# Radiation Safety and Future Innovative Diagnostic Modalities

Authors: Christian Radmayr
Journal: Advances in Urology
 (2008)

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## Abstract

One must demand an accurate, safe, radiation-free, and noninvasive method for reflux examination as the ideal possibility for reflux screening. Of course the available different imaging modalities are far from this ideal situation, but minimal radiation exposure is indeed a permanent objective. Additionally since all of these studies might be quite stressful to the child and the family, a specially designed and equipped environment is obligatory for the comfort of all involved. An absolute ideal modality in the diagnosis of VUR would be the definition of a certain marker in serum or urine that could identify children with VUR without the need for any interventional screening modality. Therefore more and more efforts have to be made in the future to investigate different markers for this purpose. Since reflux is one of the most frequent congenital conditions pediatric urologist have to deal with potential risks that might lead to renal insufficiency, noninvasive and radiation-free modalities should become the methods of choice, hopefully in the near future.


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## Body

## 1. Introduction

Different
imaging  modalities  for evaluating vesicoureteral reflux (VUR) are nowadays
available and more and more attention is paid to concerns about radiation
safety, especially when multiple imaging studies are necessary with repeat
exposition to ionizing radiation during a conservative follow up. Minimal
radiation exposure is now a permanent objective.Experience
and logistic availability are often responsible for choosing the one or the
other imaging study. Moreover, patient age, gender, race, and parental
preference and anxiety about invasiveness and radiation exposure play an
additional role as well.In
the past years, different innovative techniques like low-dose fluoroscopy have
definitively decreased radiation dose to the patient. On the other hand,
diagnostic quality images are mandatory for appropriate diagnosis and
treatment. Ultrasonography, nuclear medicine, and magnetic resonance are
preferred to intravenous urography and computed tomography whenever possible.
In general, voiding cystourethrography has frequent indications in pediatric
urology and efforts are made to replace it by radionuclide cystograms or
sonocystograms in order to reduce the exposure to ionizing radiation.Furthermore,
there is also no consensus about the timing of evaluation for possible reflux
as well as in the conservative follow up or after intervention.


## 2. Voiding Cystourethrograpy, Radionuclide Cystography, Sonocystography

All
these three modalities can be used to demonstrate the presence or absence of
VUR. Voiding cystourethrograpy (VCUG) as well as direct radionuclide
cystography (RNC) are invasive diagnostic tools with the need for patient
preparation and catheterization and the exposition of the patient to ionizing
radiation although VCUG is a fluoroscopic examination and RNC a nuclear
medicine study, respectively. Additionally, an indirect RNC with the
intravenous administration of technetium-99m-labeled diehtylenetriamine
pentaacetic acid is a possible tool with the assumption of a possible VUR when
radioisotope counts increase in the renal areas after voiding. But the false
negative rates may vary between 22 to 51% [1].Even
though being invasive as well since catheterization is mandatory, the big
advantage of performing a sonocystography is the prevention of any ionizing
radiation to the patient at all.For
a conventional VCUG, a water soluble contrast medium is instilled into the
bladder after preparation and transurethral sterile catheterization. An option
is the suprapubic administration of the contrast, but still invasive. Different
fluoroscopic images are taken to demonstrate the presence or absence of
vesicoureteral reflux.The
same procedure (preparation and catheterization) is necessary for performing an
RNC. Usually technetium 99m pertechnetate is the radiopharmacon of choice to be
instilled into the bladder. The radioactive emissions are continuously recorded
with a gamma camera.When
comparing these two wide spread diagnostic modalities, the big advantages of a
classical VCUG are the provision of high-resolution images with a clear
evaluation of the bladder wall, the urethra especially in males [2],
any sign of intrarenal reflux as well as a clear grading possibility. It is
also supplementary reliable for detecting duplication, ureteral ectopia with or
without ureteroceles, and posterior urethral valves. That is why especially in
boys and also for the initial investigation in girls a classical VCUG is still
the preferred method of choice by many investigators. On the other hand, the
expense is a much higher dose of ionizing radiation to the patient.Although
recent improvements introducing low-dose fluoroscopy techniques and pulse
fluoroscopy with the add of digital enhancing modalities have decreased the
radiation dose to the patients dramatically [3–5],
still a VCUG exposes the patient to almost 100 times the radiation of an RNC. A
special concern is the quite high gonadal radiation dose particularly with
multiple studies of fluoroscopic monitoring [6]. Of course gonadal shielding in
males and careful imaging coning help to decrease the patient’s radiation
exposure. Moreover, with the use of a low-dose fluoroscopic system in
conjunction with a computer-based video frame grabber, the ovarian radiation
dose may become comparable to RNC [3]. A VCUG performed with an
optimized pulsed fluoroscope can achieve “as low as reasonably achievable” (ALARA)
levels and of course maintain diagnostic image quality. With such a setting
radiation dosage can be reduced to 10% that of continuous fluoroscopy thus
resulting in dosages at about 10 times that of RNC. Therefore, pulsed
fluoroscopy is currently the recommended standard [7, 8].On
the other hand, a direct RNC allows continuous monitoring for VUR throughout
the whole examination time without any additional radiation introduced.
Therefore, some authors prefer RNC to be more sensitive in the diagnosis of VUR
[9] although precise grading is impossible. But this makes it probably an ideal
methodology for the conservative follow up and after any antireflux
intervention.The
main advantage of RNC over fluoroscopic VCUG is definitively decreased
radiation exposure of the patient. The average effective radiation dose of a
VCUG using low-dose fluoroscopy is around 3 mrem, compared to 0.5 mrem for an
RNC. Of course the average effective dose of the VCUG is variable and depends
on the patient size, operator, and machinery [8]. The sensitivity of
RNC for detecting reflux is equal to or even greater than that of VCUG;
however, the spatial resolution and anatomic detail seen on an RNC are
ultimately inferior to those seen on a VCUG [10].Sonocystography
may be used as a very sensitive tool in the detection of a possible VUR
especially since the intervention of various ultrasound echo enhancing agents
[11]. First, attempts with this technology have been made back in 1976. The
capability of echo-enhanced refluxsonography extends further in that
the method may enable complete eliminationof any radiation
exposure. This may justify the longer examination time compared with
that of VCUG. Using an X-ray contrast agent, a certain concentration
at a given time is necessary to be able to see the contrast, whereas
even single microbubbles can be visualized with the ultrasound method. This
together with the duration of the ultrasound examination as well might be
responsible for the detection of some low grade refluxes that might be missed
using VCUG and RNC. Moreover, this method allows for cyclic fillings without
any additional radiation as well. On the other hand, similar to RNC, the
lack of diagnostic visualization of anatomic details and particularly the
urethra represent a disadvantage of the ultrasound methodology. Additionally,
the interobserver variability might be quite high and a specially trained
examiner is obligatory. In summary, of the available literature on that issue,
the comparative aggregated data between sonocystography and VCUG indicate that
reflux exclusion and diagnosis between the two methods is highly concordant and
that the discordant findings are primarily due to more reflux episodes being
detected solely by sonocystography and that these reflux episodes are of higher
grade and consequently may be clinically more relevant than the predominantely
low grade reflux found only on VCUG and that finally the high negative
predictive value of sonocystography may have practical consequences as it
demonstrates that sonocystography may be suitable for screening purposes
[12, 13].


## 3. Conclusion and Future Modalities

One
must demand an accurate, safe, radiation-free, and noninvasive method for
reflux examination as the ideal possibility for reflux screening. Additionally,
since all of these studies might be quite stressful to the child and the family
a specially designed and equipped environment is obligatory for the comfort of
all involved. Preparation and education of the families help to reduce
discomfort. If needed, sedation with the use of midazolam can be beneficial
without any negative influence on the outcome of the examination [14].Contrast
enhanced ultrasound allows an accurate and safe diagnosis and is in addition to
VCUG and RNC radiation free as well; but unfortunately, still an invasive
procedure with the insertion of a catheter. A future prospective might be an
exogenous bubble generation to fulfil one of the most important criteria in
reflux diagnosis: being noninvasive. Efforts are already being made to achieve
this goal. Till then nuclear medicine studies and contrast studies will remain
essential for the evaluation of VUR.An
absolute ideal modality in the diagnosis of VUR would be the definition of a
certain marker in serum or urine that could identify children with VUR. Basic
research is going on to investigate different markers that have been found to
be elevated in children with VUR [15]. Measured levels of microproteinuria,
urine retinol-binding protein, urinary prostaglandine E2, urinary β2-microglobulin,
urinary interleukin levels, and serum endothelium leukocyte adhesion molecule
have been shown to be elevated in patients with VUR compared to controls. So
far, none of these methods can localize which kidney is affected by reflux nor
can they assess the grade but they probably offer the potential advantage of
rapidly screening for VUR.Another
marker,β-hexosaminidase, has been shown to be higher
in patients with VUR and renal scarring [16]. Tamm-Horsefall protein (THP) is
another high-molecular-weight glycoprotein that is exclusively present in the
kidney and not secreted elsewhere. In children with intrarenal reflux, it is
also detectable in blood vessels and lymph nodes. It is believed to accumulate
from leakage of adjacent ruptured tubules [17]. Interestingly, in a study on
children with surgically corrected VUR but no improvement on renal function
postoperatively, THP levels remained elevated before and after surgery [18]. Still
a lot of research has to be undertaken to minimize or hopefully abandon the
burden of one of the widest used imaging modalities in pediatric urology.



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*Source: 827106-2008-06-04.xml*