Second-generation Ultrasound Contrast Research Articles

Ultrastable fluorinated copolypeptide nanodroplets of loaded mixed liquids with low vaporization threshold

The expansion of ultrasound molecular imaging applications warrants a reduction in ultrasound contrast agent size and significant advancement in the in vivo stability of shell-stabilized bubbles. The shift from first to second-generation ultrasound contrast agents was marked by an improvement in stability as air was replaced by hydrophobic gases like perfluoropropane and sulfur hexafluoride. Further enhancements may be facilitated by focusing on strategies to retain the encapsulated gas within the ultrasound contrast agent shell despite extreme mechanical deformations. In this study, we developed a novel ultrasound contrast agent with a unique shell structure and a specially-formulated, low-boiling fluorinated liquid interior, resulting in superior stability during repeated and prolonged ultrasound-induced oscillations. Our ultra-stable nanodroplets can withstand sustained in vitro ultrasound exposure with minimal signal attenuation and can induce significant signal enhancement and delay in signal attenuation in the kidney, liver, and tumor tissues during in vivo experiments. Furthermore, encapsulating photosensitizers within these nanodroplets and leveraging photothermal effects could further augment the ultrasound imaging signal and verify its efficacy in tumor therapy. The creation of highly stable nanodroplets opens immense potential to augment the role of ultrasound in molecular imaging, therapy, and drug delivery.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines from the Korean Society of Radiology and the Korean Society of Abdominal Radiology

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology.

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Contrast-enhanced ultrasound: a comprehensive review of safety in children.

Contrast-enhanced ultrasound (CEUS) has been increasingly used in pediatric radiology practice worldwide. For nearly two decades, CEUS applications have been performed with the off-label use of gas-containing second-generation ultrasound contrast agents (UCAs). Since 2016, the United States Food and Drug Administration (FDA) has approved the UCA Lumason for three pediatric indications: the evaluation of focal liver lesions and echocardiography via intravenous administration and the assessment of vesicoureteral reflux via intravesical application (contrast-enhanced voiding urosonography, ceVUS). Prior to the FDA approval of Lumason, numerous studies with the use of second-generation UCAs had been conducted in adults and children. Comprehensive protocols for clinical safety evaluations have demonstrated the highly favorable safety profile of UCA for intravenous, intravesical and other intracavitary uses. The safety data on CEUS continue to accumulate as this imaging modality is increasingly utilized in clinical settings worldwide. As of August 2021, 57 pediatric-only original research studies encompassing a total of 4,518 children with 4,906 intravenous CEUS examinations had been published. As in adults, there were a few adverse events; the majority of these were non-serious, although very rarely serious anaphylactic reactions were reported. In the published pediatric-only intravenous CEUS studies included in our analysis, the overall incidence rate of serious adverse events was 0.22% (10/4,518) of children and 0.20% (10/4,906) of all CEUS examinations. Non-serious adverse events from the intravenous CEUS were observed in 1.20% (54/4,518) of children and 1.10% (54/4,906) of CEUS examinations. During the same time period, 31 studies with the intravesical use of UCA were conducted in 12,362 children. A few non-serious adverse events were encountered (0.31%; 38/12,362), but these were most likely attributable to the bladder catheterization rather than the UCA. Other developing clinical applications of UCA in children, including intracavitary and intralymphatic, are ongoing. To date, no serious adverse events have been reported with these applications. This article reviews the existing pediatric CEUS literature and provides an overview of safety-related information reported from UCA uses in children.

Contrast-enhanced voiding urosonography in the diagnosis of intrarenal reflux.

Although contrast-enhanced urosonography (ceVUS) has shown capable diagnostic accuracy for the diagnosis of vesicoureteral reflux (VUR) in children, the ability of ceVUS to detect intrarenal reflux (IRR) is considered limited. The purpose of our study is to assess the ability of ceVUS to detect IRR as well as its association with age, gender, and the grade of VUR. This study included 5153 children who were referred to our clinic for ceVUS. All children underwent sonographic examinations, which were performed on a LOGIQ S8 machine equipped with dedicated software for contrast-enhanced studies with harmonic imaging. Standard ultrasound of the urinary tract was followed by bladder catheterisation and instillation of physiological normal saline and the US contrast medium (SonoVue®, Bracco). VUR was diagnosed by ceVUS in 1959 out of 5153 children (38%), of whom IRR was found in 233 of 1959 children (11.9%). A total of 285 ureteral units showing IRR were found. High grades of VUR (IV + V) with IRR were found in a total of 235 of 285 (82.81%) renal units. Bilateral IRR was found in 53 patients, usually with a high-grade VUR on both sides. Most children had VUR grade IV, predominantly those < 12months. The younger the child, the higher the likelihood of higher-grade VUR (p = 0.02). ceVUS, combined with harmonic imaging and second-generation ultrasound contrast media, enabled IRR detection in almost 12% of our patients with VUR. IRR is most commonly found in children under 1year of age with VUR grades IV and V.

Contrast-enhanced voiding urosonography for the diagnosis of vesicoureteral reflux and intrarenal reflux: a comparison of diagnostic performance with fluoroscopic voiding cystourethrography.

PurposeThis study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG).MethodsThirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR.ResultsTwenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016).Conclusionce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

The Safety and Effectiveness of Intravenous Contrast-Enhanced Sonography in Chinese Children-A Single Center and Prospective Study in China.

Background and Objective: Intravenous contrast-enhanced ultrasound (CEUS), using the second-generation ultrasound contrast agent SonoVue®, has been widely used in adults. In 2016, it was approved for pediatric applications by the American Food and Drug Administration (FDA). However, it has not been approved by the Chinese Food and Drug Administration (CFDA). The objective of the study was to evaluate the safety and effectiveness of CEUS in children prospectively at a single center in China. Methods: A total of 312 cases of Chinese children were enrolled in clinical trials. Contrast agent was given intravenously with two different doses, including 2.4 ml/time and 0.03 ml/kg. All CEUS was performed for evaluating adverse effect and the diagnostic accuracy compared with the pathology and enhanced CT. Results: All 312 subjects underwent CEUS successfully. The dose of contrast agent for CEUS was 2.4 ml between November 2015 and June 2016, which was modified to 0.03 ml/kg between July 2016 and April 2019, according to the recommendation of the FDA. With the two different doses of the contrast agent, the heart rate, respiration rate, oxygen saturation, and blood pressure of the participants had no statistically significant difference (P > 0.05) before and after administration. The blood pressure had been significantly decreased in participants who received combined anesthetic administration. Following 600 intravenous injections of the CEUS, there were three cases of transient rash and three cases of hypotension (n = 6, 1.92%). The six recovered quickly after receiving intravenous methylprednisolone and epinephrine. Most of the studies were performed for evaluating renal microcirculation and assisting renal biopsy (192/312 [61.5%]), which together had a 98.9% effectiveness in the identification of pathology in the specimens. Some studies were conducted to identify a mass in the liver, retroperitoneum, abdominal cavity, kidneys, testicles, thyroid, and so on (99/312 [31.4%]), which had a 97.6% accuracy. The other studies were conducted to identify trauma, vascular malformation, infection, hemorrhage, and so on (21/312 [6.73%]), which had a similar accuracy to enhanced CT. Conclusion: The adverse effects of CEUS in children are similar to that in adults. The results indicate that it is safe to use SonoVue® for CEUS in pediatric patients.

Stress Echocardiography: An Update

Stress echocardiography (SE) is an established technique for the assessment of extent and severity of coronary artery disease. The combination of echocardiography with a physical, pharmacological or electrical stress allows to detect myocardial ischemia with an excellent accuracy. A transient worsening of regional function during stress is the hallmark of inducible ischemia. In recent years, SE has become an established method for the assessment of a wide spectrum of challenging clinical conditions, including systolic or diastolic heart failure, non-ischaemic cardiomyopathy, valvular heart disease, pulmonary hypertension (PH), athletes’ hearts, congenital heart disease (CHD) and heart transplantation. Advantages of SE include the ubiquitous availability of echocardiography, lack of ionising radiation, choice of physiological or pharmacological stressors, good diagnostic accuracy and robust supporting evidence base. SE has evolved significantly as a technique over the past three decades and has benefitted considerably from improvements in overall image quality (superior resolution), machine technology (e.g. digital cine-loop acquisition and side-by-side image display) and development of second-generation ultrasound contrast agents that have improved reader confidence and diagnostic accuracy. SE provides similar diagnostic and prognostic accuracy as radionuclide stress perfusion imaging or magnetic resonance, but at a substantially lower cost, without environmental impact, and with no biohazards for the patient and the physician. A paradigm shift will occur when from a highly expertise qualitative reading SE will move to a quantitative approach that would make it easier also for less skilled readers. Technological premises are there at hand but they have not reached a full-blown status to be used on a routine clinical basis. Society recommendations and guidelines are mostly based on consensus and level of evidence C. The gap of knowledge should be filled with prospective large scale studies to support evidence-based treatment strategies. The purpose of this article is to review the breadth of SE in contemporary clinical cardiology.University Heart Journal Vol. 14, No. 1, Jan 2018; 31-37

Applications of contrast-enhanced ultrasound in the pediatric abdomen.

Contrast-enhanced ultrasound (CEUS) is a radiation-free, safe, and in specific clinical settings, highly sensitive imaging modality. Over the recent decades, there is cumulating experience and a large volume of published safety and efficacy data on pediatric CEUS applications. Many of these applications have been directly translated from adults, while others are unique to the pediatric population. The most frequently reported intravenous abdominal applications of CEUS in children are the characterization of focal liver lesions, monitoring of solid abdominal tumor response to treatment, and the evaluation of intra-abdominal parenchymal injuries in selected cases of blunt abdominal trauma. The intravesical CEUS application, namely contrast-enhanced voiding urosonography (ceVUS), is a well-established, pediatric-specific imaging technique entailing the intravesical administration of ultrasound contrast agents for detection and grading of vesicoureteral reflux. In Europe, all pediatric CEUS applications remain off-label. In 2016, the United States Food and Drug Administration (FDA) approved the most commonly used worldwide second-generation ultrasound contrast SonoVue®/Lumason® for pediatric liver and intravesical applications, giving new impetus to pediatric CEUS worldwide.

Voiding Urosonography with Second-Generation Ultrasound Contrast Agent for Diagnosis of Vesicoureteric Reflux: First Local Pilot Study

BACKGROUND:Vesicoureteric reflux (VUR) is an important association of paediatric urinary tract infection (UTI) found in 30-50% of all children presenting with first UTI. Contrast-enhanced voiding ultrasonography (ceVUS) has become an important radiation-free method for VUR detection in children. Its sensitivity in detecting VUR has greatly improved due to the development of the contrast-specific ultrasound techniques and the introduction of the second-generation ultrasound contrast agent, superseding the diagnostic accuracy of standard radiological procedures.AIM:This article aimed to summarise the current literature and discuss the first local pilot study performed in our institution on detection of vesicoureteric reflux by contrast-enhanced voiding ultrasonography with second- generation agent (SonoVue, Bracco, Italy).MATERIAL AND METHODS:Retrospective review of the first 31 ceVUS (24 girls, 7 boys) was presented. Age range was 2 months to 18 years (mean = 6.4 ± 4.9).RESULTS:All examinations were well tolerated without any adverse incident. VUR was shown in 20 (64.5%) children in 32/62 (51.6) nephroureteral units (NUUs). In 18 NUUs, VUR was grade II/V, in 11 Grade III/V and in 3 grade IV/V, respectively. Urethra was shown in 19/31 children and in all boys, without pathological finding. In two girls spinning top urethra has been detected. Subsequent urodynamic studies revealed functional bladder problem in both.CONCLUSIONS:Contrast-enhanced voiding urosonography using intravesical second generation ultrasound contrast agent could be recommend as a valid alternative diagnostic modality for detecting vesicoureteral reflux and evaluation of the distal urinary tract in children, based on its radiation-free, highly efficacious, reliable, and safe characteristics.

Applications of contrast-enhanced harmonic endoscopic ultrasound on biliary, focal liver lesions and vascular diseases

Over the last decade, the clinical applications of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) have increased steadily. The development of second-generation ultrasound contrast agents has allowed superior visualization of the microvasculature and tissue perfusion of the target lesion. This methodology has proven useful in the differential diagnosis of solid pancreatic masses and lymph nodes. In addition, the applicability of CH-EUS has expanded to nonpancreas structures such as biliary, focal liver lesions, and vascular disease. This article focuses primarily on the novel applications of CH-EUS in biliary tract and visceral vascular diseases.

339 Comparison of voiding cystourethrography and urosonography with second-generation contrast agents in simultaneous prospective study

BackgroundThe invasiveness and exposure to radiation in voiding cystourethrography led to the introduction of alternative methods of diagnosis of vesicoureteral reflux, including contrast enhanced voiding urosonography. While there is a limited number of studies comparing these methods using new generation ultrasound contrast agents, none of them compared both methods simultaneously. This study is aimed at assessing agreement between contrast enhanced voiding urosonography with second-generation ultrasound contrast agents and voiding cystourethrography.MethodsFrom April 2013 to May 2014, 83 children (37 female and 46 male), mean age 3.5 years, age range from 1 month to 17.5 years, underwent prospective simultaneous assessment by contrast enhanced voiding urosonography and voiding cystourethrography, with a total of 166 uretero-renal units evaluated.ResultsThe sensitivity of voiding cystourethrography and contrast enhanced voiding urosonography were comparable, amounting to 88%, however, neither reached 100% for the entire studied population. The negative predictive value of voiding urosonography and voiding cystourethrography was 97%, and there was no difference between both methods.ConclusionVoiding cystourethrography and contrast enhanced voiding urosonography are comparable methods in diagnosis of vesicoureteral reflux, and can be performed alternatively. However, some limitations of contrast enhanced voiding urosonography must be remembered.

Hepatic vein transit time of second-generation ultrasound contrast agent: new tool in the assessment of portal hypertension

It has been demonstrated that Doppler waveform of the hepatic vein (normally triphasic) is transformed into a biphasic or monophasic waveform in cirrhotic patients. The compressive mechanism of liver tissue has been considered up till now the cause of this change. Moreover, cirrhotics show, after USCA injection, a much earlier HVTT due to intrahepatic shunts. Our aim was to prospectively evaluate the correlation between Doppler pattern of hepatic vein and HVTT of a second-generation USCA; we also correlated HVTT with the most common indexes of portal hypertension. We enrolled 38 participants: 33 cirrhotics and 5 healthy controls. Doppler shift signals were obtained from the right hepatic vein. To characterize the hepatic vein pattern, we used the hepatic vein waveform index (HVWI). This index becomes >1 with the appearance of the triphasic waveform. We recorded a clip from 20s before to 2min after a peripheral intravenous bolus injection of 2.4ml of USCA (sulfur hexafluoride).The time employed by USCA to cross the liver from the hepatic artery and portal vein to the hepatic vein was defined as HA-HVTT and PV-HVTT, respectively. Cirrhotics with low HVWI showed an earlier transit time; participants with higher HVWI had a longer transit time (p<0.001). HVTT was earlier as MELD, Child-Pugh score and spleen diameter increased. Patients with ascites and varices of large size had significantly shorter transit times. Abnormal hepatic vein Doppler waveform in cirrhotic patients could be due to intrahepatic shunts. HVTT could be useful in the non-invasive evaluation of portal hypertension.

Intraoperative Navigated Angiosonography for Skull Base Tumor Surgery

-BACKGROUND: One of the main challenges during skull base tumor surgery is identifying the relationships between the lesion and the principal intracranial vessels. To this end, neuronavigation systems based on preoperative imaging lack accuracy because of brain shift and brain deformation. Intraoperative navigated B-mode ultrasonography is useful in defining the extent of brain tumor. Doppler imaging adds information regarding flow entity in neighboring vessels. Second-generation ultrasound contrast agents improve the signal-to-noise ratio of Bmode imaging and permit the study of the vessel’s course, blood flow, and perfusion characteristics of focal lesions. We report our experience using intraoperative navigated contrast-enhanced ultrasound to perform a navigated angiosonography (N-ASG) for the visualization of vessels in a series of 18 skull base tumors.

Off-Label Use of Ultrasound Contrast Agents for Intravenous Applications in Children: Analysis of the Existing Literature.

The purpose of this study was to collect and analyze the published data related to intravenous (IV) use of ultrasound (US) contrast agents in children. We searched the literature to collect all of the published studies reporting the IV administration of a second-generation US contrast agent in children. We analyzed 9 case series and 5 case reports, as well as 5 individual cases, of pediatric contrast-enhanced US use reported in a study group that also included adults. We found that 502 children underwent contrast-enhanced US examinations (mean age, 9.7 years; range, 1 day-18 years). Most patients (89%) were injected with the sulfur hexafluoride contrast agent SonoVue (Bracco SpA, Milan, Italy). The mean dose used was 1.5 mL (range, 0.1-9.6 mL). Only 10 patients (2%) had adverse reactions related to the contrast agent administration: 1 life-threatening anaphylactic shock and 9 mild transitory adverse effects. We additionally found 38 papers in which the study groups included at least 1 child; thus, we obtained a total of 540 reported cases of off-label use of IV US contrast agents in children. The most frequent target organ was the liver, and most indications were related to space-occupying lesion characterization and abdominal evaluations after blunt trauma. Some studies also evaluated the diagnostic performance of contrast-enhanced US in different clinical scenarios and found very good accuracy. Concordance between contrast-enhanced US imaging and the respective reference-standard imaging methods ranged between 83% and 100% in different studies. Our results support the idea that the IV use of US contrast agents in children is safe, feasible, diagnostically robust, and effective.

Intraoperative Navigated Angiosonography for Skull Base Tumor Surgery

One of the main challenges during skull base tumor surgery is identifying the relationships between the lesion and the principal intracranial vessels. To this end, neuronavigation systems based on preoperative imaging lack accuracy because of brain shift and brain deformation. Intraoperative navigated B-mode ultrasonography is useful in defining the extent of brain tumor. Doppler imaging adds information regarding flow entity in neighboring vessels. Second-generation ultrasound contrast agents improve the signal-to-noise ratio of B-mode imaging and permit the study of the vessel's course, blood flow, and perfusion characteristics of focal lesions. We report our experience using intraoperative navigated contrast-enhanced ultrasound to perform a navigated angiosonography (N-ASG) for the visualization of vessels in a series of 18 skull base tumors. We performed N-ASG in a series of 18 skull base tumors (10 meningiomas, 3 craniopharyngiomas, 2 giant pituitary adenomas, 1 posterior fossa epidermoid, 2 dermoid cysts). N-ASG was obtained after craniotomy before resecting each lesion and during tumor removal, after intravenous injection of ultrasound contrast agent. In all 18 cases, major vessels and their branches were simultaneously identified (both high and low flow) using N-ASG, which allowed to visualize the whole length of each vessels. N-ASG was also useful in highlighting the lesion, compared with standard B-mode imaging, and showing its perfusion patterns. N-ASG can be applied to skull base tumor surgery, providing helpful information about the relationship between principal intracranial vessels and tumors. This technique could be of assistance in approaching the tumor and avoiding vascular damages.

Contrast-enhanced voiding urosonography: in vitro evaluation of a second-generation ultrasound contrast agent for in vivo optimization.

Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0.21 for the 9MHz and 0.39 for the 12MHz (P < 0.01) transducers. The 0.5% US contrast agent volume to bladder filling was the most optimal. At this concentration, the mean time to visualize homogenous contrast was 2min and destruction of approximately half of the microbubbles in the field of view occurred in 7.8min using the 9-MHz transducer. During contrast infusion, the contrast dose needed to be reduced to 0.12% for maintenance of optimal visualization of microbubbles. There was no deleterious effect on the visualization of contrast in the presence of urine or radiographic contrast agent. Infusion of the US contrast agent speeded visualization of homogeneous enhancement compared with injection. Time outside refrigeration did not affect contrast performance. Transducer mechanical index settings need to be optimized. A very low dose of the US contrast agent Optison® will suffice for intravesical application, i.e. 0.12% to 0.50% of the bladder filling volume. The presence of urine or radiographic contrast agent did not compromise contrast visualization. The best mode of administration is the infusion method due to fast homogenous distribution at the lowest dose of 0.12%. Leaving the US contrast agent outside the refrigerator for an hour does not affect the microbubbles.

Contrast-enhanced harmonic endoscopic ultrasonography for pancreatobiliary diseases.

The combination of second-generation ultrasound contrast agents and an endoscopic ultrasonography (EUS) system with a broad-band transducer has allowed contrast-enhanced harmonic imaging in the field of EUS. In contrast-enhanced harmonic EUS (CH-EUS), diffuse homogeneous enhancement is obtained in normal parenchyma of the pancreas. The bile duct and pancreatic duct are depicted as non-enhanced ductal structures with strong contrast in comparison to the surrounding parenchyma. CH-EUS identifies pancreatic adenocarcinomas as solid lesions exhibiting hypo-enhancement with a sensitivity and specificity of 88-96% and 88-94%, respectively. In particular, 80-100% of false-negative cases in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are correctly classified by CH-EUS, suggesting CH-EUS complements EUS-FNA. Moreover, CH-EUS improves depiction of some subtle lesions in conventional EUS, thus facilitating EUS-FNA. For quantitative perfusion analysis, a time-intensity curve (TIC) for the region of interest can be generated during CH-EUS. The maximum intensity gain and the echo intensity reduction rate from the peak at 1 min obtained by TIC can be used for differentiation of pancreatic adenocarcinoma from other tumors. CH-EUS is also useful for differentiation of invasive intraductal papillary mucinous neoplasms (IPMN) from non-invasive IPMN, identification of malignant lesions in the gallbladder, and T- and N-staging of pancreatobiliary tumors.

Safety of Intravenous Application of Second-Generation Ultrasound Contrast Agent in Children: Prospective Analysis

The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile.

Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma.

Background/AimsThe predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE.MethodsSeventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue®, Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%≤enhancing tumor<50%; 3, 50%≤enhancing tumor<75%; and 4, enhancing tumor≥75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor.ResultsThe median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (≤5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively).ConclusionsThe presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS.