Evaluating the Urothelium With CT Urography: Are We There Yet?

Anne M. Silas, MD, FRCPC

omputed tomography urography (CTU) is a comprehensive cross-sectional CT examination of the upper and lower urinary tract, before and after the intravenous administration of contrast material, including excretory phase imaging.1 The development of multidetector row CT (MDCT) has enabled the rapid acquisition of high-resolution isotropic image data and the generation of high quality 3D image reformations, which are paving the way for multidetector CTU (MDCTU) to become the singular imaging evaluation of the kidneys, renal collecting systems, ureters, and bladder.2 The increased radiation dose that is generated by this examination warrants judicious use of this technique in certain patient populations and clinical scenarios.

Evaluation of the Urinary Tract

Individual unenhanced and multiphasic contrast-enhanced CT examinations have become well established for the detection of calculi and renal parenchymal abnormalities.3,4 Before the advent of MDCT, however, CT was not considered a reliable modality for the detection and staging of urothelial neoplasms.5,6 Even with the development of 4- and 8-slice CT scanners, the lack of isotropic data resulted in missed urothelial lesions.7 Faster data acquisition, improved z-axis resolution, and shorter rotation gantry intervals inherent to 16- and 64MDCT have resulted in improved spatial resolution and the creation of excellent multiplanar reconstruction (MPR) and 3D images, which resemble the traditional IV pyelogram.2 With this advanced technology, several studies have now established the diagnostic usefulness of MDCTU for the evaluation of the urinary tract8-10 (Fig. 1).

ogy revealed that 94% believe CTU is indicated in the evaluation of painless hematuria (Fig. 2). Additional indications include microscopic painless hematuria, suspected transitional cell cancer, transitional cell cancer follow-up, and suspected congenital anomalies.11 The increased radiation dose that is inherent to CTU warrants limiting the application of this study in patients aged 40 years. However, appropriateness of CTU is highly rated by the American College of Radiology for the evaluation of hematuria, excluding those with generalized renal parenchymal disease or young women with hemorrhagic cystitis.13 Additional indications for CTU include unexplained hydronephrosis, smoking, macroscopic compared to microscopic hematuria, exposure to aniline dyes, urinary tract trauma (both iatrogenic and noniatrogenic), and 3D planning for difcult cases of percutaneous nephrolithotomy and surgical reconstruction14,15 (Figs. 3 and 4).

Technique
MDCTU encompasses the use of imaging through the abdomen and pelvis without intravenous contrast, and multiple

Indications
Hematuria is the most common indication for CTU.11,12 A 2005 survey of members of the Society of Urological RadiolDepartment of Radiology, Interventional Radiology and Abdominal Imaging, Dartmouth-Hitchcock Medical Center, Lebanon, NH. Address reprint requests to Anne M. Silas, MD, FRCPC, Department of Radiology, Dartmouth-Hitchcock Medical Center, One Medical Center Dr, Lebanon, NH 03756. E-mail: Anne.M.Silas@Hitchcock.Org

Figure 1 Single thick slab excretory phase maximum intensity projection (MIP) image from a normal MDCTU.

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0037-198X/09/$-see front matter 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.ro.2009.06.001

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Figure 2 Transitional cell carcinoma (TCC) presenting as Gross hematuria and obstruction in an 81-year-old man. Axial unenhanced (A), coronal nephrographic (B), and axial excretory phase (C) images show hyperdense nonenhancing thrombus (white arrows), distending and obstructing the right renal collecting system. Note the incidental nonobstructing calculus. Excretory axial (D) and coronal (E) phase images from a repeat study performed one month following placement of an internal ureteral stent show persistent delay of contrast excretion from the obstructed right collecting system as compared with the left. Heterogeneity within the partially opacied right collecting system and medial central and lower pole urothelial soft tissue thickening (black arrows) is now shown. This was conrmed at biopsy to be TCC.

phases of imaging through the abdomen and pelvis after the administration of intravenous contrast. These multiple sequences are timed to optimize visualization of renal parenchymal and urinary tract structures. Noncontrast imaging through the abdomen and pelvis is used for the detection of urinary tract calculi and calcications. Arterial phase imaging, typically 20-25 seconds after contrast injection, was used to evaluate vascular anomalies and renal arterial anatomy in earlier CTU protocols, although its use in recent protocols has waned as renal masses are best demonstrated in the nephrographic phase.2 The nephrographic phase is imaged approximately 100 seconds after contrast administration. Finally, the urothelium is best imaged in the excretory phase, typically a delay of several minutes after IV contrast administration, which is subject to peristalsis. Image and diagnostic quality of excretory phase evaluation is, therefore, dependent on both distention and

opacication of the collecting system, ureters, and bladder1 (Fig. 5). Although originally, these 4 imaging phases were used as part of the CTU examination, typically only 2-3 phases are used in current examination protocols to limit patient radiation exposure. To reduce the number of scans of the abdomen and pelvis and, therefore, reduce the overall radiation dose of the study, as well as the number of images generated, the nephrographic and excretory phases may be combined. This split bolus technique is characterized by an initial administration of the contrast and after delay, the administration of the remainder of the bolus before imaging the abdomen and pelvis. Imaging then takes advantage of excretion of the initial contrast bolus as well as nephrographic enhancement of the renal parenchyma.16 It remains somewhat controversial whether the split bolus technique yields similar sensitivity and specicity to separated nephrographic and excretory phases.1,17

246 Distention of the renal collecting systems and ureters remains the greatest limitation of this examination, and multiple techniques have been described to try optimizing this. The application of abdominal compression during CTU has not been shown to make any signicant difference in opacication of the renal calices and pelves, nor of the upper

A.M. Silas

Figure 3 Bilateral collecting system rupture in a 56-year-old man presenting with 2 days of hematuria following blunt trauma. Axial unenhanced (A) and nephrographic (B) phase images show bilateral perinephric uid, delayed left nephrogram and unenhancing hyperdense thrombus distending and obstructing the left collecting system (white arrows). Axial excretory phase images (C, D) show retroperitoneal extravasation of opacied urine from bilateral collecting system rupture (black arrows).

Figure 4 A 67-year-old woman with hematuria in the setting of dual large calculi-containing bladder diverticula and chronic bladder infection. Foley catheter in bladder and pigtail catheter within supravesical collection. CTU ordered for planning of surgical reconstruction and identication of stulae. Axial excretory (A) image in wide window setting shows the distal left ureter (white arrowhead) passing into a calculus-containing bladder diverticulum (white star) and stula from diverticulum to bladder (white arrow). Note multiple lling defects consistent with calculi and debris within the thickened bladder. 3D MPR (B, C) demonstrate the position of the distal left ureter (white arrowhead) and diverticular stula to the bladder (white arrow). (Color version of gure is available online.)

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Figure 5 Multiple imaging phases of CTU. Unenhanced (A), arterial (B), nephrographic (C), and excretory (D) phase axial images from a normal CT urogram. Note that renal contrast enhancement is cortical in the arterial phase (B) although distributes into the medulla at nephrographic phase (C). Excretory phase (D) shows contrast opacifying the collecting systems.

and mid ureters when comparing CTU and IV urography (IVU).18 The distention of the distal ureters remains problematic. Although McNicholas et al18 found that scanning the patient in the prone position may improve visualization of the distal ureters, this may not be feasible in practice when attempting to image proximal portions of the upper tracts at the same sitting. McTavish et al,19 however, showed improved opacication of distal ureters after IV saline infusion, with the patient in the supine position. Caoili et al20 compared the use of abdominal compression, the administration of IV saline bolus, and extended excretory phase delay periods. These investigators found that distention of the intrarenal collecting systems and proximal and mid ureters was greater when compression was applied, when a saline bolus was given, and when the excretory delay was increased from 300 seconds to 450 seconds after contrast uric injection. Furthermore, C et al21 demonstrated that imaging in the excretory phase 1 hour after the ingestion of 1000 mL of water, as opposed to imaging at 20 minutes,

resulted in improved distention of the urinary tract. They postulated that prolonged hydration-to-imaging interval promotes diuresis compounded with the obstructing effect of the distended urinary bladder, resulting in improved visualization of the urinary tract, including the distal ureters. Additional maneuvers, such as log rolling, have not shown any difference in ureteral opacication.22 Finally, the intravenous administration of furosemide has been described as an effective method of collecting system distention. The administration of 10 mg IV furosemide 3-5 minutes before contrast injection has been shown to improve pelvicaliceal detail and ureteric opacication at CTU, resulting in less heterogeneity in the collecting system than the administration of IV saline alone.23-25 Axial images acquired with thin beam collimation have resulted in improved three-dimensional (3D) datasets that have enabled high quality postprocessing 3D reformations. This volumetric information may ultimately replace conventional urography as long as viewing and evaluation is per-

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Figure 6 Multifocal TCC within proximal collecting system and ureter in a 79-year-old man presenting with macroscopic hematuria; utility of wide window settings and MPR images. Axial soft tissue excretory phase images at two levels (A, B) through the right kidney show multiple lling defects in the central collecting system and proximal ureter (white arrows). Axial images at the same level as image B in thin section (C) and wide window settings (D) illustrate enhanced detail of disease burden and mucosal abnormalities. Wide window coronal (E, F) and MIP (G) excretory phase images demonstrate these multifocal lesions (white arrows).

Evaluating the urothelium with CT urography

249 formed with thin-section images using wide windows (Fig. 6). Reviewing thin axial section images with MPR scan may also aid in the detection of bladder tumors26 (Fig. 7). Additional techniques, such as virtual CT endoscopy, have been described for urothelial evaluation.27

Detection
CT has become well established as a diagnostic modality for the detection of renal calculi and renal parenchymal abnormalities.28,29 Combining these noncontrast and multiphasic contrast-enhanced examinations with excretory phase imag-

Figure 7 Multifocal TCC in a 72-year-old woman presenting with gross hematuria. Excretory axial (A) and coronal (B) phase images show subtle inltrative left interpolar renal mass (open star) with calyceal invasion (white arrow) and blunting as well as urothelial thickening (white arrows) in the central renal pelvis. Note rigid straightened appearance of the left ureterovesical junction (UVJ) (white arrows). Note incidental upper pole renal cyst (open triangle). Coronal MIP image in wide window settings (C) show calyceal invasion (white arrow) and additional focus of disease within the proximal left ureter (thick white arrow).

Figure 8 Recurrent TCC presenting as solid renal mass with collecting system invasion in an 80-year-old man status post cystectomy and creation of ileal conduit. Axial (A, B) and coronal (C) excretory phase images show a hypodense inltrative interpolar right renal mass (white star) with collecting system invasion characterized by central collecting system lling defects and calyceal distortion (white arrows).

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Figure 9 Multifocal TCC presenting as macroscopic hematuria in an 82-year-old man. Coronal unenhanced images show multiple lling defects within the dilated right renal collecting system (thin black arrows) and proximal ureter (solid black arrow) (A) and severe circumferential bladder wall thickening (thick black arrow) (B).

ing using MDCT has recently been shown to be an effective imaging modality for the diagnosis of urothelial lesions. As compared to IVU, CTU has better sensitivity (100% vs 60.5%), specicity (97.4% vs 90.9%), and accuracy (98.3% vs 80.9%) in the evaluation of asymptomatic microhematuria.30 Supporting these ndings, in a prospective study, Lang et al9 found that CTU was 91% sensitive and 94% specic for the detection of lesions causing microscopic hematuria. Mueller-Lisse et al31 have reported 94% MDCTU sensitivity for the evaluation of urothelial lesions in patients having a history of previous urothelial malignancy or painless macroscopic hematuria. MDCT can detect wall thickening that may not result in alteration of ureteral caliber and, therefore, may remain undetectable at IVU. MDCTU sensitivity and speci-

Figure 10 Bilateral renal cell carcinoma presenting as gross hematuria in a 72-year-old woman. Unenhanced axial image shows bilateral solid renal masses (white star) (A). Note dystrophic calcication within the larger left renal mass. Nephrographic axial image (B) shows complex partially necrotic bilateral renal masses with complete replacement of the left renal parenchyma. Note the right retroperitoneal lymphadenopathy (white diamonds). Axial (C) excretory phase wide window image shows bilateral calyceal and right ureteric invasion (white arrows). Coronal excretory phase image (D) shows frank tumoral invasion into the central left renal collecting system.

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Figure 11 Multiple examples of polypoid intravesical masses in patients presenting with hematuria. Coronal and axial nephrographic images (A, B) through the pelvis in a 66-year-old woman show left bladder mass in the region of the UVJ (white arrow). Axial images (C, D) through the bladder of a 75-year-old man show multiple polypoid bladder lesions (white arrows). Axial and coronal (E, F) excretory phase images in a 61-year-old man show right UVJ lesion (white arrow).

city will likely increase as these examinations are performed on CT scanners with greater number of detectors, such as 16and 64-MDCT scanners. As compared to conventional radiography, lling defects as small as 0.25 mm were identied in phantom models at 64-MDCT, whereas only 3 of these lesions were missed when scanned in the 16-MDCT system.32

Estimated Radiation Dose

The greater the number of imaging phases used in MDCTU, the greater the overall radiation dose will be. Although over-

all radiation dose may play a lesser role in a patient population with a high suspicion of malignant disease, dose remains a signicant issue, particularly for populations of younger patients or those with benign disease.17 Dose reduction, in the form of lower mAs or kV settings on the basis of patient weight, as well as the use of fewer scans may yield sufcient diagnostic information, particularly when the scan is tailored to the patient age and clinical scenario.14,32,33 Kemper et al34 showed that adequate image softtissue detail in pigs could be maintained with signicantly low mAs settings. Furthermore, lower kV settings can also

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reduce overall radiation dose without affecting contrast-tonoise ratio.35 Newer automated tube current modulation software automatically varies CT radiation dose on the basis of patient body habitus. Constant image noise is preserved while maintaining image quality during the examination. Mean effective CTU dose has decreased since CTU was rst used and has now been reported to be as low as 9-15 mSv.36,37 However, discretion toward the application of this relatively high dose examination is warranted.

Imaging Urothelial Lesions of the Upper and Lower Urinary Tract

Collecting System and Ureters
At CTU, urothelial carcinoma may present as hypodense solitary or multiple soft-tissue masses that may enhance. These masses may be inltrative. Thickening of the wall of the collecting system or ureter has been described.38 Nonneoplastic- and inammatory disorders may mimic neoplastic lesions.39 Reviewing thin section axial images as well as curved-

Figure 12 TCC presenting as macroscopic hematuria in a 74-yearold man. Axial (A, B) excretory images through the bladder show exophytic hypodense left UVJ mass (black arrows) encasing albeit not obstructing the left distal ureter and UVJ. 3D MPR (C) conrms position of this mass (identied in blue) with respect to the ureter. (Color version of gure is available online.)

Figure 13 Radiation cystitis in a 75-year-old man status post treatment for prostate cancer who presented with hematuria. Axial soft tissue (A) and wide window (B) images through the bladder show this to be severely irregular and thick walled (arrows).

Evaluating the urothelium with CT urography

planar and MPR images in a wide window setting is required to maximize detection. Dillman et al40 found that reviewing multiple types of images versus reviewing only a single series when interpreting CTU yielded detection sensitivity for urothelial neoplasm to a maximum of 94% on 16-slice MDCT scanners (Figs. 8-10).

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7. Caoili EM, Cohan RH, Inampudi P, et al: MDCT urography of upper tract urothelial neoplasm. AJR Am J Roentgenol 184:1873-1881, 2005 8. Caoili EM, Cohan RH, Korobkin M, et al: Urinary tract abnormalities: initial experience with multi-detector row CT urography. Radiology 222:353-360, 2002 9. Lang EK, Thomas R, Davis R, et al: Multiphasic helical computerized tomography for the assessment of microscopic hematuria: a prospective study. J Urol 171:237-243, 2004 10. Sadow CA, Silverman SG, OLeary MP, et al: Bladder cancer detection with CT urography in an Academic Medical Center. Radiology 249: 195-202, 2008 11. Townsend BA, Silverman SG, Mortele KJ, et al: Current use of computed tomographic urography: survey of the society of uroradiology. J Comput Assist Tomogr 33:96-100, 2009 12. Joffe SA, Servaes S, Okon S, et al: Mutli-detector row CT urography in the evaluation of hematuria. Radiographics 23:1441-1455, 2003 13. Choyke PL, Bluth EI, Bush WH Jr, et al: Radiologic evaluation of hematuria. American College of Radiology. ACR Appropriateness Criteria, 2005. Available at: http://acsearch.acr.org/ProceduresList.aspx?tid68824& vid3070727. Accessed April 24, 2009 14. Nolte-Ernsting C, Cowan N: Understanding multislice CT urography techniques: many roads lead to Rome. Eur Radiol 16:2670-2686, 2006 15. Patel U, Walkden RM, Ghani R, et al: Three-dimensional CT pyelography for planning of percutaneous nephrostolithotomy: accuracy of stone measurement, stone depiction and pelvicalyceal reconstruction. Eur Radiol 19:1280-1288, 2009 16. Chow LC, Kwan SW, Olcott EW, et al: Split-bolus MDCT urography with synchronous nephrogenic and excretory phase enhancement. AJR Am J Roentgenol 189:314-322, 2007 17. Van Der Molen AJ, Cowan NC, Mueller-Lisse UG, et al: CT urography: denition, indications and techniques. A guideline for clinical practice. Eur Radiol 18:4-17, 2008 18. McNicholas MM, Raptopoulos VD, Schwartz RK, et al: Excretory phase CT urography for opacication of the urinary collecting system. AJR Am J Roentgenol 170:1261-1267, 1998 19. McTavish JD, Jinzaki M, Zou KH, et al: Multi detector row CT urography: Comparison of strategies for depicting the normal urinary collecting system. Radiology 225:783-790, 2002 20. Caoili EM, Inampudi P, Cohan RH, et al: Optimization of multi-detector row CT urography: effect of compression, saline administration, and prolongation of acquisition delay. Radiology 235:116-123, 2005 uric 21. C J, Vukelic -Markovic M, Maruic P, et al: Inuence of bladder distension on opacication of urinary collecting system during CT urography. Eur Radiol 18:1065-1070, 2008 22. Kim S, Wang LL, Heiken JP, et al: Opacication of urinary bladder and ureter at CT urography: effect of a log-rolling procedure and postvoiding residual bladder urine volume. Radiology 247:747-753, 2008 23. Silverman SG, Akbar SA, Mortele KJ, et al: Multi-detector row CT urography of normal urinary collecting system: furosemide versus saline as adjunct to contrast medium. Radiology 240:749-755, 2006 24. Nolte-Ernsting CC, Wildberger JE, Borchers H, et al: Multi-slice CT urography after diuretic injection: initial results. Rofo 173:176-180, 2001 25. Sanyal R, Deshmukh A, Singh Sheorain V, et al: CT urography: a comparison of strategies for upper urinary tract opacication. Eur Radiol 17:1262-1266, 2007 26. Jinzaki M, Tanimoto A, Shinmoto H, et al: Detection of bladder tumors with dynamic contrast-enhanced MDCT. AJR Am J Roentgenol 188: 913-918, 2007 27. Battista G, Sassi C, Schiavina R, et al: Computerized tomography virtual endoscopy in evaluation of upper urinary tract tumors: initial experience. Abdom Imaging 34:107-112, 2009 28. Miller OF, Rineer SK, Reichard SR, et al: Prospective comparison of unenhanced spiral computed tomography and intravenous urogram in the evaluation of acute ank pain. Urology 52:982-987, 1998 29. Lang EK, Macchia RJ, Thomas R, et al: Improved detection of renal pathologic features on multiphasic helical CT compared with IVU in patient presenting with microscopic hematuria. Urology 61:528-532, 2003

Bladder
MDCTU for the detection of bladder malignancy remains controversial. Cystoscopy has long been considered the gold standard for the detection and diagnosis of bladder lesions.12 These lesions can present as at tumors that have gone undetected at CTU performed with earlier generation scanners. Sadow et al10 found that the overall sensitivity of CTU for the detection of bladder cancer was less than that of cystoscopy (95.3% vs 78.5%). They also showed that the negative predictive value of CTU was less than that of cystoscopy (95.3% vs 98.9%), although the sensitivity of CTU was greater in the setting of gross hematuria. Turney et al,41 however, compared MDCTU with exible cystoscopy for the detection of bladder lesions in patients aged 40 years presenting with macroscopic hematuria on an 8-slice scanner, and found that CT sensitivity and specicity were 93% and 99%, respectively, whereas positive and negative predictive values were 98% and 97%, respectively (Figs. 11-13).

Conclusion
MDCTU has become a highly sensitive and specic comprehensive imaging modality for the urothelial system and may be a suitable rst-line screening examination for patients aged 40 years with macroscopic hematuria. Distention of the collecting systems and ureters is a persistent limitation of the study, and multiple maneuvers may be used to maximize opacication of these organs. Given the increased radiation dose that accompanies this examination as compared with conventional imaging modalities, judicious use of multiple phases and tailoring of the study to the clinical condition being evaluated is recommended.

References
1. Silverman SG, Leyendecker JR, Amis ES Jr: What is the current role of CT urography and MR urography in the evaluation of the urinary tract? Radiology 250:309-323, 2009 2. Sheth S, Fishman EK: Multi-detector row CT of the kidneys and urinary tract: techniques and applications in the diagnosis of benign diseases. Radiographics 24:e20, 2004 (published online as 10.1148/rg.e20) 3. Wang JH, Shen SH, Huang SS, et al: Prospective comparison of unenhanced spiral computed tomography and intravenous urography in the evaluation of acute renal colic. J Chin Med Assoc 71:30-36, 2008 4. Ulahannan D, Blakeley CJ, Jeyadevan N, et al: Benets of CT urography in patients presenting to the emergency department with suspected ureteric colic. Emerg Med J 25:569-571, 2008 5. Pollack HM, Arger PH, Banner MP, et al: Computed tomography of renal pelvic lling defects. Radiology 138:645-651, 1981 6. McCoy JG, Honda H, Reznicek M, et al: Computerized tomography for detection and staging of localized and pathologically dened upper tract urothelial tumors. J Urol 146:1500-1503, 1991

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30. Gray Sears CL, Ward JF, Sears ST, et al: Prospective comparison of computerized tomography and excretory urography in the initial evaluation of asymptomatic microhematuria. J Urol 168:2457-2460, 2002 31. Mueller-Lisse UG, Mueller-Lisse UL, Hinterberger J, et al: Multidetector-row computed tomography (MDCT) in patients with a history of previous urothelial cancer or painless macroscopic haematuria. Eur Radiol 17:2794-2803, 2007 32. Vrtiska TJ, Hartman RP, Koer JM, et al: Spatial resolution and radiation dose of a 64-MDCT scanner compared with published CT urography protocols. AJR Am J Roentgenol 192:941-948, 2009 33. Stacul F, Rossi A, Cova MA: CT urography: the end of IVU? Radiol Med 113:658-669, 2008 34. Kemper J, Regier M, Bansmann PM, et al: Multidetector CT urography: experimental analysis of radiation dose reduction in an animal model. Eur Radiol 17:2318-2324, 2007 35. Coppenrath E, Meindl T, Herzog P, et al: Dose reduction in multidetector CT of the urinary tract. Studies in a phantom model. Eur Radiol 16:1982-1989, 2006

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36. Nawfel RD, Judy PF, Schleipman AR, et al: Patient radiation dose at CT urography and conventional urography. Radiology 232:126-132, 2004 37. Dahlman P, Jangland L, Segelsjo M, et al: Optimization of computed tomography urography protocol, 1997 to 2008: effects on radiation dose. Acta Radiol 23:1-9, 2009 38. Kawamoto S, Horton KM, Fishman EK: Transitional cell neoplasm of the upper urinary tract: evaluation with MDCT. AJR Am J Roentgenol 191:416-422, 2008 39. Wang J, Wang H, Tang G, et al: Transitional cell carcinoma of upper urinary tract vs benign lesions: distinctive MSCT features. Abdom Imaging 34:94-106, 2009 40. Dillman JR, Caoili EM, Cohan RH, et al: Detection of upper tract urothelial neoplasms: sensitivity of axial, coronal reformatted, and curved-planar reformatted image-types utilizing 16-row multi-detector CT urography. Abdom Imaging 33:707-716, 2008 41. Turney BW, Willatt JMG, Nixon D, et al: Computed tomography urography for diagnosing bladder cancer. BJU Int 98:345-348, 2006