State-of-the-Art Renal Imagingin ChildrenBernarda Viteri, MD,a,b,c Juan S. Calle-Toro, MD,b Susan Furth, MD,a,c Kassa Darge, MD,b,c Erum A. Hartung, MD,a,c
Hansel Otero, MDb,c
abstractImaging modalities for diagnosing kidney and urinary tract disorders inchildren have developed rapidly over the last decade largely because ofadvancement of modern technology. General pediatricians and neonatologistsare often the front line in detecting renal anomalies. There is a lack ofknowledge of the applicability, indications, and nephrotoxic risks of novelrenal imaging modalities. Here we describe the clinical impact of congenitalanomalies of the kidneys and urinary tract and describe pediatric-specificrenal imaging techniques by providing a practical guideline for the diagnosisof kidney and urinary tract disorders.
Renal imaging continues to evolverapidly. From advances in conventionalkidney ultrasound to quantitativeimaging evaluation, new technologiesare transforming how we assess kidneyfunction and disease. Congenitalanomalies of the kidney and urinarytract (CAKUT) are the most commoncause of end-stage renal disease inchildren and, consequently, the mostcommon cause of the need for renalreplacement therapy, such as dialysis,in this patient population.1,2 As a result,imaging is crucial for early detection ofkidney and urinary tract disease,monitoring of kidney function, andenhancing the assessment of diseaseprogression and prognosis.Conventional methods for the diagnosisof renal dysfunction based on clinicalchemistry measurements (such asserum creatinine level) have beenshown to be suboptimal for earlydetection of functional loss.3
CAKUT includes a variety of disordersthat arise during the development ofthe kidneys, ureters, bladder, andurethra in fetal life. Although CAKUTtends to present sporadically,associated anomalies have beendescribed in up to 30% of infants born
with CAKUT.4 CAKUT constitutes 20%to 30% of all anomalies identified in theprenatal period and occurs in up to60% of children with chronic kidneydisease (CKD) in the postnatalperiod.1,2,5 Common types of CAKUTresult from failure of normal nephrondevelopment (renal dysplasia, renalagenesis, and multicystic renaldiseases), abnormalities of embryonicmigration of the kidneys (ectopickidneys and horseshoe kidneys), andabnormalities of the developing urinarycollecting system (vesicoureteral reflux[VUR], ureteropelvic junctionobstruction, lower urinary tractobstruction, etc). CAKUT often presentswith urinary tract dilation (UTD),previously referred to ashydronephrosis.6,7
Although hydronephrosis remainsa commonly used term, it often hasdifferent meanings amongpractitioners. In 2014, a unifiedconsensus reached among multipleprofessional societies recommendedreplacing the term hydronephrosis withthe more specific descriptor UTD todenote an imaging finding in a systemthat may or may not be under pressure(ie, obstructive versus nonobstructive
aDivision of Nephrology, Department of Pediatrics andbDivision of Body Imaging, Department of Radiology,Children’s Hospital of Philadelphia, Philadelphia,Pennsylvania; and cDepartment of Pediatrics, PerelmanSchool of Medicine, University of Pennsylvania, Philadelphia,Pennsylvania
Drs Viteri and Otero conceptualized and designedthe manuscript, coordinated data and imagescollection, analyzed data, and drafted and revisedthe final manuscript; Drs Darge and Furthcontributed to the design of the manuscript andcritically reviewed the manuscript for importantintellectual content; Drs Calle-Toro and Hartungparticipated in the design of the manuscript andcritically reviewed the manuscript for importantintellectual content; and all authors approved thefinal manuscript as submitted and agree to beaccountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2019-0829
Accepted for publication Aug 5, 2019
Address correspondence to Bernarda Viteri, MD,Division of Nephrology, Department of Pediatrics,Children’s Hospital of Philadelphia, 3500 Civic CenterBlvd, Buerger Center, 9th Floor, Philadelphia, PA19104. E-mail: [email protected]
FINANCIAL DISCLOSURE: The authors have indicatedthey have no financial relationships relevant to thisarticle to disclose.
FUNDING: Supported by National Institutes of Healthgrant T32DK007006 (principal investigator LawrenceHolzman). Funded by the National Institutes of Health(NIH).
POTENTIAL CONFLICT OF INTEREST: The authors haveindicated they have no potential conflicts of interestto disclose.
To cite: Viteri B, Calle-Toro JS, Furth S, et al.State-of-the-Art Renal Imaging in Children.Pediatrics. 2020;145(2):e20190829
PEDIATRICS Volume 145, number 2, February 2020:e20190829 STATE-OF-THE-ART REVIEW ARTICLE
UTD).8 Antenatal and postnatal UTDeach have their own scoring systemfor reference (Fig 1).8 Higher scoresrelate to a higher degree of dilatationand renal parenchymal, ureteral, and/or bladder abnormalities that requirefurther workup and monitoring.9
There is currently no single goldstandard to assess obstructiveuropathy in children, and usually,a combination of imaging tests areused.10–12 Although renal bladderultrasound, fluoroscopy, and nuclearmedicine functional studies remainthe main tools for anatomic andfunctional diagnosis and managementof UTD and CAKUT, noveltechnologies have been added to the
armamentarium of pediatric renalimaging. Emerging technologies thatare increasingly being used in clinicalsettings include functional magneticresonance urography (fMRU),contrast-enhanced ultrasound(CEUS), and contrast-enhancedvoiding ultrasound, which candelineate anatomy at a higherresolution and provide functional,perfusion, and excretion informationof the kidneys and urinary tractwithout using ionizing radiation.Additional techniques that remainunder study include three-dimensional (3D) printing,elastography, and volumetric analysis.Our purpose for this article is toprovide a comprehensive overview of
renal imaging modalities with anemphasis on novel techniques andtheir potential clinical value in thedetection and monitoring of childrenwith kidney disease.
ANATOMIC IMAGING
Ultrasound
Renal and bladder ultrasound (RBUS)is the first-line imaging modality forevaluation of the renal anatomy inchildren because it is noninvasive, isbroadly available, is relatively fast,lacks ionizing radiation, and is lesscostly than other imaging modalities.Additionally, ultrasound does notrequire specific patient positioning orthe need to be in a machine, whichallows for imaging of children whilein supine, prone, semi-upright orupright positions or, in the case ofinfants, while being held bya caregiver. RBUS depicts kidney size(and growth over time), echogenicity,echotexture, parenchymal thickness,the duplex system, and the degree ofdilatation of the pelvocalyceal systemand ureters in children.13 RBUS canbe used to identify masses and largecalculi, can be used to measure pre-and postvoid bladder volumes, andcan provide real-time images forguidance of interventionalprocedures.
During basic ultrasound imaging, thekidney may be divided into an outercortex and an inner medulla. Thecortex is composed of an outer rim oftissue as well as columns of corticaltissue that descend between themedullary pyramids (Fig 2A). Thesecolumns have been termed the septalcortex, also commonly referred to ascolumns of Bertin (Fig 3). Themedulla is composed of a variablenumber of renal pyramids, with thebase of the pyramid formed by itsoverlying renal cortex and its apex bythe renal papilla that projects intoa minor calyx. The papillae are cone-shaped structures that contain theopenings of the collecting ducts,which empty into the calyces. A calyx
FIGURE 1Postnatal UTD classification and recommendations with grayscale ultrasound representativeexamples. Postnatal presentation for UTD P1, low risk; UTD P2, intermediate risk; UTD P3, high risk.Classification is based on the most significant ultrasound finding. For example, if the anterior-posterior renal pelvis diameter is found within UTD P1 range, but there is peripheral calycealdilation, then the correct classification is UTD P2. a Calyceal dilation and ureteral dilation are oftenpresent in patients with UTD P3 but are not needed to qualify for UTD P3 if there is UTD with eitherabnormal parenchymal thickness, abnormal parenchymal appearance, or abnormal bladder.Adapted from Nguyen HT, Benson CB, Bromley B, et al. Multidisciplinary consensus on the classifi-cation of prenatal and postnatal urinary tract dilation (UTD classification system). J Pediatr Urol.2014;10(6):982–998 and Chow JS, Koning JL, Back SJ, Nguyen HT, Phelps A, Darge K. Classification ofpediatric urinary tract dilation: the new language. Pediatr Radiol. 2017;47(9):1109–1115.
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is a cup-shaped portion of theintrarenal collecting system. Thecalyces, infundibula, and renal pelvisare jointly referred to as theintrarenal collecting system.14
Novel technologies can now provide3D images with higher spatial andcontrast resolutions compared withprevious 3D modalities.15 Clearer andsharper ultrasound images (withfewer artifacts) allow accuratereconstructive analysis of the
anatomy (Fig 4), better tissuedifferentiation (eg, fluid-filledstructures), and improvedidentification of echo-enhancingstructures, such as renal stones andrenal parenchymal lesions.16,17 Onehas to be cautious in interpretinghigher-resolution images, however,because the corticomedullarydifferentiation can be overlyenhanced and may falsely mimicnephrocalcinosis.18
Three-dimensional ultrasound(3DUS) provides volumetricevaluation and more completevisualization of the collecting system,
and it decreases imaging time byrequiring a single sweep withreconstruction in multiple planes ata later time.19,20 Therefore, interestnow lies in supporting quantitativeimaging analysis, such as automatedsegmentation of the kidneys andurinary tract, to enhance the care ofchildren with UTD.
Given parenchymal volumecalculations from 3DUS arecomparable to those fromdimercaptosuccinic acid scintigraphyand magnetic resonance urography(MRU), its emergence can result indecreased use of computedtomography (CT), MRI, and diureticrenography.21,22 Similarly, high-quality 3DUS depiction andsegmentation of the collecting system,which may have the potential tobetter reveal complex anatomy, mayresult in decreased need forfluoroscopic evaluation of thecollecting system or MRU.Additionally, 3DUS providesa multiaxial demonstration of theentire kidney.15,16
Shear-wave elastography is anotheradvance in ultrasound technologythat is a noninvasive way to assesstissue stiffness.23,24 The ultrasoundtransducer sends an acoustic waveinto the tissue to create a wave oftissue displacement. Tissue stiffnessderives from the speed at which thedisplacement wave traverses the
FIGURE 2A and B, Normal renal anatomy of the right kidney as seen on sagittal grayscale and CEUS in a 13-month-old girl with febrile UTI.
FIGURE 3A, Grayscale ultrasound in an 8-year-old girl with day wetting reveals a normal left kidney with a prominent column of Bertin, which is a common normalvariant that could be mistaken for a lesion (renal pseudotumor) because, as delineated in B, it interrupts or splits the normal renal sinus. Sag, sagittal.
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tissue, as measured by a secondultrasound pulse (Fig 5). Thismodality has been more broadlystudied in the liver (eg, to measurefibrosis in autosomal-recessive
polycystic kidney disease), thyroid,breast, gastrointestinal tract, andprostate.23,25 More recently,elastography has been investigated inthe kidney to measure fibrosis and
changes in tissue stiffness in CKD,kidney allografts, and VUR. Furthercharacterization of focal renal lesionsis another applicability in whichelastography is being studied.26
New two-dimensional ultrasoundtechnologies now includesemiautomatic quantification of UTDseverity.27 For this, postprocessingimaging software uses the ultrasounddata to calculate multiple parameters,such as size of the collecting system,depth of calyces, thickness ofparenchyma, geometric shape,circularity ratio, and curvedescriptors. An algorithm then usesthese measurements to identify thosepatients who will benefit from renalfunction tests (ie, diureticrenography), saving theinconvenience, risks, and nonrequiredionizing radiation of additionaltesting on those who do not meetcriteria.27
CEUS
CEUS is an innovative imagingmodality that uses nonnephrotoxicmicrobubbles (gas core with a lipidmonolayer stabilizing shell no biggerthan a red blood cell) as anintravenous (IV) ultrasound contrastagent (UCA), as seen in Fig 2B. UCAsare currently approved by the USFood and Drug Administration for IVuse in cardiac and hepaticultrasounds and for intravesical usefor the evaluation of VUR in children.Despite being off label in the UnitedStates, its renal applications havegrown in recent years.28 CEUS hasbeen shown to be more sensitive indetecting perfusion abnormalitiesthan Doppler (Fig 6). This is due tothe ability of CEUS to enhance thevascular echo signal through the useof a purely intravascular contrastagent rather than by detecting theDoppler shift, which is highlydependent on many technical factors,such as speed of acquisition, angle ofimaging, depth of imaging, andfrequency.29 CEUS in clinical practiceprovides dynamic information, such
FIGURE 43DUS scanning of the left kidney. A, After a single automatic “sweep” in the sagittal plane (red box). Band C, Additional axial (green box) and coronal (blue box) images can be reconstructed from theoriginal sagittal images in this 7-year-old girl with a right renal mass (not shown).
FIGURE 5Ultrasound shear-wave elastography of the left kidney in a 3-year-old with cerebellar vermis hypo/aplasia, oligophrenia (mental retardation), ataxia, ocular coloboma, and hepatic fibrosis syndromereveals normal renal stiffness (velocity 2.39 m/second). The elastography samples the tissue insidethe box, and its value is expressed as the velocity of the wave through the tissue (Vs) (ie, measuringthe velocity of a vibration wave generated from the probe on the skin of the patient).
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as perfusion of the microvasculatureof the kidney and, potentially, thequantification of renal blood flowas well as additional perfusioncharacteristics of masses andcystic lesions.30–32 In kidneytransplantation, CEUS has been ableto detect early features of allograftdysfunction in the setting of acutetubular necrosis, rejection, corticalnecrosis, and other vascularcomplications.33–35 A small-sampleadult study revealed that CEUS mightbe a good prognostic markerreflecting microvascularcharacteristics of the kidney allograftitself, independent of the vasculatureof the recipient.36 Consequently, itmay be a nonimmunologic predictorof long-term kidney allograft function.
Performance of CEUS usually involvesat least 2 people: the scanneroperator in charge of imageacquisition and a second member (eg,nurse, sonographer, or radiologist)responsible for the contrast IVadministration. With a single
injection, one can obtain images ofa lesion or region of interest, 1(Fig 2B) or both kidneys. Repeatingthe initial dose 1 time will allow oneto obtain “first-pass” images for eachkidney separately. First-pass imagesrepresent the initial contrast flowfrom the arteries into the renal cortexand, subsequently, the parenchyma asopposed to equilibrium or washoutimages, which refer to later images inwhich the contrast diffuses into thepyramids and later reabsorbs.Postacquisition quantification ofperfusion or relative enhancement is,to date, a work in progress with nostandardization but promisingpreliminary results.37,38
Voiding Cystourethrography
Fluoroscopic voidingcystourethrography (VCUG) is thegold standard for diagnosing andgrading VUR and is used to evaluatethe bladder and urethra in detail aswell. VUR is suspected on the basis ofUTD, ureteral dilatation, an abnormal
RBUS (such as uroepithelialthickening or scarring) after firstfebrile urinary tract infection (UTI),recurrent UTI, dysfunctional voiding(such as neurogenic dysfunction ofthe bladder), and bladder outletobstruction, among others. It isimportant to note that in somecircumstances, a retrogradeurethrogram, in which only theurethra is imaged, may be preferredover a VCUG, particularly in childrenwith trauma or dysuria. By usinga bladder catheter, iodinated contrastmaterial is instilled into the bladder,and pulsed fluoroscopy, the last imageheld, or the fluoroscopic screencapture (which results in a muchlower radiation dose) is obtained. Keyimages are as follows: (1) an early-filling, last-image capture of thebladder, which may reveal anintravesical ureterocele or othermasses; (2) early oblique views; (3)oblique radiographs of the bladder atfull capacity before voiding; (4)images of the urethra during voidingbefore and after removal of thecatheter (lateral for male patients andfrontal for female patients); and (5)images of the renal fossaeimmediately after voiding todocument the presence and grade ofreflux or its absence. Cyclical filling ofthe bladder (filling to capacityfollowed by voiding and refilling fora second or third time) is helpful ininfants (1 year of age or younger)who void at low volumes.39
Contrast-Enhanced VoidingUrosonography
Contrast-enhanced voidingurosonography (CeVUS) is anultrasound-based, radiation-freealternative to evaluate for VUR orurethral pathology.40,41 CeVUS usesan UCA, and, like in VCUG, thecontrast is administered via a bladdercatheter. When compared with VCUG(Fig 7), CeVUS has been shown to bemore sensitive in detecting VUR, witha higher grade of reflux in up to two-thirds of patients, and has beenshown to be as good for the
FIGURE 6Ultrasound images on day 2 after right lower-quadrant transplant of allograft kidney in a 15-year-oldgirl revealing hypoperfusion to lower pole. A, Color Doppler. B, Power Doppler. C, CEUS (whitedelineation highlights hypoperfused lower pole region).
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evaluation of the urethra.42,43 CeVUSis performed by using an ultrasoundscanner, which is smaller and morepediatric friendly than a fluoroscopysuite. It can be performed in differentpositions (eg, scanned from the backwhile sitting or standing) whilecaregivers are holding their childrenor are nearby. Similar to VCUG, thebladder is filled under ultrasoundmonitoring, followed by alternatescanning of the right and left kidneysand the bladder. During voiding,additional urethral suprapubic and/or transperineal scans are performedwith the catheter in place, and aftercatheter removal, additional postvoidscans are performed. The detection ofmicrobubbles within a ureter or renalcollecting system indicates VUR,which is graded similarly in VCUG.44
As with VCUG, cyclical filling may benecessary in neonates and infants.UCAs have a good safety profile forintravesical use, with no known sideeffects.40
CeVUS involves 2 team members withsimilar tasks, as described for CEUSperformance (see previous section);however, similar to VCUG, thesupervising radiologist remains in theroom during the entire procedure.CeVUS has the potential of replacingsome of the clinically indicated VCUG
and will be incorporated asan equivalent test with thesame indications in the 2019revision of the American Collegeof Radiology–Society of PediatricRadiology Practice Parameter for thePerformance of VoidingCystourethrography in Children (K.D.,personal communication, 2019).Moreover, in therapeutics,intraoperative applicability ofCeVUS has improved Defluxinjection success rates, withincreased resolution of VUR by∼20%.45
3D Printing
In 2013, the Radiologic Society ofNorth America launched a programon 3D printing that included thefabrication of organs as depicted onCT and magnetic resonance (MR)images, which included an excellentdelineation of kidney morphology.Since its introduction, newer 3Dprinting formats have been developedto incorporate surface texture, color,and material properties into themodels.46 These 3D-printed modelsare patient specific and serve asinnovative presurgical andpreintervention tools. In renaldisease, 3D models have revealedhigh accuracy in replicating complex
anatomic structures andpathologies.47,48 Models of thekidneys with renal tumors have beenreported to enhance theunderstanding of surgeons,trainees, and patients and theirfamilies regarding the goals ofsurgery.46–51 This has generated animprovement in patient educationand satisfaction.51 As surgicalapproaches evolve from traditionalopen to minimally invasiveapproaches, 3D printing becomes anincreasingly valuable surgicalplanning and simulation tool.49,52,53
As the technology expandsand becomes more broadlyavailable, it may become standard ofcare, especially in complexanatomic cases.
CT
CT allows for high anatomicdefinition and provides a panoramicimage of the kidney and urinarytract. It is a fast and volumetric (ie,the size of pixels is similar in allplanes, and hence pixels arecommonly referred to as “voxels”)imaging modality that allows for 3Dand multiplanar reconstructions inall planes. Postprocessing can usethe raw data as the base for 3D-printed models. CT is the mainimaging modality for evaluatingrenal pathology in adults but isless preferred in pediatrics becauseof lower incidence of stones andmalignancies in children and to avoidionizing radiation exposure.54,55 Inchildren, CT without contrast is therecommended imaging modality forevaluation of suspected urolithiasisafter an equivocal ultrasound fortreatment planning of known casesof urinary stones and intraumatic hematuria.56 CTangiography is used to evaluatesuspected renovascularhypertension as an alternative toDoppler ultrasound or MRangiography (Fig 8). Whena contrast-excretion phase isincluded in the CT examination, it iscalled CT urography (Fig 9), which is
FIGURE 7A and B, Right grade 4 VUR on a 1-month-old girl on VCUG without significant interval change,compared with CeVUS (image reconstructed to ease comparison) at 2 years of age.
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useful in the evaluation oftrauma, suspected urinary tractobstruction, or calyceal diverticula.57
Although CT IV iodinated contrastagents are generally safe, there isa possible risk of postcontrast acutekidney injury (PC-AKI).58–60 PC-AKIincidence was reported at 10% ina small cohort of children.61
However, PC-AKI is a correlativediagnosis that has been challengedmore recently.62 The association, orlack thereof, between CT iodinatedcontrast administration and PC-AKIin children is yet to be established;moreover, a newer generation of CTscanners allows for lowerradiation doses.
FUNCTIONAL IMAGING
Functional Renogram
Nuclear medicine functional renalscans follow the uptake and excretionof radiotracers, also calledradiopharmaceutical agents, throughthe kidneys and into the collectingsystem. Unlike other imagingmodalities that rely on an externalradiograph source, nuclear medicinescanners capture g-rays emitted fromthe patient’s body after radiotraceradministration, hence reflecting thedistribution of radiotracers in thepatient and expressed in countsover time. Some variations in thenomenclature and protocol exist, and
these studies are also referred to asfurosemide renography, renalscintigraphy, radionuclide renalscintigraphy, diuretic renography,radioisotope renography, and nuclearmedicine renogram. The study canbe completed by using differentradiotracers classified by theiruptake and clearance mechanismsas agents for glomerularfiltration (99mTc-labeleddiethylenetriaminepentaacetic acid[DTPA]), tubular secretion (99mTc-labeled mercaptoacetyltriglycine[99mTc-MAG3]), or cortical tubularbinding (99mTc-labeleddimercaptosuccinic acid [99mTc-DMSA]).10,63–65
In the dynamic function of renalscans, the renal blood flow is firstevaluated immediately after IVinjection of the radiotracer bolus,after the first pass of the tracer to thekidney. Then the uptake andclearance function are assessed overthe next 20 to 30 minutes in 10- to20-second frames.10,65 Whenincomplete radiotracer drainage leadsto concern of urinary tractobstruction, a loop diuretic is givenand a second series of images isacquired for an additional 20 to30 minutes while the bladderempties. These images help calculatea filtration rate that providesinformation regarding how well the
FIGURE 8Bilateral renal artery stenosis in a 4-year-old with systolic blood pressures in the 200s who wassubsequently diagnosed with fibromuscular hyperplasia. A and B, CT images and angiography reveallong-segment severe stenosis of the right renal artery near the aortic origin and a shorter segmentof severe stenosis on the left, both sides with poststenotic dilatation.
FIGURE 9Normal renal anatomy as seen in CT urography in a 14-year-old boy. A, Coronal noncontrast CT image reveals the outline of the kidneys and is useful inidentifying stones and calcifications (when present). B, Coronal CT postcontrast image by using a split-bolus technique (which allows for the evaluation ofthe renal cortex and collecting system in a single set of images) reveals the normal enhancement of the cortex as well as the contrast within thecollecting system, properly delineating the calyces (yellow arrow) and renal pelvis (magenta star).
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kidney is functioning and if thereis an obstruction.65 These imagesare used to calculate the clearancerate of the radiotracer, which ismeasured as washout half-time. Inpatients with difficulty emptyingthe bladder, such as infants, orpatients with neurogenicbladder, placement of a urinarycatheter is recommended beforeinitiation of the study so thatresults can be analyzed in anotherwise unobstructed outletsystem.10,65 It is importantto note the residual urinevolume can be measured as pre- andpostvoid bladder counts.66
Mercaptoacetyltriglycine andDTPA are rapidly taken up by thekidney via different mechanisms andlater excreted via the urinary tract.DTPA is freely filtered byglomeruli and is not secreted orreabsorbed by the tubules beforebeing excreted. Hence, it can beused to measure the glomerularfiltration rate by quantifyingthe amount of filtrate formedper minute.10,63,64
Mercaptoacetyltriglycine is notfiltered through theglomerular membrane, and itsextraction requires delivery of thecompound to the kidney (renalplasma flow) and extractionfrom the plasma (renal tubules).Hence, clearance ofmercaptoacetyltriglycine isexpressed as the effective renalplasma flow, an approximation ofrenal plasma flow (unadjusted byspecific extraction and filtrationfactors) (Fig 10).67 99mTc-DMSAbinds to the cortical tubules, and itremains in the renal parenchyma foran extended period. Becausedimercaptosuccinic acidaccumulates in the functioningrenal cortex, the impaired renalcortex and space-occupying lesionsare revealed as hypoactive areas(Fig 11).10,63,65
Differential or “split” renal functionis calculated either by using the
number of counts produced fromeach kidney during the uptake phaseafter (contrast or radiotracer)injection or by using a graphicalanalysis technique (Rutland–Patlakmodel) and is expressed asa percentage of the sum of theright and left computedparameters. In subjects withnormal renal function, the 95%confidence interval for the relativeuptake of 99mTc-MAG3 ranges from42% to 58%.68 The spatialresolution (ie, the number ofpixels used to reconstruct an imageand, hence, a measure of the abilityof the image to discriminatebetween 2 adjacent structures) ofnuclear medicine studies is muchlower (10 mm in plane resolution)than the spatial resolution ofanatomic imaging modalitiessuch as ultrasound (0.1 mm),CT (0.5 mm), or MRI (1 mm).Hence, in patients with dilated renal
calyces and dilated renal pelvis,the postprocessing analysismight not be truly representativeof the area of functional interest(parenchyma only) but mayalso include the collectingsystem itself. Acknowledginga certain degree of inaccuracy,the renal size is determinedfrom the pixel length andarea of the whole kidney(Fig 10).63,69
Mercaptoacetyltriglycine renal scanhas multiple advantages, mostimportantly, because there isextensive clinical experience.Additionally, the radiotracers arenonnephrotoxic and without risk ofaccumulation or deposition in thebody.63 Disadvantages ofmercaptoacetyltriglycine renal scansinclude a lower spatial resolution andconcern about the use of radiation.However, the usual radiation dose
FIGURE 10A, Nuclear medicine renal scan with 99mTc-MAG3 of a 13-month-old girl with bilateral UTD at birth. B,The study reveals decreased uptake by the right kidney, with a differential renal function of 46% forthe right kidney and 54% for the left kidney.
FIGURE 1199mTc-DMSA renal scan in a 10-month-old girl with a history of right grade II and left grade III VURand recurrent UTIs. A, Cortical defects on the upper pole of the right kidney and midportion of theleft kidney. B, The differential renal function is 45% vs 55% for the left and right kidney,respectively.
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represents ,5% of the yearlyradiation dose considered safe forradiation workers.63,70 After3 hours, .95% of 99mTc-MAG3 leavesthe body in patients with normalkidney function, and patients can goto public places and use a bathroomwithout risk to exposing others toradiation.63
fMRU
fMRU provides a comprehensivemorphologic and functionalevaluation of the urinary tract ina radiation-free single examinationwith excellent spatial, contrast, andtemporal resolution and is thereforebecoming the test of choice inpatients with complex anatomy.fMRU depicts detailed anatomy ofthe genitourinary system, serving asa presurgical road map with a highlevel of confidence because itprovides a precontrast 3Dreconstruction. As part of theprotocol, patients receive IVhydration and diuretics (furosemide)before image acquisition for betterresolution. Similarly, the bladder isand should be catheterized toreduce the confounding effect ofdifficulty voiding and/or VUR. Forthe functional part of the study,a gadolinium-based contrast agentis administered steadily and imagesare acquired dynamically over time.The important clinical, functionalinformation obtained from analyzingcontrast flow dynamics allows forsome degree of confidence indifferentiating obstructed fromnonobstructed renal collectingsystems (Figs 12 and Figs 13).71
During the 8-minute high-resolution dynamic scan, theenhancement of the aorta, thekidneys, and, in most cases, theinitial drainage flow of the urinarysystem is obtained. PostprocessingfMRU-specific software is required toobtain quantitative parameters aswell as enhancement andexcretion curves. The most widelyused functional analysis software isa custom-made freeware known as
CHOP-fMRU (www.chop-fmru.com).72
The enhancement and excretioncurves are a display of the change ofsignal intensity over time and arecalculated for the aorta, renalparenchyma, pelvis, and calyceswith higher spatial resolution thannuclear medicine studies. Eachcurve represents the relativeenhancement of the segmentedregion of interest over time fromthe baseline (ie, precontrastsignal). The excretion curve is
focused on the change of signalintensity generated by thecontrast accumulation in thecollecting system. It is important tonote that an abnormallyprolonged renal transit time (thetime needed for the contrast agentto reach the ureter below the levelof the lower pole of the kidney) doesnot necessarily discriminatebetween ureteropelvicobstruction and the pooling of thecontrast agent in a dilated renalpelvis.72 Imaging with the patient inprone position helps to mitigate this
FIGURE 12Renal anatomy as seen in MRU. A, Coronal fluid-sensitive (heavily T2-weighted) MR image revealsa normal right kidney with low-signal intensity of the cortex (yellow star), intermediate-signalintensity of the medulla (white star) and high intensity (urine) within the normal calyces (whitearrow). The left kidney has a duplicated collecting system with markedly dilated central calyces inthe lower pole, which is obstructed (red arrows). B–D, Coronal dynamic subtracted postcontrast T1-weighted MR images reveal the transit of contrast from the aorta and cortex, to the medullary renalparenchyma, and into the collecting system, including delineation of the normal ureters and bladder,which is normal in the right kidney and upper pole of the left kidney but incomplete and delayed ofthe abnormal left lower moiety.
effect. Delayed imaging can beobtained to try to demonstratecontrast in the ureter and/orbladder.72
fMRU also has some ancillarydisadvantages, including the need for
sedation or anesthesia foryounger children, cost andavailability of an MR scan, and thepotential adverse events related togadolinium contrast agents.Nephrogenic systemic fibrosis (NSF)has been described with the use of an
older generation of gadolinium-based contrast agents in patientswith severe renal failure, whichlimits its use in patients withadvanced CKD. However, therisk of NSF is thought to belower with newer macrocyclic
FIGURE 13Summary of renal imaging modalities, indications, ionizing radiation risk, nephrotoxic effect, and estimated cost associated. a S/H/UC refers to the needof sedation, IV hydration, and a urinary catheter (UC) for the completion of the study. In general, sedation for any of these imaging tests is only needed inpatients .6 months and ,5 years of age. b Not able to visualize dilated ureter all the time. c Risk of NSF in patients with abnormal renal function isthought to be lower with a newer generation of macrocyclic gadolinium-based contrast agents (eg, gadobutrol, gadoteridol, and gadoterate).d Splitfunction. DMSA, dimercaptosuccinic acid; GU, genitourinary; MCDK, multycystic dysplastic kidney; N/A, not applicable.
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gadolinium-based agents (eg,gadobutrol, gadoteridol, andgadoterate).73 There may also bea risk of gadolinium depositionthroughout the body, butfurther study is required todetermine the clinical significance,if any.74,75
CONCLUSIONS
With new imaging technologies, weattempt to achieve higher imagingresolution, reduce imaging time, andminimize radiation exposure. Theultimate goal is to fullycharacterize CAKUT in youngchildren with a higher degree ofaccuracy while providingnoninvasive prognostic informationin patients at risk for developingCKD.76,77 It is important to continueto develop imaging biomarkers astools to detect progression of renaldisease. Clinicians can use thisreview for reference whennavigating different imagingmodalities (Fig 13) as part of theteam caring for patients withsuspected or known renal disease.To summarize, (1) CEUS is mostpromising in evaluating focal renaldisease, with a comparably favorablesafety profile of the contrast agent;(2) CeVUS has advantages overVCUG, with higher sensitivity for thedetection of clinically significantVUR; (3) fMRU providescomprehensive functionalinformation with improved anatomicinformation when compared withnuclear medicine renograms; and (4)3D-printed models are increasinglyused for training and surgicalplanning in the kidney and urinarysystem. Familiarity with thesetechnologies will allow for easieradoption and wider disseminationof knowledge as, with ongoingresearch efforts, we attempt to shedlight on the natural course of diseaseand guide therapies with safer andmore patient-centered imagingstrategies.
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14 VITERI et al
originally published online January 8, 2020; Pediatrics Hansel Otero
Bernarda Viteri, Juan S. Calle-Toro, Susan Furth, Kassa Darge, Erum A. Hartung andState-of-the-Art Renal Imaging in Children
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