Genitourinary Imaging Original Research

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1 Genitourinary Imaging Original Research Patel et al. MDCT Urography With High-Volume Low-Concentration Contrast Agent Genitourinary Imaging Original Research Sohil H. Patel 1 James S. Babb 1 Nicole Hindman 1 Shigeki Arizono 2 Morton A. Bosniak 1 Alec J. Megibow 1 Patel SH, Babb JS, Hindman N, Arizono S, Bosniak MA, Megibow AJ Keywords: MDCT urography DOI: /AJR Received August 24, 2011; accepted after revision October 6, Department of Radiology, NYU-Langone Medical Center, 550 1st Ave, New York, NY Address correspondence to A. J. Megibow (alec.megibow@nyumc.org). 2 Department of Radiology, Kobe City Medical Center General Hospital, Chuo-ku Kobe, Japan. AJR 2012; 199: X/12/ American Roentgen Ray Society MDCT Urography With High- Volume Low-Concentration IV Contrast Material, Peroral Hydration, IV Furosemide, and IV Saline: Qualitative and Quantitative Assessment in 100 Consecutive Patients OBJECTIVE. The purpose of this study is to qualitatively and quantitatively assess MDCT urography performed with a high volume of low-concentration (240 mg I/mL) IV contrast agent supplemented with peroral hydration, IV furosemide, and IV saline. MATERIALS AND METHODS. This retrospective evaluation of 100 consecutive normal MDCT urograms was performed for clinical indication of hematuria; patients (76 men and 24 women) were years old (mean [± SD] age, 60 ± 15 years). Three radiologists evaluated the degree of opacification across six urinary tract segments (for a total of 1200 measurements per radiologist) on a 4-point scale (0 3). One radiologist measured the maximum short-axis diameter of the proximal, mid, and distal ureters in each patient. Mean opacification scores were calculated for each segment. Radiologist agreement was assessed by kappa coefficient and Spearman rank correlation. Ureteral diameter was correlated to degree of opacification using the Jonckheere-Terpstra trend test. A comparison with published studies using similar scoring methods was undertaken. RESULTS. Of 1200 measured ureteral segments, a total of 24 among the three radiologists were reported as nonopacified. The mean opacification scores ranged from 2.63 ± 0.8 to 3.00 ± 0.8. Calculated kappa coefficients are indicative of substantial agreement (> 0.61). The mean maximal ureteral diameters were 5.44 ± 1.10, 6.32 ± 1.54, and 5.32 ± 1.55 mm for the proximal, mid, and distal ureters, respectively. For all three radiologists, the mean opacification scores increased as distention increased. The Spearman correlation and corresponding p value (p < 0.001) for the association between the distention with the opacification scores show significant correlation. The opacification scores and ureteral distention exceeded published results. CONCLUSION. An MDCT urography technique using high-volume low-concentration IV contrast, oral and IV hydration, and IV diuretic reliably optimizes urinary tract opacification and distention. A positive correlation was found between ureteral distention and opacification. C ross-sectional urography, with either MDCT or MRI, has become the imaging procedure of choice in the workup for patients with hematuria. MDCT urography is more widely used than contrast-enhanced MR urography because of its increased sensitivity to urinary calculi, superior spatial resolution, which allows depiction of small urothelial tumors, and more reliable high-quality examinations [1]. MDCT urography is rated 9 of 9 on the American College of Radiology appropriateness criteria scale [2] for patients with hematuria and has shown excellent clinical efficacy in diagnosing the most serious causes of hematuria [3 5], particularly compared with traditional radiologic techniques [6, 7]. However, there is a wide variety of MDCT urography protocols in clinical practice [8]. The particular methods used to improve urinary tract contrast opacification include peroral hydration, IV hydration, IV furosemide, prone positioning, compression devices, and delayed urographic phase scanning [1]. Split-contrast bolus delivery methods have been adopted by some in an attempt to reduce radiation dosage. At our institution, a modified three-phase protocol is used, supplemented by peroral hydration, IV furosemide, IV saline, and a high volume (200 ml) of low-iodine-concentration (240 mg I/mL) contrast agent. Therefore, the purpose of our study was to quantitatively evaluate the urinary tract opacification and distention achieved with our MDCT urography protocol in 100 consecutive outpatients with normal MDCT urograms. Review of and comparison with prior published studies was subsequently undertaken. AJR:199, July

2 Patel et al. Materials and Methods Institutional review board approval for this HIPAA-compliant retrospective review of patient data was obtained. One hundred consecutive normal MDCT urograms of patients referred between May 1, 2009, and July 16, 2009, for evaluation of hematuria were reviewed. Studies of patients with positive findings related to the clinical diagnosis were excluded. Patients were years old (mean [± SD] age, 60 ± 15 years). There were 76 men and 24 women. All scans were performed on an MDCT scanner (Sensation 64 or AS+, both from Siemens Healthcare). Both systems were operated using a 0.6- mm detector configuration for all acquisitions; in patients younger than 40 years, a 1.2-mm detector configuration was used to lower radiation dose. Specifics of the Imaging Protocol Before entering the scan suite, patients were asked to consume 1000 ml of water over a period of 60 minutes before being placed on the CT table. Although most (> 90%) patients were able to complete this, none drank less than 700 ml. Several minutes before entering the scanning suite, a 20- or 22-gauge IV catheter (BD InSyte Autoguard, Becton Dickinson) was placed and secured with a three-way stopcock (Discofix 3-way stopcock, B. Braun Medical). Immediately before the scan, once the patient was placed on the table, 10 mg of furosemide was administered IV, followed by acquisition of a localizer image of the abdomen and pelvis. Furosemide is not administered to patients with a furosemide allergy or an allergy to sulfonamides. Low blood pressure (i.e., systolic blood pressure < 90 mm Hg) is also a contraindication. Furosemide was not contraindicated in any patient in our study population, and no adverse outcomes occurred in our patient cohort. All acquisitions were obtained using a 0.6-mm detector and reference tube current of 240 ma for automated dose modulation (CareDose 4-D, Siemens Healthcare). Isotropic voxels (0.75 mm) are generated and reconstructed with a 20% overlap. For each acquisition, 4-mm-thick axial images (at 4-mm increments) and 3-mm-thick coronal images (at 3-mm increments) are sent to the PACS workstation. These are supplemented by 0.75-mm thin images that are sent to an offline workstation (Leonardo, Siemens Healthcare) for 3D viewing and creation of both volume-rendered and maximum-intensity-projection images (Fig. 1). For patients younger than 40 years, a 1.2-mm detector was used, generating 1.5-mm isotropic voxels. All other parameters were unchanged. Images were obtained from the xiphoid through the kidneys during the unenhanced phase and over the entire abdomen and pelvis for the nephrographic and urographic phases. All patients were scanned in the supine position. Nephrographic phase images were obtained 80 seconds after the initiation of IV contrast administration. Urographic phase images were obtained 7 minutes after initiation of IV contrast administration. All studies were performed using 200 ml of iopromide (240 mg I/mL; Ultravist 240, Bayer HealthCare) administered at a minimum rate of 2 ml/s. In addition, 100 ml of normal saline was administered IV at 1 ml/s during the interval between the nephrographic and urographic phases. Image Analysis Images were analyzed independently by three radiologists. These radiologists were, respectively, a third-year radiology resident, a third-year abdominal imaging attending physician, and a visiting radiologist who is a first-year attending physician. Reviewers were asked to judge the degree of opacification on a 4-point scale (0 = unopacified; 1 = 1 49% opacified; 2 = 50 99% opacified; and 3 = 100% opacified). Each side was divided into six segments intrarenal collecting system upper pole, renal pelvis, intrarenal collecting system lower pole, proximal ureter (ureteropelvic junction to iliac crest), mid ureter (iliac crest to superior aspect of greater sciatic notch), and distal ureter (superior aspect of greater sciatic notch to ureterovesical A Fig year-old woman. A and B, Volume-rendered MDCT urogram (A) and maximum-intensity-projection image (B) display duplication of left collecting system and ureter. junction) as defined by Silverman et al. [9] and McTavish et al. [10] (Fig. 2). Each radiologist was provided with a reference set of images that defined each of the grades of opacification as previously published. A total of 1200 measurements were recorded by each of the three reviewers. Reviewers were permitted to evaluate all of the urographic image data; however, if there was a question of opacification on 3D volume or maximum-intensity-projection images, they were specifically instructed to make their final judgment from the axial images (Fig. 3). In addition, one radiologist independently recorded the maximal short-axis diameter of the proximal, mid, and distal ureters for each patient. Location of the measurement was based on visual inspection of each segment. Measurements were made using electronic calipers on the 4-mm axial images displayed on the PACS. When possible, calipers were placed in the midportion of the ureteral wall; however, if the ureteral wall was too thin to support this level of precision, outer wall-to-wall measurements were recorded. A single measurement was recorded within each ureteral segment. Care was taken to avoid measuring the ureteral diameters at any level where extrinsic compression by iliac or other vessels could influence ureteral shape. Mean opacification scores for each segment for each radiologist were calculated. Radiologist agreement was assessed by determining kappa and B 112 AJR:199, July 2012

3 MDCT Urography With High-Volume Low-Concentration Contrast Agent Fig year-old man. Volume-rendered MDCT urogram image from urographic phase acquisition illustrates location of urinary segments used in analyses. Numbers are defined as follows: 1 = upper pole intrarenal collecting system, 2 = renal pelvis, 3 = lower pole intrarenal collecting system, 4s = superior margin, proximal ureter, 4i = inferior margin of proximal ureter, 5s = superior margin of mid ureter, 5i = inferior margin of mid ureter, 6s = superior margin of distal ureter, and 6i = inferior margin of distal ureter. As defined on axial imaging, 4s to 4i is ureteropelvic junction to top of iliac crest, 5s to 5i is top iliac crest to greater sciatic notch, and 6s to 6i is greater sciatic notch to ureterovesical junction. Spearman rank coefficients. The mean ureteral diameters recorded for each segment were correlated with mean opacification scores using the Jonckheere-Terpstra trend test. Results Of 1200 measured ureteral segments, a total of 24 among the three radiologists were reported as nonopacified (i.e., opacification score of 0). The opacification scores per segment per radiologist are shown in Table 1. The range is 2.63 ± 0.8 to 3.00 ± 0.8. The radiologists exhibited relatively close agreement in the sense that the mean scores they provided for any segment never differed by more than 0.14 units on the 4-point rating scale. The mean score from any radiologist was never lower than 2.63 relative to a maximum score of 3. Calculated kappa coefficients between radiologist pairs for overall assessment of opacification of the same segments in the same subjects were 0.87 between radiologists 1 and 2, 0.69 between radiologists 1 and 3, and 0.67 between radiologists 2 and 3, indicative of substantial interradiologist agreement (κ > 0.61). Spearman rank correlations to assess the agreement between radiologists in terms of overall opacification for the same segments in the same subjects were 0.86 between radiologists 1 and 2, 0.69 between radiologists 1 and 3, and 0.72 between radiologists 2 and 3. All correlations were highly significant (p < 0.001) except for those involving radiologist 3 and the renal pelvis. The mean maximal ureteral diameter was 5.44 ± 1.10 mm for the proximal ureter, 6.32 ± 1.54 mm for the middle ureter, and 5.32 ± 1.55 mm for the distal ureter. The mean radiologist opacification scores as a function of ureteral distention showed that the mean opacification score increased as measured distention increased (Table 2). The Spearman correlation and corresponding p value for the association between the distention scores provided by radiologist 1 with the opacification scores provided for the same location by each of the three radiologists showed a high degree of correlation (Table 3). For all three radiologists, mean opacification scores increased along with every increasing increment of ureteral diameter. Ureteral opacification was substantially lower when the distention was 4 mm or less than when it exceeded 4 mm. Assessing radiologist concordance as a function of ureteral diameter revealed that agreement between radiologists 1 and 2 was essentially independent of measured distention, whereas radiologist 3 was noticeably less likely to agree with either of the other two radiologists when the measured distention was low, especially when the distention was 4 mm or less (Table 4). Discussion The use of a high volume of diluted IV contrast media for excretory urography was first reported in The excellent excretory urograms achieved with this technique are based on the supposition that the larger volume of fluid promotes hydration and diuresis, leading to improved filling and distention of the urinary tract. The original description of this technique advised administration of 300 ml of an approximately 25% solution [11]. We think that this same principle provides the distention and urinary tract filling to maximize the technical quality of MDCT urography. We administer a lower concentration of IV contrast medium (240 mg I/mL as opposed to traditional 300 mg I/mL solutions) in a high fluid volume (200 ml). By supplementing this increased fluid with 1000 ml of water consumed over the 60 minutes before imaging, 10 mg of IV furosemide immediately before obtaining localizer images, and 100 ml of IV saline, we provide the kidneys an increased fluid load that both distends and fills the urinary tract structures. The larger more diluted contrast agent also Fig year-old man. Axial 4-mm-thick image through mid kidneys was obtained during urographic phase of MDCT urogram. There is no streaking from concentrated iodinated contrast agent opacifying collecting systems. AJR:199, July

4 Patel et al. TABLE 1: Opacification Scores by Segment and Radiologist Segment, Side Radiologist 1 Radiologist 2 Radiologist 3 Upper intrarenal collecting system Right 2.85 ± ± ± 0.20 Left 2.88 ± ± ± 0.20 Lower intrarenal collecting system Right 2.86 ± ± ± 0.20 Left 2.85 ± ± ± 0.24 Renal pelvis Right 2.96 ± ± ± 0.00 Left 2.97 ± ± ± 0.10 Proximal ureter Right 2.79 ± ± ± 0.33 Left 2.79 ± ± ± 0.42 Middle ureter Right 2.70 ± ± ± 0.45 Left 2.82 ± ± ± 0.41 Distal ureter Right 2.63 ± ± ± 0.68 Left 2.69 ± ± ± 0.57 Note Data are mean ± SD opacification score. Opacification was graded on scale of 0 3, where 0 = segment nonopacified, 1 = 1 49% opacified, 2 = 50 99% opacified, and 3 = 100% opacified. minimizes the streak artifacts generated by the concentrated contrast column in the renal pelvis and ureters [12]. On our urograms, the contrast column has a translucent quality that allows abnormalities to be seen through the opaque material. Our results confirm the concept that superior urograms, based on consistent and reproducible opacification, are the direct result of improved urinary tract distention. The mean opacification scores for any segment for any radiologist were never below 2.63 ± 0.8, with strong interradiologist agreement, as measured by kappa and Spearman rank correlations. Although radiologists 1 and 2 were almost identical in their perceptions, the discrepancies with radiologist 3 can be attributed to radiologist 3 s higher scoring in the renal pelvis. Although the distal ureters consistently displayed the lowest diameters, their mean diameter (5.32 ± 1.55 mm) was only slightly less than those of the proximal (5.44 ± 1.10 mm) or mid ureter (6.32 ± 1.54 mm). Both mean opacification scores and radiologist agreement improved as ureteral distention increased; the greatest fall-off in both radiologist opacification score and concordance occurred when the ureteral diameter was smaller than 4 mm. In the past decade, a number of groups have described the independent efficacy of a variety of techniques to improve MDCT urography. Although peroral hydration [13] and IV furosemide [9, 14] are more definitively associated with improved urinary tract opacification than IV saline administration [10, 15, 16], we choose to use all three methods because they are all safe, low cost, and conveniently administered. Although the 7-minute delay used for urographic phase acquisition was determined largely on the basis of institutional experience and workflow efficiency, Kemper et al. [17] experimentally validated precisely 7 minutes as the median urographic phase delay required for maximal distal ureteral opacification. In addition, the 60-minute delay we apply between initiating peroral hydration and image acquisition is supported by the work of Ćurić et al. [18], who showed improved ureteral opacification in patients who ingested 1000 ml of water 60 minutes before scanning, compared with those who ingested water 20 minutes before scanning. We do not use compression devices or longer urographic phase delays, because their application has not proven sufficiently beneficial for their cost and time [19, 20]. A review of the literature provided several studies in which the effects of each of our technical interventions could be assessed independently. For instance, several groups reported urinary tract opacification or distention supplemented with IV saline alone. McTavish et al. [10] used the same opacification scoring system as in the present study and reported a mean distal ureteral segment score of 2.2. Huang et al. [21] reported that approximately 50% of distal ureters were completely opacified (vs > 80% with our protocol). Caoili et al. [15] reported overall mean ureteral diameter less than 4 mm and a greater number of nonopacified urinary tract segments compared with our data, although their scoring system was slightly different than in the present study. In terms of peroral hydration, Szolar et al. [13] reported urinary tract opacification in patients undergoing CT urography supplemented with peroral hydration (at varying doses of IV contrast agent), using a scoring system slightly modified compared with ours. For instance, in their study, a score of 3 equaled % opacified segment. Despite differences in scoring, they reported opacification scores uniformly lower than those in our protocol. It should be recognized, however, that their report provided important data supporting the effect of peroral hydration as well as higher contrast agent volumes in ensuring adequate urinary tract opacification. Kawamoto et al. [22] likewise reported urinary tract opacification in CT urography supplemented with peroral hydration alone. They reported lower opacification scores compared with our data, most significantly within the intrarenal collecting system and distal ureteral segment. TABLE 2: Ureteral Opacification Scores as a Function of Ureteral Distention Distention (mm) Radiologist 1 Radiologist 2 Radiologist ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 0.24 Note Data are mean ± SD opacification score. 114 AJR:199, July 2012

5 MDCT Urography With High-Volume Low-Concentration Contrast Agent TABLE 3: Spearman Correlation (r) and Corresponding p Value for Association Between Ureteral Distention Scores Provided by Radiologist 1, With Opacification Scores at the Same Location by Each Radiologist Radiologist 1 Radiologist 2 Radiologist 3 Location Side r p r p r p Proximal Both 0.29 < < Middle Both 0.37 < < < Distal Both 0.26 < < < Kemper et al. [17] reported the effect of IV furosemide alone. In their protocol, 0.1 mg/kg IV furosemide was administered 90 seconds before contrast agent administration. Test slices at the level of the iliac crest were acquired to ensure distal ureteral opacification before urographic phase imaging. Despite test slice acquisition, they reported that 7.8% of distal ureters were unopacified (compared with 3.5% in our study). Using a scoring system identical to ours, Silverman et al. [9] reported opacification scores and ureteral diameters in MDCT urography supplemented with peroral hydration as well as varying combinations of IV furosemide and IV hydration. The main differences between their protocol and ours were their use of 100 ml of iopromide (300 mg I/mL); 250 ml of saline, as opposed to 100 ml in the present study; 900 ml of peroral hydration, which was almost equivalent to 1000 ml in the present study; and a 15-minute excretory phase delay, compared with 7 minutes in the present study. Of note, they did not report the time interval from peroral hydration to scanning. Furthermore, they reported significant interobserver variability for opacification scoring, and their opacification scores are predominantly reported graphically, making direct comparison difficult. Extrapolating from the numeric data they do provide, their opacification scores were overall slightly lower compared with our data. Our distention scores were superior at every segment. Graphically, they indicated mean maximum proximal ureteral diameters less than 5 mm, compared with 5.40 mm on the right and 5.48 mm on the left as measured in the present study. Their reported mean maximal mid ureteral diameters were 6.08 mm on the right and 5.96 mm on the left, compared with 6.47 and 6.17 mm, respectively, in our study. Their reported maximal distal ureteral diameters were 4.53 mm on the right and 4.61 mm on the left, compared with 5.17 and 5.47 mm, respectively, in our study. Although the statistical significance of these differences is not tested, for each anatomic segment compared, our study generated higher values. Current interest in split-bolus MDCT urography is directly related to the possibility of reducing radiation dose by limiting the number of acquisitions. This technique has been shown to be able to detect renal and urinary tract causes for hematuria in a significant number of patients [23, 24]. However, experimental studies examining the quality of the urograms on the basis of ureteral opacification and distention show diminished-quality urograms compared with standard single-bolus techniques [25]. Wang et al. [26] reported urinary tract opacification using a split-bolus protocol supplemented with peroral hydration and varied patient positioning (prone vs supine). Opacification scoring was similar with our system (0 3 point scale), though at baseline their system attributed slightly higher scores for given levels of opacification. They reported uniformly lower opacification scores; in particular, their average distal ureteral score was less than 2 in both supine and prone positioning. Kekelidze et al. [27] recently reported opacification scores and ureteral diameters using a triple-contrast bolus and single contrast-enhanced acquisition. Twenty-one percent of their distal ureters were unopacified (vs 3.5% with our technique). Our reported mean ureteral diameters were 28 43% greater at every segment compared with theirs. Sanyal et al. [14] reported urinary tract opacification using a split-bolus technique. Compared with our data, they reported lower opacification scores in all but one of their patient groups. However, their reading method makes direct comparison with our data somewhat problematic. Although it is not the purpose of this study, it is worth noting that our nephrographic phase is performed at 80 seconds after contrast agent administration to ensure that contrast agent has not been excreted into the urinary tract. This allows the detection of distal ureteral and bladder calculi, allowing us to limit the unenhanced phase to the kidneys and to minimize radiation to the pelvis to two passes. Furthermore, this slightly early nephrographic phase allows us to inspect the urothelium for small enhancing foci on the background of a water attenuation lumen. Park et al. [28] have found excellent accuracy of nephrographic phase imaging for the detection of bladder cancers. In our experience, the combined nephrographic and urographic phases increase confidence in detection of small urothelial lesions (Fig. 4). As already discussed, standard multiphase MDCT urography does expose the patient to more radiation than with the split-bolus technique. To minimize radiation dose, we limit our acquisition through the pelvis to two passes. We routinely use dose-modulation software and a reference tube current of 240 ma. This results in a volume CT dose index of mgy, depending on the size of the patient. These doses are well within an acceptable dose range and provide an optimal examination for a clinically indicated examination. We have further reduced the dose (subsequent to our technique used to collect the reported data) by decreasing the reference tube current to 180 ma for the unenhanced phase. We also use a wider detector configuration on all phases of acquisition for individuals younger than 40 years, further decreasing radiation exposure in this patient subset. Because we obtain our nephrographic phase images at a slightly earlier time (for the aforementioned reasons), the kidneys sometimes show corticomedullary differentiation. TABLE 4: Percentage of Times Radiologists Had Concordant Assessments of Ureteral Opacification as a Function of Ureteral Distention Distention (mm) Radiologists 1 and 2 Radiologists 1 and 3 Radiologists 2 and AJR:199, July

6 Patel et al. Imaging at this time has been shown to decrease the ability to perceive a small renal mass [29]. The radiologist must examine both nephrographic and urographic phase images in parallel, with the latter phase often highlighting parenchymal defects that can be further correlated with the unenhanced and nephrographic phase images (Fig. 4). There are limitations to our study. We chose to examine our current technique (in clinical use since 2006), benchmarking our results against those reported in the literature, rather than prospectively testing the individual components of our protocol. In addition, we chose only patients with normal examinations. A formal meta-analysis of the CT urography literature is problematic given the variety of methods used to score urinary tract opacification and distention; however, no prior study to our knowledge has shown a CT urography protocol that produces superior combined urinary tract opacification and distention compared with our protocol. In conclusion, MDCT urography using a high volume of low-concentration IV contrast agent, preprocedural peroral hydration, IV furosemide administration, and IV saline infusion reproducibly creates urograms characterized by high levels of urinary tract opacification and distention. We have also shown a high degree of correlation between ureteral opacification and distention. A Fig year-old man who had undergone cystectomy and ileal conduit for transitional cell carcinoma of urinary bladder (and therefore was not part of study cohort). A, Axial image (4 mm thick) obtained during nephrographic phase of MDCT urogram illustrates value of multiphasic acquisitions in detecting small urothelial cancers. Study was performed for urothelial surveillance. Note hyperdense nodule (arrow) along superior aspect of left renal pelvis. Visualization is accentuated by water density of nonopacified urine. Note that kidney displays corticomedullary differentiation, which may make detection of small parenchymal masses difficult. B, Urographic phase image confirms soft-tissue mass (arrow). Renal parenchyma is uniformly enhanced, facilitating detection of small masses that might be obscured during corticomedullary phase. As in Figure 3, there is no streaking from calyces or renal pelvis. 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 2009; 250: Ramchandani P, Kisler T, Francis IR, et al. 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