An innovative diagnostic procedure in children: videourodynamics with contrast-enhanced voiding urosonography

Abstract

Contemporary videourodynamic (VUD) investigation combines voiding cystourethrography (VCUG) and urodynamics into one study, which allows simultaneous visualization of the urinary tract by ionizing radiation alongside the measurement of sensation, capacity, compliance, and detrusor pressure during bladder filling and voiding using one double lumen catheter. Today VUD is a benchmark for evaluating the lower urinary tract disorders in children because it evaluates urinary bladder and sphincter function and visualizes bladder morphology and vesicoureteral reflux (VUR) presence at the same time. Several previous studies of fluoroscopic videourodynamics issued concerns regarding radiation exposure. This technical report aims to describe a new modality of VUD in children by replacing fluoroscopic VCUG with contrast-enhanced voiding urosonography (ceVUS). ceVUS using second-generation contrast media and harmonic imaging is a radiation-free and highly sensitive imaging modality used to detect VUR in children. We simultaneously performed an infusion of ultrasound contrast through the double lumen urodynamic catheter during urodynamic evaluation. This article describes the advantages of this method compared with a conventional technique. In addition to being radiation-free, this procedure of advanced videourodynamics method can better detect vesicoureteral reflux and intrarenal reflux combined with urodynamic disorders associated with VUR.

Introduction

Lower urinary tract dysfunction (LUTD) in children is a common urological issue, often associated with urinary tract infection (UTI) and vesicoureteral reflux (VUR). As the association between non-neurogenic and neurogenic LUTD and VUR is common and often accompanied by bowel dysfunction, it is recommended to consider bladder and bowel function in patients with VUR and vice versa. LUTD in children with VUR increases the risk of renal scarring, reduces the success rate of antireflux endoscopic surgery, and increases the risk of postoperative UTI irrespective of VUR surgical success rate [1]. Alternatively, it is possible that LUTD is secondary to a high-grade VUR and that treatment of VUR will therefore result in correction of LUTD. VUR associated with LUTD resolves with targeted treatment in 45% of ureters, with no difference in resolution rates among grades I to V [2].

Conventional videourodynamics (VUD) combines fluoroscopic voiding cystourethrography (VCUG) with a multichannel urodynamic investigation into a single study using one double lumen catheter. This imaging modality allows simultaneous visualization of the urinary tract, shows the presence of VUR, and simultaneously measures functional parameters like sensation, capacity, compliance, rectal, intravesical, and detrusor pressures during bladder filling voiding on the urodynamic screen. Urodynamic measurements are recorded on a computer and VUR roentgenogram images. Simultaneous investigation of the anatomy and function of the lower urinary tract allows proper diagnosing of lower urinary tract dysfunction, bladder volume influence, and pressures at the occurrence of VUR, guiding therapeutic decisions [3]. Nevertheless, several previous studies show that videourodynamics entails significant radiation exposure [4–6].

Contemporary radiation awareness and protection guidelines in infants and children suggest using minimal doses of radiation as reasonably achievable or completely avoided if possible [4, 5, 7]. Growing tissues of children during development are more sensitive to radiation exposure, and children have a longer life expectancy during which radiation's potential oncogenic effects may eventually manifest [9–11]. The growing number and diversity of genitourinary tract tumors can indeed be addressed to different oncogenic impacts with cumulative effects [8, 9]. Repeated VCUG procedures may significantly increase the risk of such tumors. The value of Contrast-Enhanced Ultrasound (CEUS) in differentiating genitourinary masses instead use of radiation exposure procedures is already recognized [10].

Materials and methods

The selection criteria for VUD include a history of repeated UTI in toilet-trained children, a small bladder capacity not responding to urotherapy and anticholinergics, dysfunctional uroflow not responding to biofeedback, incontinent children resistant to treatment, VUR diagnosed in a child after a toilet training, or follow up of a child with a previously diagnosed neurogenic or non-neurogenic bladder and bowel dysfunction and VUR.

Primary non-invasive assessment tools include questionnaires of a child’s previous illnesses and family history, physical examination, urine analysis, standard kidney ultrasound (US), and uroflow. Further assessment is invasive and consists of a urodynamic study and VCUG, a radiation-inclusive method. We have combined a urodynamic study and contrast-enhanced voiding urosonography (ceVUS), an up-to-date, highly sensitive imaging method for detecting VUR in children, to form a radiation-free VUD study. Both procedures are performed simultaneously, which is preferable as less invasive if completed in one study [1]. Here we describe this method in detail.

1. Detailed US examination of the urinary tract before catheter insertion

2. First, the standard US of the urinary tract in the supine and prone position was performed on a machine equipped with application-dedicated software for contrast-enhanced studies with a harmonic imaging modality and low or intermediate mechanical index (MI, 0.04–0.10).

3. Second, a detailed US scan of the urinary tract was first carried out in greyscale with the tissue-specific harmonic imaging modality in both the transverse and longitudinal planes. A high-frequency linear transducer (7.5–10 MHz) is used for infants and small children, and a low-frequency convex transducer (3.5–5 MHz) for older children. Particular attention is given to documenting subtle changes in the retrovesical region, the vesicoureteral junction, and dilated ureter. The renal pelves are imaged with maximum magnification.

4. Third, the kidneys' size, position, and shape are documented. Parenchymal scarring, pelvicalyceal and ureteral duplication, dilatation of the ureteral collecting system, bladder wall thickness, and dilatation of the distal ureters are particularly estimated.

5. Uroflow is performed in toilet-trained children

6. US study of the urinary tract after voiding. Kidneys and bladder are scanned repeatedly to determine potential postvoid dilatation of ureters and the collecting system, and the possible bladder residual urine.

7. Bladder catheterization was performed with a double-lumen 6F or 8F catheter to measure bladder filling alongside intravesical pressure. Urethral and rectal catheters are used to obtain the intravesical (Pves) and intraabdominal pressure (Pabd) recordings. Detrusor pressure is automatically calculated by subtracting intraabdominal from intravesical pressure to correct changes that might occur during laughing, talking, coughing, or US probe pressure. A single lumen 8F catheter or a rectal balloon catheter is used for rectal pressure measurement (Pabd).

All pressures are measured using a transducer and recorded on the computer. Calibrating the equipment according to the specifications of the manufacturer is conditio sine qua non. All methods, definitions, and units are estimated to the standards recommended by the ICCS [11].

Physiological normal saline at 37 °C and a freshly prepared suspension of the US contrast medium (SonoVueR, Bracco) are prepared strictly following the manufacturer's instructions. SonoVue contrast is added to a 250–500 mL bag of saline in concentration 0.5–1%. The bladder is progressively and homogeneously filled at 10% of the expected bladder capacity per minute. Bladder capacity (in milliliters) is calculated using the following formula: volume = (age + 1) × 30, where age is in years or (weight in kilograms × 7) ml for children less than 12 months of age.

Suppose the child has a neurogenic bladder and no sensation. In that case, the filling should be continued until the child feels uncomfortable, has detrusor pressure greater than 40 cm H₂O, and/or infused volume is more than 150% of expected capacity, or the leakage rate is greater than the infusion rate. Simultaneously with US monitoring, urodynamic equipment measures detrusor activity, bladder sensation, bladder capacity, and bladder compliance.

• 5.Continuous, alternate examination of right and left kidneys and urinary bladder is performed after administration of US contrast medium during bladder filling and voiding. The diagnosis of VUR is made when the echogenic microbubbles appear in the ureter or the renal pelvis. The microbubbles render the echo-free lumen echogenic when the ureter is distinctly visible behind the bladder. The diagnosis of VUR is determined by the presence of moving echogenic microbubbles from US contrast in the upper urinary tract. The five-grade system developed by Darge and Troeger is used [12]. The US examination is continued during and after voiding, similarly as above. Children capable of voiding are placed in the sitting position, and younger children stay in a supine position during micturition. Voiding pressures are continually measured during the whole procedure. If a child is sitting during voiding, kidneys are scanned from the back. The urinary tract during and after voiding is surveyed alternately.
• 6.Optionally, a transperineal US of the urethra during cyclical filling of the bladder may be added, and the configuration of the urethra during voiding is monitored.
• 7.During VUD-ceVUS, we use harmonic imaging, which increases the contrast and spatial resolution and can partially reduce a certain number of artifacts observed by previous imaging methods. The resulting images are more transparent and sharper. Also, with harmonic imaging, there is an increase in the VUR detection rate of 30% [13, 14]. Contrast-specific harmonic imaging mode, together with the subtraction technique, further increases the conspicuity of the microbubble. Setting a mechanical index (MI) below 0.10 is essential to break the microbubbles of the second-generation US contrast medium. Improvements in US techniques have reduced the disadvantages of the previous method of ceVUS detection [13].

Systemic complications of ceVUS are infrequent. There were no systemic complications or allergic reactions related to intravesical use of SonoVue. A few non-serious adverse events were encountered (0.31%; 38/12.362), most likely attributable to the bladder catheterization rather than the US contrast medium [15].

The study is performed by the trained, experienced nurse practitioner alongside qualified pediatric nephrologist or pediatric radiologist. No sedation is required. Parents/guardians and older children are informed in detail prior to the entire procedure. They are also provided with a written leaflet describing the whole process. Antibiotic prophylaxis is used.

All steps are shown in Fig. 1.

Fig. 1.

Urodynamic page with simultaneous ceVUS monitoring. Arrows show intravesical pressure and volume that correspond to the ce-VUS image

Discussion

As VUR, especially if combined with intrarenal reflux (IRR), is a fleeting phenomenon due to the brevity of image sequencing, it can be missed during the fluoroscopic study due to the performer’s avoidance of ionizing radiation. As fluoroscopic VCUG depends on timely performed imaging, VUR might be missed even if high-graded because of the various techniques used in VCUG, possible inadequate bladder filling, the dilution of a minute amount of radiographic contrast in the already-dilated collecting system, obscuration by overlying bowel shadow, and too narrow collimation of the X-ray field, focusing only on the bladder and urethra during micturition [16].

ceVUS is a method recommended in the joint guidelines for the urological examination issued by the European Society of Urogenital Radiology (ESUR) and the European Society of Paediatric Radiology (ESPR) since 2007 [17, 18]. Since 2012 it is also in the guidelines for imaging of the urethra and UTIs in boys [19]. The main drawback of ceVUS is the acoustic shadowing produced by the high concentration of US contrast particles that decreases the sensitivity in detecting a grade I reflux. This can be counteracted by the dilution of the US contrast with the continuous saline infusion [13].

The dilution of radiographic contrast in the dilated collecting system and superposition by the overlying bowel contributes to the limited VCUG sensitivity [14]. ceVUS is reported to be more sensitive than VCUG because of continuous scanning and the potential to detect intermittent VUR and IRR [14]. Compared to VCUG, ceVUS has superior sensitivity ranging from 80 to 100% and a specificity of 77–97% [20, 21]. Data show that VCUG misses 6–62% of all reflux units [20]. ceVUS examination technique misses only 0–12% of all reflux units [22].

VUD-VCUG examination is widely used in pediatric and adult nephrology/urology in estimating lower and upper urinary tract dysfunction. It provides helpful information for managing VUR by identifying neurogenic LUTD and upper urinary tract conditions in a single comprehensive test, especially in myelomeningocele, even in neonatology [23, 24]. Postoperative VUD-VCUG serves to evaluate the VUR disappearance after surgery [25]. If VUD-VCUG needs to be repeated, the ionizing effect accumulates over time.

Our experiences with VUD-ceVUS, although with a limited number of cases, point to three advantages. First, the detection of VUR remained at around 38% due to the extended observation time during ceVUS [13, 14]. Secondary, the detection of IRR remained at similar percentages as in fluoroscopic VCUG (11.9%), although there are authors who indicate a higher rate of IRR [26]. IRR's importance is reflected as a risk factor for reflux nephropathy because it directly allows urine (and bacteria) to enter the renal tubular system. We believe that IRR will play an essential role in assessing the need for UTI prophylaxis in the future. Third, during the examination, the contrast can be correctly dosed and repeated, thus avoiding one of the most critical fluoroscopic VCUG sensitivity limitations, namely dilution of radiographic contrast in the dilated collecting system and superposition by the overlying bowel.

VUD-ceVUS can be repeated as needed and ordered again in unclear diagnoses. This is particularly important in assessing postoperative procedures for meningomyelocele in newborns [25]. Further research and evaluations are in progress.

Conclusions

Simultaneously with a urodynamic study, a ceVUS using second-generation urinary contrast can be introduced as a valid noninvasive diagnostic modality for detecting VUR and LUTD based on its radiation-free, highly efficacious, reliable, repeatable, and safe characteristics. Due to better detection of VUR and possibly IRR, VUD-ceVUS can better detect urodynamic disorders in children, which is particularly important for LUTD anomalies in newborns. VUD-ceVUS can guide accurate drug treatment strategy and direct surgical intervention in children with VUR.

Abbreviations

ceVUS

Contrast-enhanced voiding urosonography

IRR

Intrarenal reflux

LUT

Lower urinary tract

LUTD

Lower urinary tract dysfunction

US

Ultrasound

VCUG

Voiding cystourethrography

VUD

Videourodynamics

VUD-VCUG

Voiding cystourethrography with urodynamics

VUD-ceVUS

Videourodynamics combined with contrast-enhanced voiding urosography

VUR

Vesicoureteral reflux

VUS

Voiding urosonography

UTI

Urinary tract infection

Funding

The authors have not disclosed any funding.

Declarations

Conflict of interest

The authors have not disclosed any competing interests.