The Learning Curve of Contrast-Enhanced “Microbubble” Urosonography – A Validation Study

Introduction Vesicoureteral reflux (VUR) is a common pediatric urologic condition associated with urinary tract infection and pyelonephritis. It can be diagnosed via fluoroscopic voiding cystourethrogram (VCUG) and, more recently, contrast-enhanced voiding ultrasonography (ceVUS), which does not expose the patient to ionizing radiation. Voiding urosonography contrast agents used for the diagnosis of VUR have been widely available in Europe but were approved by the Food and Drug Administration for use in the United States only in 2016. Objective The objective was to optimize a protocol and compare the diagnostic performance of ceVUS to fluoroscopic VCUG in an academic medical center naive to previous use of contrast-enhanced voiding urosonography. Study design Thirty-nine patients referred for clinically indicated evaluation of VUR were enrolled between September 2016 and March 2017. Patients underwent contrast-enhanced ultrasonography with prediluted Lumason and under the same catheterization underwent fluoroscopic VCUG. Comparative grading was performed by pediatric radiologists on-site at the time of examination. Results Reflux was observed in 16 of 39 patients (20 of 64 renal units) ranging from grades 1 through 5. VCUG and ceVUS were concordant for detecting reflux in 10 of 39 patients (14 of 84 renal units) and excluding reflux in 23 of 39 patients (64 of 84 renal units) (Fig. 1). Using contrast enhanced voiding urosonography, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that was not found on fluoroscopy. Using fluoroscopy, 1 of 20 renal units had high-grade and 2 of 20 renal units had low-grade reflux that had not been found on ceVUS. Two of 20 renal units were upgraded from low-grade on ceVUS to high-grade on fluoroscopy. This corresponds to a Cohen's kappa of 0.72 (confidence interval [CI] 0.54-0.91) or 'moderate.' Discussion During our investigation, we noted that there was a technical learning curve related to poor contrast mixing and the need to titrate the concentration of Lumason. However, over the course of the study, we were able to correct the technical aspects. Ultimately, our results showed good correlation between VCUG and Lumason ceVUS and only slightly less correlation than published studies by experienced centers. Future studies with voiding should allow for improved urethral visualization. Conclusion While there is a considerable learning curve to the implementation of ceVUS for the diagnosis of pediatric VUR, these technical aspects can be corrected. Even a center previously naive to contrast-enhanced ultrasound technology can, over a short period of time, demonstrate good correlation between VCUG and ceVUS in the diagnosis of VUR. Translation of ceVUS into clinical practice is an alternative to VCUG for diagnosis of reflux, is feasible, and can eliminate the radiation exposure associated with a VCUG.