Microbubble Contrast Agent SonoVue Research Articles

Microbubble contrast agent SonoVue: An efficient medium for the preoperative lymphatic mapping of thyroid carcinoma.

Objective: To assess the value of microbubble contrast agent SonoVue in the thorough preoperative lymphatic mapping of patients with thyroid carcinoma, including the lymphatic drainage region, the detection of sentinel lymph node (SLN), and the diagnosis of lymph node metastasis (LNM). Materials and methods: 55 patients with 62 thyroid malignancies proved by surgical pathology (59 papillary thyroid carcinomas and three medullary thyroid carcinomas) who underwent preoperative lymphatic contrast-enhanced ultrasound (LCEUS) with microbubble contrast agent SonoVue were enrolled. All LNM were confirmed by pathology. The location of thyroid lesions, ultrasonic features of lymph nodes, lymphatic drainage region, and detection of SLN were assessed. The diagnostic performance (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) of different parameters for the LNM diagnosis was calculated. Results: SonoVue effectively demonstrated the lymphatic drainage region for all enrolled thyroid carcinomas. The most common lymphatic drainage region for thyroid carcinomas was region VI (93.55%), followed by region III (62.90%), region IV (48.39%) and region II (4.84%). When divided by the lesion location, the most common lymphatic drainage regions for the nodule in isthmus, superior lobe and inferior lobe of the thyroid were region VI, region III, and region VI respectively. SLN was detected in 96.77% (60/62) of cases. The two cases without SLN demonstration had pathologically proven LNM. The most common sonographic sign of LNM was perfusion defect (54.17%). The diagnostic accuracy of SonoVue in central and lateral compartment LNM was 86.67% and 91.67%, respectively. Conclusion: Microbubble contrast agent SonoVue is a valuable imaging contrast medium for thorough preoperative lymphatic mapping in patients with thyroid carcinoma, including the lymphatic drainage region, the detection of SLN, and the diagnosis of LNM. LCEUS with SonoVue alone has limitations of false negatives when there is lymphatic vessel obstruction and may need to be combined with other ultrasound modalities.

Microbubble contrast agent SonoVue combined with oxytocin improves the efficiency of high-intensity focused ultrasound ablation for adenomyosis

Background To investigate the combined enhancing effects of microbubble-contrast SonoVue and oxytocin on high-intensity focused ultrasound (HIFU) ablation of adenomyosis. Methods 330 patients with adenomyosis were randomly assigned to SonoVue and oxytocin group (group A, n = 82), oxytocin (group B, n = 85), SonoVue (group C, n = 81), or the control (group D, n = 82) for HIFU ablation. In group A, oxytocin was dripped 0.32 IU/min, and HIFU ablation was started one minute after SonoVue injection. In group B, oxytocin was dripped 0.32 IU/min during ablation. In group C, HIFU ablation was started one minute after SonoVue injection. In group D, neither oxytocin nor SonoVue was applied. The clinical data, treatment results, and complications were analyzed. Results All participants underwent HIFU treatment safely, and the mean energy efficiency factor (EEF) in the four groups was 4.7 ± 0.9J/mm3, 8.5 ± 0.6J/mm3, 8.9 ± 0.7J/mm3, and 12.6 ± 1.8J/mm3, respectively, with the mean ablation time (AT) of 633.7 ± 55.1 s, 874.2 ± 65.6 s, 936.3 ± 85.2 s, and 1103.2 ± 96.2 s, respectively. The non-perfused volume ratios (NPVR) were 90.4 ± 8.8%, 88.7 ± 9.1%, 89.4 ± 7.2%, 80.5 ± 7.9%, respectively. In addition, EEF and AT were the shortest in group A (p < 0.05). NPVR was significantly higher in group A than in the control group D (p < 0.05). The incidence rates of adverse events were not significantly different in the four groups (p > 0.05). Conclusions Compared to the control group, oxytocin combined with SonoVue in HIFU for adenomyosis can significantly decrease the energy and time needed for the ablation and safely enhance the treatment efficiency by improving the cavitation and heating of HIFU ablation and increasing the non-perfused volume ratio.

Optimisation of the transmit beam parameters for generation of subharmonic signals in native and altered populations of a commercial microbubble contrast agent SonoVue®

The aim of this work was to establish the optimum acoustic characterisation approach and insonation transmit beam parameters for subharmonic signal generation with ‘native’ and ‘altered’ populations of a commonly-used microbubble contrast agent. Dynamic contrast-enhanced (DCE) ultrasound is a non-invasive method of imaging the microvasculature, typically implemented using harmonic imaging. Subharmonic imaging, in which echoes at half the fundamental frequency are detected, detects signals which are generated by the ultrasound contrast agents (UCAs) but not by tissue. However, optimal transmission parameters and furthermore, the optimum acoustic characterisation method have not been established. The subharmonic response of ‘native’ and ‘altered’ UCA, altered through decantation, was investigated at transmit centre frequencies 1.8–5 MHz and pulse lengths 1–8 cycles. The ‘altered’ UCA had reduced polydispersity (1–4 µm: 82% bubble volume), compared to ‘native’ (4–10 µm: 57% bubble volume). A custom-built narrow-band acoustic characterisation system was found to be more appropriate for acoustic characterisation compared to the commonly used broadband pulse-echo approach. Both UCA generated the highest subharmonic signal at pulse length of 3-cycles. The maximum ‘native’ subharmonic signal was generated at a transmit centre frequency of 1.9 MHz, corresponding to a subharmonic at 0.95 MHz. This optimal frequency increased in the ‘altered’ population to 2.3–2.5 MHz, bringing the subharmonic above 1 MHz and hence into a range amenable to clinical abdominal imaging transducers. The use of subharmonic signal detection coupled with a modified UCA size distribution has potential to significantly improve the quantification sensitivity and accuracy of DCE ultrasound imaging.

Clinical Usefulness of the Microbubble Contrast Agent SonoVue in Enhancing the Effects of High-Intensity Focused Ultrasound for the Treatment of Adenomyosis.

To evaluate the clinical usefulness of the microbubble contrast agent SonoVue in enhancing high-intensity focused ultrasound (HIFU) for the treatment of adenomyosis. A total of 102 patients with adenomyosis, assessed from August 2015 to April 2017, were randomly divided into 1-minute (A) and 10-minute (B) groups, respectively. In groups A and B, HIFU started 1 minute and 10 minutes, respectively, after SonoVue injection. All patients underwent a magnetic resonance imaging scan before and after HIFU treatment. The occurrence rates of massive gray scale change, nonperfused volume, and fractional ablation were similar in both groups (P > .05). Meanwhile, sonication time to massive gray scale change was reduced in group A compared with group B (P < .05). In addition, mean power, total energy, and energy efficiency factor were lower in group A than group B (all P < .05). The incidence rates of most perioperative and all postoperative adverse events were similar in both groups (P > .05). The incidence rates of pain in the treated region, leg pain, and sciatic or buttock pain during HIFU were substantially lower in group A than group B (P < .05). Overall, starting HIFU sonication at 1 minute after SonoVue injection enhances HIFU ablation by cavitation and heating and is safe. Early massive gray scale change, lower total energy, and reduced mean power are potential safety factors.

Safety of Sulfur Hexafluoride Microbubbles in Sonography of Abdominal and Superficial Organs: Retrospective Analysis of 30,222 Cases.

The purpose of this study was to investigate the safety of the sulfur hexafluoride microbubble contrast agent SonoVue (Bracco SpA, Milan, Italy) and to implement precautions with the intent of further improving the safety of this contrast agent. A total of 30,222 patients undergoing contrast-enhanced sonography of abdominal and superficial organs in our hospital from January 2005 to December 2014 were retrospectively investigated. SonoVue was used as the ultrasound contrast agent. The symptoms and treatments of adverse reactions occurring during the contrast-enhanced sonographic examinations were reviewed and analyzed. No patient died as a result of any adverse reaction. Six patients (0.020%) had adverse reactions of varying degrees, including 2 patients (0.007%) who had signs of early anaphylactic shock (chest tightness, palpitations, sweating, and rapid and weak pulse, followed by cyanosis, a disappearing pulse, and a drop in blood pressure) that improved after active rescue. The remaining 4 patients developed the following: redness and a rash on the arm above the injection site, nasal bleeding and nausea, nausea and vomiting, and back pain with numbness of the lips and limbs. Symptoms in these 4 patients self-resolved after a period of rest. Contrast-enhanced sonography with sulfur hexafluoride microbubbles had good clinical safety, but rare adverse reactions were observed. A comprehensive emergency plan and rescue measures for adverse reactions should be prepared and made available to minimize the occurrence of negative clinical outcomes.

Accuracy and reliability of microbubble ultrasound measurements for the non‐invasive assessment of hepatic fibrosis in chronic hepatitis C

Contrast-enhanced ultrasound can be used to assess liver disease severity non-invasively by observing intra- and extrahepatic hemodynamic changes. Transit times are calculated to include intra- and extrahepatic components (hepatic vein transit time, HVTT) or the intrahepatic component (hepatic transit time, HTT), but these have not been compared directly. We aimed to compare diagnostic accuracy of HVTT and HTT in gauging the severity of chronic hepatitis C (CHC) and to assess inter- and intra-observer reliability. Recorded ultrasound scans performed on 75 patients with biopsy-staged CHC, using the microbubble contrast agent Sonovue were analyzed. Diagnostic accuracy of HTT and HVTT for diagnosis of cirrhosis was 0.78 and 0.71 (P = 0.24). Diagnostic accuracy of HTT and HVTT for diagnosis of fibrosis stage >2 was 0.76 and 0.72 (P = 0.23). Negative predictive value for cirrhosis using this cut-off was high for both techniques (HVTT, 88%; HTT, 92%), suggesting utility for exclusion of cirrhosis. Inter-observer reliability for HTT and HVTT were 0.92 and 0.94, respectively. Intra-observer reliability for HTT and HVTT were 0.98 and 0.99. In this cohort, reliability exceeded 90% while diagnostic accuracy was in keeping with previous studies of microbubble transit time analysis. Despite higher numerical diagnostic accuracy for HTT, no significant difference was demonstrated between the techniques, suggesting that both methods can be used reliably.

Can contrast‐enhanced sonography distinguish benign from malignant breast masses?

We investigated whether microvascular enhancement on contrast-enhanced sonographic (CEUS) imaging can aid in distinguishing between benign and malignant lesions and correlated these findings with histopathological findings. Fifteen patients with a palpable breast mass were recruited. Following informed consent, 4.8 mL of the microbubble contrast agent SonoVue was injected intravenously. Digital video clips of lesion enhancement were obtained and reviewed by a consultant radiologist who scored each lesion on the following characteristics: homogeneous versus heterogeneous enhancement, the presence or absence of focal defects, well- versus ill-defined margins and vascular morphology score (VMS). Histologically there were 7 malignant and 8 benign lesions. The calculated sensitivity for CEUS in the diagnosis of malignancy was 100%, with a 37.5% specificity. There was no statistically significant difference in overall mean VMS between the malignant and benign lesions. The results of our study have not shown any additional benefit in the use of CEUS over conventional triple assessment. The positive trend seen in the higher mean VMS for the malignant tumors needs further investigation with a larger cohort of patients.

Enhancing effects of microbubble contrast agent of different dosage on high-intensity focused ultrasound ablation in goat liver in vivo

Objective To investigate the enhancing effect of microbubble contrast agent SonoVue of different dosage on high-intensity focused ultrasound (HIFU) ablation in goat livers in vivo. Methods Twenty goats were divided into 4 groups randomly. Animals in group 1,2 and 3 were bolus-injected of 0.01 ml/kg,0. 03 ml/kg and 0.05 ml/kg of SonoVue intravenously before HIFU exposure, respectively,and those in group 4 were not given injections as control. After injection 20s, the livers were ablated using HIFU performed in the manner of a single dot set by a computer system using a clinical device. The frequency of HIFU was 0.8 MHz,the intensity of HIFU was 19 100 W/cm2 ,the distance from skin to the target liver tissue was 30 mm,the exposure time was set at 15 s for all animals in the four groups. All animals were euthanized 7 days after HIFU, volumes of coagulated necrosis were measured. Pathological examinations were performed to analysis the exposure regions. Results Under the same parameters of exposure, coagulated volumes in group 1,2 and 3 were larger than those in group 4, the difference was significant (P < 0.05),and the coagulated volumes increased gradually with the dosage of SonoVue increasing from group 1 to group 3, the difference was significant (P<0.05). Pathological examinations confirmed that there were no residual unaffected tissues within the exposed volume. Two remarkable changes were observed in one goat in group 37 days after HIFU:the surrounding adjacent tissue outside the reactive zone necrotized and the skin were destroyed. Conclusions The enhancing effects of microbubble contrast agent in HIFU ablation is related with the dosage of the microbubble contrast agent SonoVue. The higher the SonoVue dosage,the larger the volume destroy in the target tissue. Key words: Ultrasonography, Ultrasound, high-intensity focused ; Microbubbles, Liver

Nierenzellkarzinome zeigen kein typisches Perfusionsverhalten in der kontrastverstärkten Sonografie

Grayscale ultrasound has improved the outcome of renal cell cancer (RCC), since most significant RCCs are discovered coincidently during routine abdominal ultrasound examinations. The CT scan is currently the method of choice for further evaluation. The therapeutic approach depends on the results of the CT scan. The purpose of this study was to evaluate whether RCCs would show typical vascularization patterns in contrast-enhanced ultrasonography (CEUS). We examined 30 patients with solid renal tumors before surgery with CEUS using the microbubble contrast agent SonoVue (Bracco, Italy). All patients had suspected malignant lesions on a CT scan. The examination was performed with an Acuson Sequoia (Siemens, Erlangen, Germany) with a low mechanical index (low MI) using the contrast agent imaging method "contrast pulsed sequencing" (CPS). We looked at the vascularization in the early phase (< 30 s) and the late phase (60 - 120 s). These findings were compared to the histopathological results. 25 (83 %) had an RCC, and two (7 %) patients showed an urothelial carcinoma. Benign tumors were diagnosed in three (10 %) patients. All of them were oncocytomas. In grayscale ultrasound 52 % of the RCCs were hypoechoic, 36 % isoechoic, and 12 % hyperechoic. After the application of the contrast agent, all RCCs showed a chaotic vascularization pattern. In the early phase (< 30 s), 12 tumors showed hyperperfusion, three showed isoperfusion, and nine showed hypoperfusion. During the late phase (60 - 120 s), five tumors showed hyperperfusion, nine showed isoperfusion, and ten showed hypoperfusion. One small cystic tumor did not indicate contrast enhancement at any time. In our study RCC showed chaotic vascularization in CEUS without typical vascularization patterns.

Real-time contrast-enhanced specific ultrasound in staging and follow-up of splenic lymphomas

From January 2003 to April 2005 we studied 25 lymphoma patients (10 with HD, 4 with low-grade NHL, 6 with high-grade NHL and 5 with chronic lymphatic leukaemia; 14 men, 11 women, age range 28-79 years). After a baseline US study we rapidly injected 4.8 mL of the second-generation microbubble contrast agent SonoVue (Bracco, Italy). Contrast enhanced studies were carried out with the contrast-specific software named Contrast Tuned Imaging (Esaote, Italy) using a continuous, harmonic acquisition and a low acoustic pressure. The CS-US findings were correlated with results of standard tools, including CT, MRI, US follow up. CS-US revealed correctly 47 out of the 52 lesions identified by CT scan, in the absence of false positive findings (sensitivity = 90%; Specificity = 100%, in comparison to CT scan). Complete concordance in evaluating the lesion extension of the CS-US in respect to CT was 88%, while underestimate occurred in 9% and overestimate in 3% of cases. On the contrary, basic sonography defined correctly the dimensional alteration in 52% of the cases, underestimated in 35% and overestimated in 13%, thus showing significantly lower accuracy (chi-square = 30.0, p < 0.001). In our experience, CS-US was superior to conventional sonography even from a qualitative point of view.

Benefit of Echocontrast-Enhanced Transcranial Arterial Color-Coded Duplex Ultrasound

Objectives: Proper assessment of the intracranial arteries by transcranial color-coded duplex sonography (TCCD) is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all. Material and Methods:We investigated 67 temporal windows of 47 patients with insufficient native transtemporal insonation conditions before and after the application of the second-generation (gas-filled) microbubble contrast agent Sonovue^® (in 20 patients out of these 47, both temporal windows were insufficient, in the remaining 27 only one side). Results: As compared to the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (p < 0.0001) and for longer lumen segments to be displayed on color mode (p < 0.0001). With the help of contrast medium, flow velocity in the middle cerebral artery could be measured through 65 windows as compared to only 26 windows before contrast was applied (p < 0.0001). Conclusions: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful.