To evaluate diagnostic combinations of imaging modalities and contrast agents for vesicoureteral reflux (VUR) in children.

Studies were retrieved in PubMed, EMBASE, Cochrane Library, Web of science, and China National Knowledge Infrastructure (CNKI) until March 16, 2023. We used bivariate random-effects model and a frequentist model for meta-analysis. Surface under the cumulative ranking curve (SUCRA) was used to rank ceVUS protocols.

19 studies identified 4 diagnostic combinations. Contrast-harmonic ultrasound with SonoVue® (CHSV) had significantly lower sensitivity, specificity, and diagnostic accuracy than VCUG, although its negative predictive value was higher than VCUG. Contrast-harmonic ultrasound with Optison™ (CHOS) was comparable to VCUG across all diagnostic measures. SUCRA analysis favored CHOS, with probabilities of being the best for SEN, SPE, PPV, NPV, DOR, and DA at 50.9%, 16.6%, 42.6%, 57.4%, 36.2%, and 20.4%, respectively.

Harmonic VUS with Optison™ may be the optimal protocol for VUR detection in children.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42023424510, identifier (CRD42023424510).

The goal of this study was to evaluate the performance of different commercial ultrasound contrast microbubbles (MBs) when measuring bladder phantom pressure with sub-harmonic-aided pressure estimation (SHAPE) methodology. We hypothesized that SHAPE performance is dependent on MB formulation. This study aimed to advance the SHAPE application for bladder pressure measurements in humans.

Using a previously designed and built bladder phantom, we tested four different commercial agents: Definity, Lumason, Sonazoid and Optison. A standard clinical cystometrogram (CMG) system was used to infuse a MB-saline mixture into the bladder phantom to measure pressure. Ultrasound imaging was performed using the GE Healthcare LOGIQ E10 scanner.

All agents showed a predicted inverse linear relationship between change in pressure and SHAPE signal. However, they differ from each other in terms of stability, linear correlation, sensitivity to pressure and error. Generally, Definity and Lumason showed the highest performance during the SHAPE-based bladder phantom pressure assessments.

Our results show that the SHAPE signal decreases as bladder phantom pressures increases, regardless of the agent or CMG phase, suggesting the possibility of using SHAPE for measuring bladder pressure without a catheter. However, the efficacy of SHAPE in measuring pressure varies by MB formulation. These observations support using Lumason and Definity in a human subject feasibility study as we advance toward a catheter-free solution for measuring voiding bladder pressure via SHAPE.

Contrast-enhanced ultrasound of the urinary tract and bladder (ceVUS) is an alternative examination method to micturition cysturethrography (MCU/VCUG) for suspected vesicoureteral reflux (VUR) that is increasing in practice. The purpose of this review is to present the current value of ceVUS in the diagnosis.

A systematic literature search was performed using the keywords "vesicoureteral reflux", "ceVUS", "VCUG" of the databases MEDLINE and Cochrane Library as well as a review of current German, European, and American guidelines on this topic. In addition, recommendations for action in clinical practice were developed.

ceVUS is a quick-to-learn examination method that is equivalent to VCUG for the diagnosis of vesicoureteral reflux and should be used as the diagnostic method of first choice when available given the absence of radiation exposure.

· Like VCUG, ceVUS is the diagnostic method of first choice in suspected vesicoureteral reflux and should be used preferentially given the absence of radiation exposure.. · Especially in comparison to the alternative VCUG, ceVUS is a quick-to-learn examination method.. · ceVUS can also be used to diagnose other pathologies of the lower urinary tract..

· Conen P, Thiemann J, Stredele R et al. Value of contrast-enhanced sonography in the diagnosis of vesicoureteral reflux. Fortschr Röntgenstr 2024; 196: 1022 - 1028.

Vesicoureteral reflux (VUR) is a common congenital anomaly of the urinary tract that can present with collecting system dilation or as a febrile infection. VUR can lead to permanent renal sequelae requiring surgery but can also spontaneously resolve without complication. Therefore, recognizing patient populations who warrant imaging for screening, confirmation, or ongoing surveillance for VUR is important, as is avoiding overdiagnosis. In the appropriate patient populations, an accurate diagnosis of VUR allows early treatment and prevention of pyelonephritis and scarring. Various imaging modalities are available to diagnose and grade VUR, including voiding cystourethrography, radionucleotide cystography, and contrast-enhanced voiding urosonography (ceVUS). The objective of this article is to summarize the current understanding of VUR diagnosis and management and to discuss these imaging modalities' strengths and pitfalls. Considerations include indications for VUR imaging, patient preparation, conduct of the examination, issues related to radiologic reporting, and cost-effectiveness. An emphasis is placed on ceVUS, which is the most recently introduced of the three imaging modalities and is receiving growing support among pediatric radiologists.

Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1-11% when using voiding cystourethrography (VCUG), while 11.9-61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.

We mainly aimed to perform a narrative review of clinical applications of the three intracavitary contrast-enhanced ultrasonography (CEUS) including contrast-enhanced voiding urosonography (ceVUS), contrast-enhanced retrograde urethrosonography (ceRUG), and contrast-enhanced genitosonography (ceGS) in pediatric lower genitourinary anomalies.

A literature search in the PubMed and Web of Science databases was conducted up to 1 July 2022 on all studies published in English using the search terms "contrast-enhanced voiding urosonography", "contrast-enhanced retrograde urethrosonography", and "contrast-enhanced genitosonography". Trials were limited to pediatric subjects (ages ≤18 years) with no time restrictions. The inclusion criteria were studies on ceVUS, ceRUG, and ceGS to evaluate pediatric lower genitourinary anomalies. Two independent authors summarized the included articles.

Finally, a total of 48 original articles and 6 case reports or case series were included, of which 50 (93%) were only relevant to ceVUS, 3 (5%) articles involved ceGS, while only one (2%) article involved ceRUG, and 87% of the applications of ceVUS were focused on vesicoureteral reflux (VUR). We also searched 24 related reviews, of which 20 involved ceVUS in diagnosing VUR and 4 involved ceRUG and ceGS for other lower genitourinary anomalies.

Intracavitary CEUS including ceVUS, ceRUG, and ceGS in pediatrics has many advantages over other radiological examinations in diagnosing lower genitourinary anomalies. Although ceVUS is widely used in detecting VUR, ceRUG and ceGS have also become promising techniques for evaluating the urethral pathologies and urogenital sinus.

Ultrasound's versatility and ease of use has expanded its application in many clinical settings. Technological advancements with contrast-enhanced ultrasound (CEUS) have allowed high quality imaging similar to CT or MRI with lower risk of contrast toxicity and radiation exposure. In this review article we examine the development of CEUS and its vast applications in the field of urology.

A PubMed literature search was performed using keywords: contrast enhanced ultrasound, prostate cancer, renal cancer, and multiparametric ultrasound.

The development of CEUS has improved transrectal ultrasound imaging with increased detection of prostate cancer (PCa). Further enhancements of CEUS such as subharmonic imaging (SHI), flash replenishment imaging (FRI) and contrast ultrasound dispersion imaging (CUDI) allow improved PCa diagnosis. CEUS has also emerged as an important tool in characterizing suspicious renal mass without compromising renal function with contrast imaging.

CEUS has modernized imaging and diagnosis of prostate and renal cancer. Future advancements and utilization of CEUS will allow its expansion into other urological subspecialties.

The diagnostic value of contrast-enhanced voiding urosonography (ceVUS) in the diagnosis of vesicoureteral reflux (VUR) is still a subject of dispute.

Assessing the diagnostic value of ceVUS in VUR, performing a systematic review and meta-analysis.

An extensive search on Medline, Embase, Scopus and Web of Science databases was conducted by the end of 2020. The inclusion criteria were studies on the diagnostic value of ceVUS for VUR. Two independent researchers summarized the included articles and the findings were reported as area under the curve (AUC), sensitivity and specificity with a 95% confidence interval (95% CI).

Finally, the data of 36 articles were included in the present meta-analysis (2768 children). The VUS assessment showed that 1297 of the cases were true positives, 3661 were true negatives, 398 were false positives and 169 were false negatives. The AUC, sensitivity and specificity of ceVUS with the first-generation contrast agent in the diagnosis of VUR in children and adolescents were obtained as 0.97 (95% CI: 0.95, 0.98), 0.92 (95% CI: 0.86, 0.96) and 0.94 (95% CI: 0.95, 0.98), respectively. Moreover, AUC, sensitivity and specificity of ceVUS with the second-generation contrast agent were 0.97 (95% CI: 0.95, 0.98), 0.93 (95% CI: 0.86, 0.97) and 0.91 (95% CI: 0.86, 0.95).

The findings of the present study showed that diagnostic value of ceVUS with both first-generation and second-generation contrast agents for VUR, is in an excellent range. Although it seems that ceVUS may be applied as a radiation-free alternative to imaging techniques such as VCUG, the presence of 3% of false negatives in this test is a limitation. Since the lack of punctual management of VUR is associated with serious renal complications in children, future studies are recommended to be focused on the evaluation of the Benefit-risk evaluation of ceVUS.

Contrast-enhanced voiding urosonography (ceVUS) is a well-established, sensitive and safe ultrasound (US) modality for detecting and grading vesicoureteral reflux (VUR) and urethral imaging in children. Nearly three decades of remarkable advances in US technology and US contrast agents have refined ceVUS's diagnostic potential. The recent approval of Lumason/SonoVue in the United States, Europe and China for pediatric intravesical applications marked the beginning of a new era for this type of contrast US imaging. Consequently, the use of ceVUS in children has expanded to multiple places around the globe. In the first part of this review article, we describe the current experience in the use of ceVUS for VUR evaluation, with an emphasis on historical background, examination technique, image interpretation and diagnostic accuracy. In the second part, we will present the role of ceVUS for urethral imaging 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.

Vesicoureteral reflux (VUR) represents a common pediatric anomaly in children with an upper urinary tract infection (UTI) and is defined as a retrograde flow of urine from the bladder into the upper urinary tract. There are many diagnostic options available, including voiding cystourethrography (VCUG) and contrasted-enhanced urosonography (ceVUS). ceVUS combines a diagnostic tool with a high sensitivity and specificity which, according to previous study results, was even shown to be superior to VCUG. Nevertheless, despite the recommendation of the EFSUMB, the ceVUS has not found a widespread use in clinical diagnostics in Europe yet.

Between 2016 and 2020, 49 patients with a marked female dominance (n = 37) were included. The youngest patient had an age of 5 months, the oldest patient 60 years. The contrast agent used in ceVUS was SonoVue®, a second-generation blood-pool agent. All examinations were performed and interpreted by a single experienced radiologist (EFSUMB Level 3).

The 49 patients included in the study showed no adverse effects. 51% of patients (n = 26) were referred with the initial diagnosis of suspected VUR, while 49% of patients (n = 23) came for follow-up examination or to rule out recurrence of VUR. The vast majority had at least one febrile urinary tract infection in their recent medical history (n = 45; 91,8%).

ceVUS is an examination method with a low risk profile which represents with its high sensitivity and specificity an excellent diagnostic tool in the evaluation of vesicoureteral reflux, especially in consideration of a generally very young patient cohort.

Vesicoureteral reflux (VUR) is a pathological condition contradistinguished by monolateral or bilateral retrograde flow of urine from the bladder to the ureter and to the kidney. If not properly recognized and treated, VUR can potentially be associated to several complications such as recurrent infections and possible secondary scars with Chronic Kidney Disease (CKD). Furthermore, it represents an important risk factor for nephrovascular hypertension. During the last 20 years, the diagnostic approach to this entity has passed through several, drastic changes: indeed, since its introduction in 1994 contrast-enhanced voiding urosonography (ceVUS) has gradually accompanied the voiding cystourethrography (VCUG) as alternative imaging technique for the diagnosis and staging of VUR. Despite a large number of papers has strongly encouraged its use in clinical practice, due to the lack of ionizing radiations and its high sensitivity rate, to date almost all the guidelines only include the VCUG for VUR diagnosis. The introduction of technologically advanced US software and the approval of the intravesical administration of ultrasound contrast agents by the Food and Drug Administration (FDA) and by the European Medicine Agency (EMA) have to induce the Scientific Community to a deep revaluation of the role of ceVUS in the diagnosis and follow-up of VUR: urosonography might extensively replace VCUG as the reference method, reserving to cystourethrography a role in the most complex anatomic settings for pre-surgical evaluation.