTI). The enhancement characteristics of all lesions were analysed using qualitative and quantitative parameters obtained from time-intensity curves with the different imaging modalities. The final diagnosis was confirmed at pathology in all cases. Microvessel density (MVD) was assessed in the surgical specimen using CD34. The correct assessment of biological behaviour was achieved in all cases by angiosonography (sensitivity of 100%; specificity of 91%) and colour Doppler US (45% sensitivity; 78% specificity). MVD correlated with the biological behaviour. Angiosonography is more accurate than colour Doppler US in the correct assessment of biological behaviour of suspicious breast lesions.

Grey-scale contrast enhancement in rabbit liver with SonoVue™ at different doses

To evaluate the dose of ultrasound (US) contrast agent (UCA) in relation to the contrast-enhancement effect, an in vivo model of perfusion was studied using SonoVue™, a second-generation UCA, and low mechanical index (MI) grey-scale harmonic imaging. SonoVue™, at eight different doses (0.02, 0.04, 0.06, 0.08, 0.10, 0.12, 0.14 and 0.16 mL/kg BW), was applied in five normal rabbits. Flow-related parameters obtained from time-intensity curves were calculated and plotted over the contrast agent doses, and nonlinear curve fitting was performed. Results showed that, along with an increase of the administrated contrast agent dose, the enhancement duration (ED) and the area under the curve (AUC) increased logarithmically, and the time to enhancement (ET) decreased logarithmically. There was a progressive increase of the peak signal intensity (PSI) following an increase of SonoVue™ dose only in the dose range of 0.02 up to 0.10 mL/kg body weight (BW) in the portal vein and in the dose range of 0.02 up to 0.12 mL/kg BW in the liver parenchyma. Moreover, a good correlation was observed between the parameters obtained from liver parenchyma and those obtained from the portal vein. The results indicated that SonoVue™ in conjunction with continuous harmonic low-MI grey-scale imaging has the capability of flow quantification on both vessels and parenchyma. The parameters of time-intensity curve were influenced intensely by different contrast agent doses. (E-mail: jieli301@hotmail.com)

The use of contrast-enhanced ultrasound in the management of the cirrhotic patient and for detection of HCC

Hepatocellular carcinoma (HCC) is the leading cause of death in liver cirrhosis. Ultrasound (US) is widely accepted as the screening imaging modality of choice for HCC in patients with a history of chronic liver disease. However, the US characteristics of HCCs are non-specific and thus, other imaging techniques or biopsy are usually necessary to characterize focal liver lesions (FLL) and confirm malignancy. Blood flow to HCC is mainly arterial, making dynamic CT and MRI the most commonly used techniques to detect the characteristic arterial hypervascularization. Recently, the development of second-generation US contrast agents and microbubble-specific software has changed the role of US in real-time evaluation of the macro and microvascularization of FLLs. With this technology, the accuracy of US in the diagnosis of HCC and its differentiation from other FLLs such as regenerating nodules has improved dramatically. In addition, contrast-enhanced ultrasound may also be a useful tool in the staging of HCC and in the evaluation of percutaneous treatment.

Échographie de contraste des tumeurs hépatiques

Second-generation ultrasound contrast agents are gas microbubbles that are injected into a peripheral vein and enhance the backscattered ultrasound from the blood vessel lumen. The non-linear signal produced by the bubbles can be differentiated from the tissue signal. No severe adverse events have been reported, and these agents can be used in patients who are at high risk due to heart failure, renal failure, or pulmonary hypertension. In patients with liver disease, contrast-enhanced ultrasonography provides an evaluation of the microvessels within focal nodular lesions and a characterization of benign and malignant lesions similar in terms of semiology and reliability to that obtained with computed tomography. Second-generation contrast agents substantially improve the results of ultrasonography for detecting and quantifying liver metastases. Adaptations to the ultrasound equipment must be made to allow use of these agents.