| Abstract|| |
Objective : We prospectively compared echocontrast cystosonography (ECS) using 'agitated saline' with micturating cystourethrography (MCU) for the detection of vesicoureteral reflux (VUR). Subjects and methods : Fifty-one children (39 boys and 12 girls) ranging from nine days to twelve years underwent ECS followed by MCU for the evaluation of VUR. Both procedures were performed on the same day and by the same radiologist throughout the study. After confirming the absence of urinary infection, children were catheterized under strict aseptic conditions. Baseline renal and bladder sonograms were obtained. The bladder was filled to capacity by slow injection of normal saline. Five to ten ml of air was then injected to generate microbubbles 'in vivo'. The sonographic criteria used for the diagnosis of reflux were (1) increase in dilatation and (II) visualization of moving microbubbles within the collecting system. No attempt at grading the reflux was made. The findings were compared with the 'gold standard' micturating cystourethrogram. Results : Of the hundred kidney-ureter units studied, twenty-two showed reflux at MCU. ECS could detect reflux in twenty (100 percent of grade I, 67 percent of grade II, 86 percent of grade III, 100 percent of grade IV and V reflux) of these units. 'Visualization of moving microbubbles' as a sonographic criterion of reflux was 91 percent sensitive, 100 percent specific and 98 percent accurate, whereas 'increase in dilatation' was less sensitive (77 percent), specific (83 percent) and accurate (82 percent). Conclusion : ECS using 'agitated saline' is a sensitive, accurate and safe imaging technique for the detection of VUR. The 'visualization of moving microbubbles' within the collecting system is a definitive sonographic sign of reflux. The observation of 'increase in dilatation' alone should be viewed with suspicion. MCU continues to be the primary diagnostic tool in view of its ability to grade reflux and reveal bladder and urethral anatomy. Cystosonography obviatesexposure to radiation and is therefore recommended for follow-up examinations and screening of asymptomatic siblings.
Keywords: Echocontrast Cystosonography, Vesicoureteral Reflux, Agitated Saline
|How to cite this article:|
Katariya S, Chaudhry S, Pimpalwar A, Rao K. Saline Cystosonography versus micturating cystourethrography in the detection of vesicoureteral reflux. Indian J Radiol Imaging 2003;13:45-52
Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the renal collecting system. It provides a pathway for ascent of bacteria and along with infection results in renal scarring. The risk of subsequent hypertension and renal insufficiency can be reduced by early diagnosis and treatment. Roentgenographic micturating cystourethrography (MCU) and radionuclide cystography are the traditional diagnostic procedures used for this purpose. Both these imaging tools expose the young patient to ionizing radiation. The average effective dose for an MCU involving three radiographs and fluoroscopy is 0.3 to 0.4 mSv . The stomach, lower large intestine, bladder wall, liver and ovaries receive relatively high doses  The gonad dose during an MCU ranges from 53 to 1900 m rad in girls and from 24 to 309m rad in boys . 99mTc direct radionuclide cystography delivers an 'absorbed dose' of 16mrad/mCi to 58mrad/mCi to the bladder wall and a radiation dose rate of 0.2mrad/mCi-min to the testes and 0.3mrad/mCi-min to the ovaries in a five-year-old . Also, conservative management of children with reflux entails frequent follow-up imaging; increasing the concern over radiation exposure.
|How to cite this URL:|
Katariya S, Chaudhry S, Pimpalwar A, Rao K. Saline Cystosonography versus micturating cystourethrography in the detection of vesicoureteral reflux. Indian J Radiol Imaging [serial online] 2003 [cited 2020 Jun 6];13:45-52. Available from: http://www.ijri.org/text.asp?2003/13/1/45/28627
Ultrasound is an attractive imaging modality for the pediatric population. It involves no ionizing radiation and is well tolerated by the young. Ultrasound by itself, however, is neither sensitive nor specific for the diagnosis of VUR ,. Children with abnormal screening renal sonograms often have VUR, but a normal sonogram does not reliably exclude the condition . Increase in renal pelvic size on post-void ultrasound is also not a reliable indicator of VUR .
The introduction of contrast agents into the bladder increases the echogenicity of bladder fluid and allows real-time sonographic visualization of retrograde movement of the echogenic fluid into the ureter and the pelvicalyceal system (PCS). This prospective study evaluates the efficacy of cystosonography using agitated saline in the detection of VUR.
| Subjects and methods|| |
Patient population and study setting
The study was conducted in the radiology department of a tertiary care children hospital from April 1998 to March 1999. Fifty-one patients (39 boys and 12 girls) ranging in age from nine days to twelve years were referred from the pediatric out patient department for the detection or follow-up of VUR.
The clinical indications for the study included obstructive urinary symptoms (n=12), repeated urinary tract infection (n=14), dysfunctional voiding (n=3), incidentally detect ed hydroureteronephrosis (n-5), anorectal malformat ion (n=5), exstrophy epispadias complex (n=2) and follow-up examinations in the course of conservative / surgical management (n=10). Two patients had a solitary kidney, hence a total of hundred kdney - ureter (K-U) units were evaluated for reflux. The study was approved by the Ethics Committee of the hospital.
All patients underwent echocontrast cystosonography (ECS) followed by MCU on the same day. They were free from urinary tract infection for at least one week prior to the procedure [7,8]. An informed consent was obtained from the parents before the procedure. All children less than five years of age received oral sedation in the form of trichlorphos (30-50mg/kg) thirty minutes before the procedure. Urethral catheterization was performed with an appropriate sized Foley's catheter or infant feeding tube under strict aseptic conditions. The residual urine was discarded and the catheter connected to a three-way through a short connecting tube.
Baseline renal and bladder sonography was performed using a real time ultrasound scanner (Sonoline SI-450) equipped with a 7.5 MHz linear and 3.5 MHz curvilinear transducers. A transverse image of the bladder and sagittal images of both kidneys were obtained and documented on a film. Normal saline at room temperature was then slowly instilled into the bladder with a 20 ml syringe connected to the three-way till the bladder was filled to capacity. This was followed by injection of 5-10 ml of air with moderate force over 5-7 seconds to generate microbubbles. Renal and bladder sonography was performed during injection and the post injection images were documented. Because the microbubbles underwent gradual dissolution, a second injection of 10ml of air was done to evaluate the opposite side.
The sonographic criteria used for the detection of reflux were (I) increase in dilatation of the ureter and / or the PCS and (II) real-time visualization of moving microbubbles within the ureter and / or the PCS during air injection. There was no attempt at grading the reflux on ECS.
The bladder was emptied via the catheter and an MCU was performed on the same day to avoid repeated catheterization. Reflux was graded according to the International Reflux Study Committee classification . All sonographic and radiographic examinations were performed and interpreted by the same radiologist throughout the study.
The two sonographic criteria were compared separately with the 'gold standard' micturating cystourethrogram and their sensitivity, specificity, accuracy, positive predictive value and negative predictive values were calculated.
Of the hundred K-U units studied, twenty-two showed reflux on MCU. The distribution of the reflux on MCU was (i) no reflux in seventy eight units (ii) grade I in one unit, (iii) grade II in three units, (iv) grade II seven units, (v) grade IV in two units, and (vi) grade V in nine units. ECS could detect reflux in twenty (100% of grade I, 67% of grade II, 86% of grade III, 100% of grade IV and V reflux) of these units [Figure - 1][Figure - 3]. The findings at ECS are compared with the findings at MCU in [Table - 1]. This data shows the false positives and negatives for the two criteria.
Thirteen K-U units showed increase in dilatation on ECS [Figure - 2] but no reflux on MCU. These cases were considered to represent false positive for criterion I. There were no false positives for criterion II.
Two K-U units refluxing at MCU showed no increase in dilatation or moving microbubbles on ECS. These were considered false negatives for both sonographic criteria. Three K-U units refluxing at MCU showed moving microbubbles without increase in dilatation on ECS [Figure - 4][Figure - 5]. These cases were considered to represent false negatives for criterion I.
Graph 1 shows a comparison between the two sonographic criteria and [Table - 2] shows a comparison with other studies.
Diagnosis and characterization of vesicoureteral reflux for ages has been done with fluoroscopic and radionuclide voiding cystography. These procedures entail ionizing radiation and justify the use of safer imaging modalities. Cystosonography with echogenic contrast medium seems to be an attractive proposition and has been evaluated in a number of experimental and clinical studies in the recent years . A variety of contrast agents have been used for this purpose [cysto-conray, agitated saline, CO2 bubbles, sonicated albumin and microcrystaline galactose suspensions].
'Agitated saline' was used to provide sonographic contrast in our study. We tried to overcome the difficulty of bubble instability experienced by Hanbury et al  by modifying the technique of agitation. The saline was agitated 'in vivo' unlike 'in vitro' agitation used by these workers. This procedure generated adequated microbubbles to make the bladder fluid echogenic and to observe its retrograde movement into the refluxing K-U unit.
The sonographic criterion of real-time 'visualization of moving microbubbles' had an excellent correlation with MCU [Figure - 1]. There were no false positive and two false negatives with this criterion. 'Increase in dilatation' during injection was found to be less sensitive, specific and accurate for t he detection of reflux. There were thirteen false positives and five false negatives with this criterion. This was in contrast with the findings of Schneider et al , who found the 'separation of the central renal echo complex' to be more sensitive (87.2%) than the 'visualization of bubbles' in the ureter (73%).
False Positive on ECS
Of the thirteen false positive results for criterion 1 [Figure - 2], two patients had previously undergone radionuclide cystography and were found to reflux. Radionuclide studies in the past have revealed reflux in patients with a negative MCU . It is also well established that reflux is an intermittent phenomenon and hence the continuous monitoring during voiding in a radionuclide study is more likely to detect reflux than the brief glimpses at fluoroscopy. Because sonography permits a prolonged period of observation throughout bladder filling ,, it is quite possible that our 'false positives' may actually be 'true-positives'. Similar high false positivity at sonography has been reported by other workers ,. The use of MCU as the 'gold standard' has therefore been questioned . Because of absence of radionuclide studies in the entire study group, it is difficult to come to a definite conclusion.
False Negatives on ECS
There were two false negative results common to both sonographic criteria. The first patient was a one-year-old boy with high anorectal malformation and crossed fused renal ectopia who had right Grade II reflux on MCU The second patient was a ten-month-old boy with a high anorectal malformation whose right kidney was not visualized at sonography. MCU revealed a grade III reflux into a low-lying dysplastic right kidney. The inability to detect reflux in these patients can be explained by the technical difficulty involved in sonographic visualization of a malrotated or malpositioned kidney, especially when it is associated with dysplasia or reflux nephropathy [Figure - 3].
Criterion I gave three additional false negative results. Two of these patients had gross left hydroureteronephrosis [Figure - 4]. No further dilatation was observed during injection although moving microbubbles were clearly visualized. Both showed Grade V reflux on MCU.The third patient had a compact PCS on baseline sonography [Figure - 5]. ECS showed air bubbles in the PCS without accompanying dilatation and grade III reflux was seen on MCU. We believe that increase in dilatation alone is not a reliable sonographic sign in both grossly dilated and compact systems. Visualization of moving microbubbles is confirmatory for reflux in these cases.
Limitations of the study
In this study, sonographic evaluation of VUR was performed during the filling phase only. Therefore reflux occurring only during voiding could be missed by this technique. A very rapid and forceful injection of air during ECS may cause pain to the patient. Care should therefore be taken that the injection of air is slow, gentle and not more than 5-10 ml per 5-7 seconds. Commercially prepared, stable, echogenic contrast media are now available to overcome this disadvantage . Cystosonography necessitates urethral catheterization, which may be an unpleasant procedure for the child. To obviate the need for instrumentation. Color Flow Dopper sonography is currently being evaluated as an alternative . Grading or reflux is difficult with this technique and no standard grading system is as yet available. Also, the delineation of bladder and urethral anatomy is poor as compared to MCU. The technique is highly operator dependent and the development of expertise involves a learning curve.
We conclude that ECS using agitated saline is a sensitive, accurate and safe procedure for the detection of VUR. The visualization of moving microbubbles within the collecting system is a definitive sonographic sign of reflux. The observation of increase in dilatation alone should however be viewed with suspicion. We maintain that for the initial evaluation of children with a suspicion of reflux, there is as yet no satisfactory replacement for MCU to diagnose and grade reflux and to reliably demonstrate bladder and urethral anatomy  The absence of exposure to radiation is an advantage of cystosonography over MCU in the pediatric population. We recommend its use for the periodic follow-up imaging in children on conservative management, for the evaluation of success of surgery and for sibling screening.
We are grateful to the departments of Pediatric Surgery and Radiodiagnosis at the Post Graduate Institute of Medical Education and Research, Chandigarh for making this study possible.
| References|| |
|1.||Schultz FW, Geleijns J. Holscher HC, et al. Radiation burden to pediatric patients due to micturating cystourethrography examinations in a Dutch children's hospital. Br J Radiol 1999;72:763-772, |
|2.||Seppanen U, Torniainen P, Kiviniitty K. Radiation gonad doses received by children in intravenous urography and micturition cystourethrography. Pediatr Radio 1979; 8"169-172. |
|3.||Dimitrious P, Fretzayas A, Nicolaidou P, et al. Estimates of dose to the bladder during direct radionuclide cystography. J Nucl Med 1984; 25: 792-795. |
|4.||Blane CE, DipIetro MA, Zerin JM, et al. Renal sonography is not a reliable screening examination for vesicoureteral refolux. J Urol 1993; 150: 752-755. |
|5.||DiPietro MA, Blane CE. Zerin JM. Vesicoureteral reflux in older children: concordance of US and voiding cystourethrographic findings. Radiology 1997; 205: 821-822. |
|6.||Evans ED, Meyer JS, Harty MP, Bellah RD. Assessment of increase in renal pelvic size on post-void sonography as a predictor of vesicoureteral reflux. Pediatr Radiol 1999;29:291 -294. |
|7.||Craig JC, Knight JF, Sureshkumar P, et al. Vesicoureteric reflux and timing of micturating cystourethrography after urinary tract infection. Arch Dis Child 1997; 76: 275 - 277. |
|8.||Mc Donald A, Scranton M, Gillespie R, et al. Voiding cystourethrograms and urinary infections: how long to wait? Pediatrics 2000; 105:E50 |
|9.||Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of Vesicoureteric reflux. Pediatr Radiol 1985; 15:105-109 |
|10.||Tremewan RN, Bailey RR, Little PJ, et al. Diagnosis of gross vesicoureteric reflux using ultrasonography. Br J Urol 1976; 48:431-435 |
|11.||Kessler RM, Altman DH. Real-time sonographic detection of vesicoureteral reflux in children. Am J Roentgenol 1982; 138: 1033-1036 |
|12.||Schneider k, Jablonski C, Wiessner M, et al. Screening for vesicoureteral reflux in children using real-time sonography. Pediatr Radiol 1984; 14: 400-403. |
|13.||Hanbury DC Coulden RA, Farman P, Sherwood T., Ultrasound cystography in the diagnosis of vesicouereteric reflux. B J Urol 1990; 65: 250-253. |
|14.||Atala A, Wible JH, Share JC, et al. Sonography with sonicrated albumin in the detetion of vesicoureteral reflux. J Urol 1993; 150: 756-578. |
|15.||Bosis M, Cystosonography with echo contrast: a new imaging modality to detect vesicoureteric reflux in children. Pediatr Radiol 1998 ; 28: 250 - 255. |
|16.||Atala A, Ellsworth P, Share J, et al. Comparison of sonicated albumin enhanced sonography to fluoroscopic and radionuclide voiding cystography for detecting vesicoureteral reflux. J Urol 1998; 160 : 1820-1822 |
|17.||Darge K, Troeger J, Duetting T, et al. Reflux in young patients: comparison of voiding US of the bladder and retrovesical space with echo enhancement verusus voiding cystourethrography for diagnosis. Radiology 1999; 210: 201-207. |
|18.||Mentzel HJ, Vot S, Patzer L, et al. Contrast-enhanced sonography of vesicoureterorenal reflux in children: preliminary results. Am J Roentgenol 199; 173: 737- 741. |
|19.||Nasrallah PF, Nara S, Crawford J. Clinical applications of nuclear cystography. J Urol 1982; 128: 550-553 |
|20.||Dikshit MP, Acharya VN, Shikare S, et al. omparison of direct radionuclide cystography with micturating cystourethrography for the diagnosis of vesicoureteral reflux and its correlation with cystoscopic appearances of ureteric orifices. Nephrol Dia Transplant 1993; 8: 600 - 602. |
|21.||Chapman SJ, Chantler C, Haycock GB. Radionuclide cystography in vesicoureteric reflux. Arch Dis Child 1988; 63: 650 - 651. |
|22.||Jequier S, Jequier JC. Reliability of voiding eystourethrography to detect reflux. Am J Roentgenol 1989; 153: 807 - 810. |
|23.||Oak SN, Kulkarni B, Chaubal N. Color flow Doppler sonography: a reliable alternative to voiding cystourethrogram in the diagnosis of vesicoureteral reflux in children. Urology 1999; 53: 1211-1214. |
|24.||Hellstrom M, Jacobsson B. Diagnosis of vesico-ureteric reflux. Acta Paediatr Supple 1999; 88: 3-12. |
701, Cheviot Court, Freeman hospital, High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom
Source of Support: None, Conflict of Interest: None
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2]