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 part 2: urethral imaging.

Ultrasound (US) has been increasingly used as an important imaging tool to assess the urethra in children. The earliest reports of pediatric urethral sonography involved imaging the urethra in a non-voiding state, during physiological voiding of urine, and after instillation of saline. The introduction of US contrast agents has continued to improve visualization of urethral anatomy. Contrast-enhanced US of the urethra can be performed during the voiding phase of a standard contrast-enhanced voiding urosonography (ceVUS) exam or with retrograde instillation of a contrast agent, depending on the exam indication. Both techniques are well tolerated by children and provide accurate information about urethral pathology and periurethral soft tissues. This article reviews the technical aspects and imaging findings of urethral pathologies in children using contrast-enhanced US, both by the voiding and retrograde instillation techniques.

Contrast-enhanced voiding urosonography, part 1: vesicoureteral reflux evaluation.

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.

Voiding urosonography and voiding cystourethrography in primary vesicoureteral reflux associated with mild prenatal hydronephrosis: a comparative study.

BACKGROUND: Contrast-enhanced harmonic voiding urosonography has been introduced as a sensitive, radiation-free imaging method for the diagnosis of vesicoureteric reflux. OBJECTIVE: To evaluate the occurrence/severity of vesicoureteric reflux in infants with mild prenatal hydronephrosis comparing voiding cystourethrography and voiding urosonography. MATERIALS AND METHODS: Sixty infants with prenatal hydronephrosis were studied (anteriοposterior pelvic diameter 5-9 mm on ultrasound [US] at gestational weeks 21-30). Postnatal US was performed within the first month of life, as well as voiding cystourethrography and contrast-enhanced voiding urosonography at 1.5-2.5 months at the same session. RESULTS: Vesicoureteric reflux was diagnosed on at least one modality in 19/60 (32%) infants, and more often on contrast-enhanced voiding urosonography (18/60, 30%) than on voiding cystourethrography (8/60, 13%), P=0.046. Among girls, reflux was more often seen on contrast-enhanced voiding urosonography (6/16, 38%) than on voiding cystourethrography (1/16, 6%), P=0.03. Vesicoureteric reflux missed by voiding cystourethrography was more severe (Grades I, II and III in one, nine and four kidney-ureter-units, respectively), compared with a single case missed by contrast-enhanced voiding urosonography (Grade I in one kidney-ureter-unit). CONCLUSION: In the absence of a reference standard, our results imply that voiding cystourethrography might underdiagnose reflux, and/or contrast-enhanced voiding urosonography may overdiagnose reflux.

Contrast-enhanced voiding urosonography: A new, radiation-free, alternative method for imaging of urinary bladder and urethra in healthy dogs.

Contrast-enhanced voiding urosonography (CE-VUS) has been generally considered as a promising tool to diagnose vesicoureteral reflux and abnormalities in lower urinary tract in human patients, especially in children. The purpose of this prospective study is to evaluate the quality of images of the urinary bladder and urethra obtained by CE-VUS using a second-generation ultrasound contrast agent (SonoVue®) in healthy dogs and to investigate the safety profile of SonoVue® after intravesical administration. Eighty-four CE-VUS examinations with SonoVue® were successfully performed in both unsedated (39/84) and sedated (45/84) dogs. Contrast-enhanced voiding urosonography examination of urinary bladder was technically successful in all (84/84) dogs. The image quality was not considered adequate in five (5/84) dogs including three dogs in whom layering of contrast media during filling phase was observed and two dogs with premature destruction of microbubbles. In these five dogs, the problem was readily recognized and corrected such that the procedure was still successfully undertaken. The assessment of the urethra during spontaneous micturition was successfully performed in all (84/84) dogs in whom voiding was elicited during the examination. No side effects were observed after intravesical application of SonoVue®. This study demonstrates that CE-VUS is a feasible and valuable technique to evaluate low urinary tract morphology and function in dogs. Based on our review of the literature, there are no published reports about the use of this method in dogs.

European Society of Paediatric Radiology Abdominal Imaging Task Force recommendations in paediatric uroradiology, part X: how to perform paediatric gastrointestinal ultrasonography, use gadolinium as a contrast agent in children, follow up paediatric testicular microlithiasis, and an update on paediatric contrast-enhanced ultrasound.

At the European Society of Paediatric Radiology (ESPR) annual meeting 2017 in Davos, Switzerland, the ESPR Abdominal (gastrointestinal and genitourinary) Imaging Task Force set out to complete the suggestions for paediatric abdominal imaging and its procedural recommendations. Some final topics were addressed including how to perform paediatric gastrointestinal ultrasonography. Based on the recent approval of ultrasound (US) contrast agents for paediatric use, important aspects of paediatric contrast-enhanced US were revisited. Additionally, the recent developments concerning the use and possible brain deposition of gadolinium as a magnetic resonance imaging contrast agent were presented. The recommendations for paediatric use were reissued after considering all available evidence. Recent insights on the incidence of neoplastic lesions in children with testicular microlithiasis were discussed and led to a slightly altered recommendation.

Standardization of pediatric uroradiological terms: a multidisciplinary European glossary.

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Paediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports and communication between different clinicians involved in pediatric urology and nephrology.

Standardization of pediatric uroradiological terms: A multidisciplinary European glossary.

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Pediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports and communication among different clinicians involved in pediatric urology and nephrology.

European Society of Paediatric Radiology abdominal imaging task force recommendations in paediatric uroradiology, part IX: Imaging in anorectal and cloacal malformation, imaging in childhood ovarian torsion, and efforts in standardising paediatric uroradiology terminology.

At the occasion of the European Society of Paediatric Radiology (ESPR) annual meeting 2015 in Graz, Austria, the newly termed ESPR abdominal (gastrointestinal and genitourinary) imaging task force set out to complete the suggestions for paediatric urogenital imaging and procedural recommendations. Some of the last missing topics were addressed and proposals on imaging of children with anorectal and cloacal malformations and suspected ovarian torsion were issued after intense discussions and a consensus finding process that considered all evidence. Additionally, the terminology was adapted to fit new developments introducing the term pelvicalyceal dilatation/distension (PCD) instead of the sometimes misunderstood hydronephrosis. The present state of paediatric urogenital radiology was discussed in a dedicated minisymposium, including an attempt to adapt terminology to create a standardised glossary.

Contrast-enhanced voiding urosonography with intravesical administration of a second-generation ultrasound contrast agent for diagnosis of vesicoureteral reflux: prospective evaluation of contrast safety in 1,010 children.

BACKGROUND AND OBJECTIVE: To evaluate the safety of intravesical administration of a second-generation ultrasound (US) contrast agent for the diagnosis of vesicoureteral reflux in children. MATERIALS AND METHODS: One thousand and ten children (563 girls, 447 boys; mean age: 2.9 years, range: 15 days-17.6 years) with 2,043 pelvi-ureter-units underwent contrast-enhanced voiding urosonography (ce-VUS) to rule out vesicoureteral reflux. A second-generation US contrast agent (SonoVue®, Bracco, Milan) was administered intravesically through transurethral bladder catheterization at a dose of 0.5 ml/bladder filling. Possible adverse events were monitored during the examination and followed up for 7 days after ce-VUS by phone calls. Urine analysis and culture were performed 3-5 days before ce-VUS in all children and 24-48 h in any patient who reported with adverse events. RESULTS: No case of serious adverse event was recorded. Minor events were reported in 37 children (3.66% of the study population). These included dysuria (n = 26, 2.57%), urinary retention (n = 2, 0.2%), abdominal pain (n = 2, 0.2%), anxiety (n = 1, 0.1%) and crying (n = 1, 0.1%) during micturition, blood and mucous discharge (n = 1, 0.1%), increased frequency of micturition (n = 1, 0.1%), vomiting (n = 1, 0.1%), perineal irritation (n = 1, 0.1%), and an episode of urinary tract infection 10 days after ce-VUS (n = 1, 0.1%). Of these adverse events, 91.9% were subacute in onset and 8.1% were delayed. All events were self-limited and none required hospitalization. CONCLUSION: There were no serious adverse events. Only a few minor events were reported, most likely due to the catheterization process. Thus, ce-VUS with intravesical administration of the second-generation US contrast agent (SonoVue®) for vesicoureteral reflux detection or exclusion had a favorable safety profile in our study group.

Growth and function in childhood of a normal solitary kidney from birth or from early infancy.

BACKGROUND: Children with a solitary kidney (SK) have an increased long-term risk of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed the early signs of impaired glomerular filtration in children with a SK from birth or from early infancy. METHODS: Renal growth and function at ages 4-15.5 years were studied in 38 children with SK and 40 matched control subjects in terms of accelerated growth. RESULTS: The systolic/diastolic blood pressure Z-scores (p = 0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p = 0.05) were higher in the children with SK. Creatinine clearance and 24-h protein and albumin urinary excretion showed no difference. All but seven children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate values of >80 ml/min/1.73 m(2). An independent positive correlation was found between length of the follow-up time and 24-h albumin urinary excretion (ß = 0.54, p < 0.01). Accelerated postnatal growth was positively related with kidney volume (ß = 0.35, p < 0.05). CONCLUSIONS: Among our patient cohort, renal function was well preserved at ages 4-15.5 years in children who were born with a SK. However, both their higher blood pressure and RI and the correlation of 24-h albumin urinary excretion with length of follow-up time underline the need for monitoring to detect early signs of glomerular hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy was found to be correlated with postnatal growth.

Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the Society for Pediatric Radiology (SPR) and the International Contrast Ultrasound Society (ICUS).

The practice of contrast-enhanced ultrasound in children is in the setting of off-label use or research. The widespread practice of pediatric contrast-enhanced US is primarily in Europe. There is ongoing effort by the Society for Pediatric Radiology (SPR) and International Contrast Ultrasound Society (ICUS) to push for pediatric contrast-enhanced US in the United States. With this in mind, the main objective of this review is to describe the status of US contrast agent safety in non-cardiac applications in children. The five published studies using pediatric intravenous contrast-enhanced US comprise 110 children. There is no mention of adverse events in these studies. From a European survey 948 children can be added. In that survey six minor adverse events were reported in five children. The intravesical administration of US contrast agents for diagnosis of vesicoureteric reflux entails the use of a bladder catheter. Fifteen studies encompassing 2,951 children have evaluated the safety of intravesical US contrast agents in children. A European survey adds 4,131 children to this group. No adverse events could be attributed to the contrast agent. They were most likely related to the bladder catheterization. The existing data on US contrast agent safety in children are encouraging in promoting the widespread use of contrast-enhanced US.

Evaluation with contrast-enhanced magnetic resonance imaging of the anterior cruciate ligament graft during its healing process: a two-year prospective study.

OBJECTIVE: The aim of this study was to evaluate, with contrast-enhanced-magnetic resonance imaging (MRI), the changing imaging appearance of an anterior cruciate ligament (ACL) graft during the revascularization phase by quantitatively assessing the morphological and signal intensity changes taking place at its cross-sectional surface over time. MATERIALS AND METHODS: Fifty patients underwent contrast-enhanced-MRI on the third postoperative day and at a mean of 6, 12, and 24 months time interval after surgery. Proton-density images were obtained to evaluate morphological and signal intensity characteristics. Oblique-axial T1-weighted images obtained before and after intravenous gadolinium administration were used for quantitative analysis. Enhancement index (EI: signal-to-noise quotient(after gadolinium)÷signal-to-noise quotient(before gadolinium)) and cross-sectional area (CSA) were calculated for two regions of interest: the transplanted graft and its surrounding hypervascular tissue, and at three distinct graft sites (intra-articular, intraosseous tibial tunnel, and intraosseous juxta screw sites). Comparisons of EI and CSA at every site and time interval were performed using analysis of variance. RESULTS: A variable MRI appearance of the graft during the different time intervals was attributed to the varying amount of the hypervascular tissue gradually surrounding the graft. Graft EI and peripheral tissue CSA progress in a parallel, time- and site-related pattern along the graft course. The initial heterogeneity with intermediate signal intensity at the intra-articular graft site reflected intense revascularization. A slower revascularization progress was noticed at the other two intraosseously enclosed sites. CONCLUSION: During the healing process the amount of revascularization tissue influences the MR imaging characteristics of the graft according to the examined site and the time interval after surgery. By 2 years postoperatively, revascularization completion coincides with the homogeneously low signal intensity of the graft, closely resembling native ACL.

ESPR Uroradiology Task Force and ESUR Paediatric Working Group--Imaging recommendations in paediatric uroradiology, part V: childhood cystic kidney disease, childhood renal transplantation and contrast-enhanced ultrasonography in children.

The ESPR Uroradiology Task Force and the ESUR Paediatric Working Group present two new recommendations on imaging in childhood cystic kidney disease and in childhood renal transplantation, and address the presently restricted availability of contrast-enhanced (ce) US in children. New insights into the genetics require an updated classification of paediatric cystic kidney disease along with a new concept of diagnostic imaging. Characteristic imaging features are key to the new classification. Available recommendations for imaging renal transplantation in children are not satisfactory. The following consensus-based algorithm proposes a more effective and more uniform imaging concept, reducing invasiveness, enhancing diagnostic accuracy, and facilitating future multicentre studies and meta-analysis. At present, ce-US in children can only be performed off-license, since the only approved US contrast agent (CA) for children has been taken off the market. Nevertheless, paediatric ce-US is practiced at multiple places using Sonovue (Bracco, Milan, Italy), a generally available agent in Europe. From a medical and scientific perspective, paediatric ce-US should be promoted, and efforts are undertaken to collect data on paediatric US-CA applications. Routine paediatric imaging depends on local expertise and availability of equipment. The imaging recommendations and supportive data are intended to ease the physicians' difficult task of dealing with the specific diagnostic demands of paediatric paediatric cystic kidney disease and transplantation.

Renal function and kidney length in preterm infants with nephrocalcinosis: a longitudinal study.

Renal injury in early life may lead to hypertension and renal disease in adulthood. In this prospective study, we estimated renal glomerular and tubular function and kidney length (KL) during the first 2 years of life of preterm infants with nephrocalcinosis (NC) associated with prematurity. The study cohort comprised 107 preterm children, 63 with NC and 44 control subjects without NC who were matched for gender, gestational age and birth weight. Kidney function was estimated based on measurements of serum creatinine (Scr), estimated glomerular filtration rate (eGFR), fractional excretion (FE) of sodium (Na), potassium (K), phosphate (P), magnesium (Mg) and uric acid (UA) and on the ratios of urinary Ca, oxalate (UOx) and citrate (UCit) to urinary creatinine (UCa/Ucr, UOx/Ucr and UCit/Ucr, respectively) calculated from morning urine collections. KL was measured by ultrasonography. Measurements were made at 40 weeks postmenstrual age and at 3, 6, 12 and 24 months of age. At 3 and 6 months, the NC group had higher UCa/Ucr, FEK and FEUA than the control group; at 12 months, only the UCa/Ucr and FEUA was still higher. The UCa/UCit ratio was higher in the NC group. Scr and eGFR did not differ between the groups at any time point. The NC group had a shorter KL up to 12 months of life (left kidney) or 24 months (right kidney). Based on these results, we conclude that NC in the preterm infants enrolled in our study was associated with impaired renal tubular function and a shorter KL in the first year of life.

Revascularization process of the bone--patellar tendon--bone autograft evaluated by contrast-enhanced magnetic resonance imaging 6 and 12 months after anterior cruciate ligament reconstruction.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (MRI) studies conducted on animal models have shown that the observed signal intensity changes are related to the degree of graft vascularity and its biomechanical properties. PURPOSE: To evaluate by contrast-enhanced MRI the revascularization process at 3 distinct sites discerned in relation to the surrounding microenvironment along the course of bone-patellar tendon-bone (BPTB) autograft in uncomplicated human anterior cruciate ligament (ACL)-reconstructed knees. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two male patients were assessed with a 3-dimensional fast field echo/short tau inversion recovery (FFE/STIR) MRI sequence at the third postoperative day and at time intervals of 6 and 12 months after surgery. Signal-to-noise quotient (SNQ) was calculated for 3 specific graft sites (intra-articular site, intraosseous tibial tunnel site, and intraosseous juxta screw site) before and after gadolinium administration. Comparisons of the enhancement index (EI: SNQ(after)/SNQ(before) gadolinium) were performed independently for each graft site and time interval. RESULTS: Three days postoperatively, insufficient vascularization was noticed at the 3 sites. Six and 12 months after surgery, the enhancement index was significantly increased in all 3 sites (P < .001). The intra-articular site, 6 months postoperatively, achieved satisfactory contrast medium uptake (enhancement index >1), with significantly higher enhancement index values compared with the other 2 sites (P < .001). Twelve months after surgery, only the intraosseously enclosed sites displayed an increase of the enhancement index, although nonsignificant (P = .09 and P = .07, respectively). CONCLUSION: Revascularization of the graft occurs gradually along its length, with the intra-articular site being the first and the faster part to complete this phase, while both the intraosseous sites are still in progress throughout the first postoperative year. Revascularization is an important link at the intrinsic healing chain of the ACL graft. The surrounding microenvironment does seem to play a significant role in this process, and the differences in its composition along the graft course are reflected at the revascularization progress of the corresponding sites.

Kidney growth in twin children born small for gestational age.

BACKGROUND: Low birth weight (LBW) is associated with adult-onset diseases, including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie related prenatal programming. No data are available on longitudinal renal growth in twin infants born small for gestational age (SGA). The aim of this prospective longitudinal study was to estimate the renal size during the first 2 years of life in SGA twin infants. METHODS: The study included 613 children, of which 145 were SGA twins, 141 twins appropriate for gestational age (AGA), 148 matched AGA singletons and 179 matched SGA singletons, classified according to GA into two groups (28-36 and >36 weeks). The SGA children were also classified according to the degree of IUGR: birth weight (BW) <3rd percentile and BW 3rd-10th percentiles. Serial renal ultrasonography (US) for kidney length (KL) measurement was performed at the ages of 36 and 40 weeks corrected age (CA) and 3, 6, 12 and 24 months of age, and KL was related to other anthropometric indices. Twin data were examined both as individuals and as members of twin pairs. RESULTS: A total of 2317 measurements were performed. KL was lower at 40 weeks CA in all the SGA twin subgroups. In the SGA twins with GA >36 weeks, KL increased thereafter and became similar to AGA twins and single AGA control subjects. Among pre-term infants of GA <36 weeks, only those with BW 3rd-10th percentile experienced catch-up in KL, while in those with BW <3rd percentile, KL remained lower than in AGA infants throughout the study period, both in absolute terms and relative to other anthropometric indices. No differences in KL were found between twin SGA and singleton SGA or between twin AGA and singleton AGA infants. Intrapair BW differences were correlated with the intrapair differences in KL. CONCLUSIONS: Twin SGA infants born prematurely with BW <3rd percentile are unable to achieve catch-up in KL in the first 24 months of life, and long-term follow-up is recommended.

Implications of 99mTc-DMSA scintigraphy performed during urinary tract infection in neonates.

OBJECTIVE: To evaluate prospectively whether normal scintigraphic results during urinary tract infections (UTIs) in neonates were predictive of the absence of dilating vesicoureteral reflux (VUR) (grade > or =III) and permanent renal damage (PRD). METHODS: Term neonates with a first symptomatic, community-acquired UTI participated in the study. Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months. DMSA scintigraphy, to determine the development of PRD, was repeated 6 months after UTI. RESULTS: Seventy-two neonates (144 renal units) were enrolled. Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19% of renal units, VUR in 22%, and grade > or =III VUR in 13%. The majority (71%) of renal units with grade > or =III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade > or =III VUR were 29% (95% confidence interval: 11%-55%) and 82% (95% confidence interval: 74%-88%), respectively. PRD was found in 7% of renal units, all of which had abnormal early DMSA scintigraphic results. PRD was significantly more frequent among renal units with grade > or =III VUR than among nonrefluxing renal units (P < .05). CONCLUSIONS: Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR. To rule out dilating VUR, voiding cystourethrography may be required.

The effects of gestational age and growth restriction on compensatory kidney growth.

BACKGROUND: Low birth weight is associated with altered renal development, adult onset hypertension and renal disease. The aim of this prospective longitudinal study was to estimate the renal growth during the first 2 years of life in small-for-gestational age (SGA) infants of varied gestational age (GA) and with differing degrees of growth retardation (GR) at birth. Material and methods. The study included 466 children: SGA, n = 243, and appropriate-for-gestational age (AGA), n = 223, classified according to GA into three groups (28-34, 34-36 and >36 weeks, respectively). The SGA children were also classified according to the degree of GR: birth weight <3rd percentile, and birth weight 3-10th percentiles. Serial renal ultrasonography (US) for kidney length (KL) measurement was performed at the ages of 36 and 40 weeks corrected age and 3, 6, 12 and 24 months of chronological age. The ratios of KL(3) to crown to heel length (CHL), body weight (BW) and body surface area (BSA) were used as estimators of relative kidney length (RKL). RESULTS: A total of 1898 measurements were performed. In the full-term and near-term SGA infants (GA >36 weeks), RKL was similar to or even higher than that in AGA controls (P < 0.05 at 12 and 24 months). In two groups of preterm infants (GA 34-36, 28-34 weeks), RKL was lower than in AGA controls either after the first 6 months (GA 34-36 group, P < 0.05) or throughout the study period (GA 28-34 group, P < 0.05). The absolute KL was more severely affected in the preterm babies (GA <36 weeks) with BW <3rd percentile than in those of GA 3rd-10th percentile. CONCLUSION: While in full-term and near-term SGA infants RKL is similar to or even higher than that of AGA infants, in smaller preterm babies (<36 weeks of GA) the RKL is impaired up to the second year of life.

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

BACKGROUND: 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. OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.