Dual-Energy CT for Quantification of Urinary Stone Composition in Mixed Stones: A Phantom Study

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1 Genitourinary Imaging Original Research Leng et al. Dual-Energy CT of Urinary Stones Genitourinary Imaging Original Research Shuai Leng 1 Alice Huang 1 Juan Montoya Cardona 1 Xinhui Duan 1,2 James C. Williams 3 Cynthia H. McCollough 1 Leng S, Huang A, Montoya Cardona J, Duan X, Williams JC, McCollough CH Keywords: dual-energy CT, mixed stones, stone composition, urinary stones DOI:1.2214/AJR Received October 2, 215; accepted after revision February 18, 216. C. H. McCollough receives research funding from Siemens Healthcare. Supported by grant DK1227 from the National Institute of Diabetes and Digestive and Kidney Diseases and training grant R25 DK1145 for Mayo Clinic summer undergraduate research in nephrology and urology. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 1 Department of Radiology, Mayo Clinic, 2 First St SW, Rochester, MN Address correspondence to S. Leng (leng.shuai@mayo.edu). 2 Present address: Department of Radiology, University of Texas Southwestern, Dallas, TX. 3 Department of Anatomy and Cell Biology, Indiana University, Indianapolis, IN. AJR 216; 27: X/16/ American Roentgen Ray Society Dual-Energy CT for Quantification of Urinary Stone Composition in Mixed Stones: A Phantom Study OBJECTIVE. The purpose of this study was to assess the feasibility of using dual-energy CT to accurately quantify uric acid and non uric acid components in urinary stones of mixed composition. MATERIALS AND METHODS. A total of 24 urinary stones were analyzed with micro CT to serve as the reference standard for uric acid and non uric acid composition. These stones were placed in water phantoms to simulate body attenuation of slim to obese adults and scanned with a third-generation dual-source CT scanner by use of dual-energy modes adaptively selected on the basis of phantom size. CT number ratio, which is distinct for different materials, was calculated for each pixel of the stones. Each pixel was then classified as uric acid and non uric acid by comparison of the CT number ratio with preset thresholds ranging from 1.1 to 1.7. Minimal, maximal, and root-mean-square errors were calculated by comparing composition with the reference standard, and the threshold with the minimal root-mean-square error was determined. A paired t test was performed to compare the stone composition determined with dual-energy CT with the reference standard obtained with micro CT. RESULTS. The optimal CT number ratio threshold ranged from 1.27 to 1.55, dependent on phantom size. The root-mean-square error ranged from 9.6% to 12.87% across all phantom sizes. Minimal absolute error ranged from.4% to 1.24% and maximal absolute error from 22.5% to 35.46%. Dual-energy CT and the reference micro CT did not differ significantly on uric acid and non uric acid composition (paired t test, p =.2.96). CONCLUSION. Accurate quantification of uric acid and non uric acid composition in mixed stones is possible with dual-energy CT. I n addition to aiding in detection of stone location and quantification of stone size, dual-energy CT (DECT) is being used to differentiate the chemical composition of urinary stones to assist with treatment [1 1]. Several techniques have been used to perform dual-energy examinations, including dual-source CT, fast voltage switching, use of dual-layer detectors, and acquisition of two consecutive scans with different tube potentials [1, 6, 8, 11, 12]. The most successful application of DECT is to differentiate uric acid (UA) from non-ua stones on the basis of the substantial difference in the effective atomic number of these stones. This information is critical because UA stones can be treated with urinary alkalization rather than a surgical procedure. Accurate differentiation of UA from non-ua stones has been evaluated in in vitro phantom studies and in vivo patient studies [1 4, 13]. Researchers have also investigated methods to further differentiate among the types of non-ua stones [5, 11, 14 16]. Most studies in the literature have focused on pure stones, that is, those composed of a single material. Use of such stone samples simplifies data analysis and has led to the finding that DECT can be used to differentiate types of stones. However, most urinary stones are mixed, containing two or more materials [17, 18]. Therefore, it is essential to identify and quantify individual components inside each stone to ensure proper management. Several studies of the use of DECT to differentiate stone materials [2 5] have included a few mixed stones in addition to pure stones. However, none of these studies quantified each component within a mixed stone. To determine whether stone composition can be differentiated and quantified with DECT, a reference standard of stone composition is needed. Several techniques have AJR:27, August

2 Leng et al. been used as standards, such as x-ray diffraction crystallography, infrared spectroscopy, and wet chemical analysis [19]. Infrared spectroscopy is the most widely used method of in vitro stone composition analysis and has been used as the reference standard in most published studies [1, 5, 7, 9, 13, 14, 16, 2]. However, in infrared spectroscopy, only part of the stone is sampled, limiting the ability of the technique to accurately show the composition of mixed stones [21]. Micro CT has been found useful for accurate determination of mixed mineral components without destroying the stone, as infrared spectroscopy does [21 23]. Unlike infrared spectroscopy, micro CT yields 3D images of the whole stone and is therefore well suited for determining the heterogeneity of mixed stones. However, this research technique requires an isolated stone and therefore is not a substitute for clinical techniques such as DECT. Calcium oxalate and UA have dramatically different x-ray attenuation values in micro CT [22, 24], allowing measurement of mineral percentages for each stone by means of gray-scale segmentation of the image stacks [23]. Measurement of mineral percentages in a given stone has been found quite reproducible, the coefficients of variation of the material having the larger fraction averaging 1.9% ±.8% (SD). The combination of microscopic localization of minerals [24] with the dramatically different x-ray attenuations of UA and calcium salts in micro CT [22] allows use of this process as a reference standard for the actual percentage of UA in each stone. The purpose of the current study was to assess the feasibility of using DECT to accurately quantify UA and non-ua components in urinary stones of mixed composition. Materials and Methods Kidney Stone Selection and Micro CT Scans A total of 24 urinary stones with previously acquired micro CT data showing mixed UA and non-ua composition were selected for this study. Stones with diameters of 5 mm and larger were included in the study. No internal review board approval was required, because all stones were obtained without information related to patient identifiers. All of the stones were first scanned with micro CT to determine the chemical composition; the result was used as the reference standard for stone composition. Micro CT scans were obtained by use of a Skyscan 1172 system (Bruker) with a tube potential of 6 kv and a.5-mm aluminum filter at the source. Stones were scanned to obtain image stacks with cubic voxels measuring 6 1 μm. Chemical composition based on micro CT result and corroborated with infrared spectroscopy of cohort stones was used as the true composition of each stone (Fig. 1). All stones were hydrated in distilled water for 24 hours before the DECT experiments to mimic the clinical scenario, in which stones are surrounded by urine. Each stone was placed in an individual water-filled vial, and air bubbles were eliminated from around the stones. All of the vials were then placed into a water phantom (Fig. 2) containing a plastic grid to hold the vials in place. To investigate the effect of patient size on image quality and accuracy of quantification of stone composition, six phantoms with lateral widths of 3, 35, 4, 45, 5, and 55 cm were used to simulate different patient habitus. Each of the 24 stones was scanned in each of the six phantoms, and all data were analyzed for each phantom. To minimize variability in positional configuration, stones remained fixed in the plastic grid (Fig. 2B) when transferred between phantoms and were centered in each phantom. CT Scans and Image Reconstruction Scans were performed on a 192-MDCT (96 detector rows with flying focal spot technique) dualsource scanner (Somatom Force, Siemens Healthcare) according to our clinical dual-energy urinary stone composition protocol. The dual-energy scan modes (tube potential pairs) were selected on the basis of phantom size. A.6-mm tin (Sn) filter was added to the high tube potential (15 kv) to increase spectral separation and consequently material decomposition capability [15, 25 28]. Key scanning parameters, such as tube potential and tube current time product, are summarized in Table 1. These parameters were selected so that the volume CT dose index (CTDI vol ) would be the same for phantoms of the same size, even with use of different tube potential pairs. CTDI vol was 18 mgy for a standard-sized adult (attenuation equivalent to a 33-cm-diameter water phantom), approximately 7 8 kg. Tube current modulation (CARE Dose4D, Siemens Healthcare) was used to adapt the tube current according to phantom size and to optimize dose delivery within the scan plane. This improves consistency of image quality along the z-axis relative to scans performed without tube current modulation [29]. Images were reconstructed with a medium-smooth dual-energy kernel (Qr4) at 1-mm image thickness and.8-mm increment for both low- and high-energy datasets. TABLE 1: Key Scanning and Reconstruction Parameters Used in Dual-Energy CT Examinations Parameter Value Scan type Spiral, dual energy Rotation time (s).5 Collimation (mm) Pitch.6 Tube potential pair at specific phantom size (kv) 3 cm 7/Sn15 35 cm 7/Sn15 4 cm 8/Sn15 45 cm 9/Sn15 5 cm 1/Sn15 55 cm 1/Sn15 Quality reference tube current time product for low- and high-energy tubes (mas) 3 cm 875/ cm 875/219 4 cm 5/25 45 cm 35/219 5 cm 3/15 55 cm 3/15 Tube current modulation On Recon kernel Qr4 Image thickness (mm) 1 Image increment (mm) AJR:27, August 216

3 Dual-Energy CT of Urinary Stones Dual-Energy Processing The reconstructed images were postprocessed with custom urinary stone analysis software programmed in Matlab (version 214, MathWorks). The locations of the stones were automatically detected by the software after loading of the DICOM images. Stones were then segmented by use of a threshold-based method with the threshold adapted to the attenuation of each stone [3]. The CT number ratio, defined as the ratio of the CT number at the low tube potential to the CT number at the high tube potential, was calculated for each pixel of the stone. Each pixel of the stone was classified as UA or non-ua by comparison of the CT number ratio at the pixel to a predetermined CT number ratio threshold. Pixels with a CT number ratio lower than the threshold were classified as UA, and those with a ratio higher than the threshold were classified as non-ua. The percentages of UA and non-ua for each stone were then calculated from the number of UA and non-ua pixels in the whole stone. Statistical Analysis The UA percentage stone composition obtained from the DECT images at a given CT number ratio threshold was compared with that of the reference standard obtained by micro CT. The error for the UA component was calculated for each stone and CT number ratio threshold value. Because the stones contained only UA and non-ua components, the non-ua error was the same in magnitude but opposite sign as the UA error. Therefore, UA error was used in all subsequent data analyses. The root-mean-square error (RMSE) over all stones was calculated as follows: RSME = 1 N (UA DECT UA microct ) 2, N i = 1 where N is the number of stones (24 in this study), UA DECT is the UA percentage determined from DECT images, and UA microct is the UA percentage determined from micro CT, which was used as the reference standard. Because stone composition (UA or non-ua) was determined by comparing the measured CT number ratio values with the CT number ratio threshold used to separate UA from non-ua components, the specific value of the selected CT number ratio threshold affected the RMSE. In this study a series of CT number ratio threshold values, ranging from 1.1 to 1.7 and incremented by.1, were used to determine the optimal threshold for each phantom size and dual-energy scan mode. The range was selected so that it was wide enough to cover all reasonable threshold values. Because the CT number ratio of UA stones is approximately 1., that of non- UA stones is between 1.4 and 2., and the optimal threshold for differentiating UA from non-ua is TABLE 2: Volume and Composition of Each Stone as Measured With Micro CT Stone No. Volume (mm 3 ) Uric Acid Content (%) Non Uric Acid Content (%) Note Stones are presented in order of increasing volume. expected to be between the CT number ratios of UA and non-ua components [15], the thresholds investigated ( ) were considered sufficient to include all reasonable threshold values. RMSE was calculated for each CT number ratio threshold, and the threshold associated with the minimal RMSE was defined as the optimal threshold. This process was repeated for each phantom size and dual-energy scan mode because previous studies showed that the optimal threshold varies with phantom size and tube potentials [15]. The error in UA percentage composition for each stone was then calculated by use of this optimal threshold. Minimal and maximal errors (in absolute values) from all stones were also calculated. For each phantom size, a paired t test was performed to compare the UA stone composition from micro CT and DECT with p <.5 considered statistically significant. Results Stone Volume and Composition From Micro CT The volumes and compositions of each stone (24 total) determined with micro CT are listed in Table 2. Stone volume ranged from 75.3 to mm 3 (mean, 17.2 [SD, 61.9] mm 3 ), which covered the range of stone sizes typically seen in patients. Among these stones, one was pure UA, one was pure non- UA, and the other 22 were mixed stones. In the 22, the proportion of UA ranged from 12% to 93%, and the percentage of non-ua content ranged from 7% to 88%. Stone Composition From Dual-Energy CT Example DECT images of a mixed stone scanned with the 7/Sn15-kV dual-energy mode in a 3-cm phantom are shown in Figures 3A and 3B. The measurements from micro CT indicated that this mixed stone was 49% UA and 51% non-ua. The CT number ratio map is shown in Figure 3C. Composition maps at different CT number ratio thresholds, with UA pixels in red and non- UA pixels in blue, and the corresponding calculated errors of the UA estimation are shown in Figures 3D 3F. For a very low CT AJR:27, August

4 Leng et al. TABLE 3: Measurement Parameters and Results of Comparison of Stone Composition Quantification With Dual-Energy CT and Micro CT Phantom Size (cm) Dual-Energy Mode by Pair (kv) number ratio threshold (e.g., 1.1, as shown in Fig. 3D), more pixels were classified as non-ua, which underestimated the UA components (by 46% for the example shown in Fig. 3D). Conversely, for a very high CT number ratio threshold (e.g., 1.7, as shown in Fig. 3F), more pixels were classified as UA, which overestimated the UA component (by 26% for the example shown in Fig. 3F). A midrange CT number ratio threshold (e.g., 1.55 in Fig. 3E) produced minimal error (6% for the example shown in Fig. 3E). Figure 4 shows two examples of DECT quantification of stone composition. Micro CT images (Figs. 4A and 4B) showed clear mixed stone composition (49% UA, 51% non-ua; 43% UA, 57% non-ua). Mixed DECT images (Figs. 4C and 4D) showed the same outline of the stones as did the micro CT images but with much less detail of the inner structure. The CT number ratio map showed that the UA and non-ua composition determined with DECT (54% UA, 46% non-ua; 53% UA, 47% non-ua) was close to that of the corresponding micro CT results (error, 5% and 1%). For all CT number ratio thresholds at different phantom sizes and dual-energy scan modes, RMSE first decreased as CT number ratio threshold increased from 1.1 and then increased as the ratio approached 1.7 (Fig. 5 and Table 3). The optimal CT number ratio threshold, which corresponded to the minimal RMSE, depended on phantom size and dual-energy scan mode. For example, it was 1.55 for the 3-cm phantom scanned with the 7/Sn15 scan mode and 1.28 for the 55-cm phantom scanned with the 1/Sn15 scan mode. In general, the optimal CT number ratio was higher for DECT scan modes with lower tube potentials (i.e., 7 or 8 kv) for the low-energy beam compared with those with higher tube potentials (i.e., 9 and 1 Optimal CT Number Ratio Threshold Root-Mean-Square Error (%) a kv) for the low-energy beam. This phenomenon occurred because CT number and hence CT number ratio strongly depend on tube potential. For the same urinary stone, the CT number is higher at lower tube potentials. Because the high-energy beam was the same for all DECT scan modes (i.e., 15 kv with Sn filtration), the CT number ratio of each stone was higher for DECT modes with lower tube potential on the low-energy beam. The RMSE ranged from 9.6% to 12.87%. The minimum absolute UA error ranged from.4% to 1.24%, and the maximum absolute UA error ranged from 22.5% to 35.46% (Fig. 6 and Table 3). Both positive and negative errors were observed, indicating that some UA components were estimated as non-ua and vice versa. No clear bias was observed. Paired t tests showed no significant difference in the UA percentages estimated with clinical DECT and micro CT (p =.2.96) (Table 3). Discussion Most studies in the literature have focused on pure stones; very few studies have included mixed stones. Graser et al. [2] investigated stone composition differentiation using a first-generation dual-source scanner operated at 8 and 14 kv. Most stones in their study were pure stones, although four mixed stones were included. Boll et al. [5] included more mixed stones together with pure UA and non-ua stones in their study. Each stone was treated as a whole, and the main goal was to differentiate pure UA, pure non- UA, and mixed stones. As a consequence, individual components inside the mixed stones were neither differentiated nor quantified. Stolzmann et al. [3, 4] used color coding with commercial DECT software to detect UA and non-ua components in both pure and mixed stones. Stones were considered to have UA Minimum Absolute Error (%) Maximum Absolute Error (%) 3 7/Sn /Sn /Sn /Sn /Sn /Sn a Across all 24 stones. b Micro CT versus dual-energy CT (t test). components if any red was observed and to have non-ua components if any blue was observed. No quantitative data were presented on the percentage of UA and non-ua content in each stone. In this study, we performed dual-energy analysis on a pixel-by-pixel basis. Each pixel inside a stone was classified as either UA or non-ua by comparison of its CT number ratio with a predetermined threshold. This allowed us to quantify UA and non-ua percentage inside the mixed stones. For first-generation dual-source DECT, 8- and 14-kV beams were used without additional filters, which may be problematic for large patients because the accuracy of stone composition differentiation decreases in large patients, mainly because of the limited penetration of the 8-kV beam [1, 15]. Thus, there was an upper limit on the size of patients who could undergo dual-energy examinations with first-generation dual-source scanners [2 5, 15]. The introduction of a tin filter in second-generation dual-source scanners and the availability of the 1-kV/ Sn14-kV scan mode improved the ability to perform DECT on large patients [15, 25 28]. In this study, we used a third-generation dual-source scanner with a total of five dualenergy scan modes available, four of which had tin filters on the high (15 kv) beam. We covered a wide range of body sizes in this study, using phantoms with lateral width from 3 to 55 cm, representing slim to very obese adult patients. We selected dual-energy scan modes based on phantom sizes: 7 and 8 kv were used for phantoms representing small and medium patients, respectively, because these modes have better spectral separation yet still provide sufficient penetration for patients of this size. We used 9 and 1 kv for phantoms representing large and obese patients, respectively, to provide sufficient penetration. p b 324 AJR:27, August 216

5 Dual-Energy CT of Urinary Stones Varying the scan modes on the basis of phantom size matched our clinical work flow, which was designed to take advantage of wider spectral separation in slim patients while obtaining better penetration in large patients. The varying scan modes, however, added complexity to the data analysis and required adjustment of the CT number ratio threshold for each dual-energy (tube potential) mode. In other words, a single UA non-ua cutoff cannot be applied to all scan modes, as shown in the results. Our results indicated that DECT can provide accurate quantification of UA and non-ua components in mixed stones at all body sizes (RMSE, %). However, even though the overall RMSE was similar for different-sized phantoms, the error of individual stones depended on phantom size (Fig. 6). In this study, we investigated selection of the CT number ratio threshold, which has substantial influence on stone composition differentiation and quantification. CT number ratio not only depends on the dual-energy scan mode used but also may depend on patient size [2]. In this study, we used RMSE, averaged over all 24 stones, as the figure of merit to determine the optimal threshold for a given dual-energy scan mode and phantom size. As expected, the optimal CT number ratio was lower for dual-energy modes with higher tube potentials for the low-energy beam. The RMSE versus CT number ratio threshold curves in Figure 5 showed wide and flat valleys around the optimal CT number ratio threshold, indicating that RMSE will not dramatically increase when the CT number ratio selected is slightly different from the optimal values. This stabilizes the selection of CT number ratio in nonideal scenarios, such as when image noise is present. One potential source of error in the dualsource, dual-energy data is the partial volume effect, which is due to the limited pixel size and resolution (.5 mm) achieved with the commercial CT scanner evaluated. The micro CT data, however, allow highly accurate quantification owing to the very high spatial resolution (.6.1 mm) and hence greatly reduced partial volume effect. The good agreement observed between the whole-body CT results and the micro CT results indicates that for the task of assessing percentage UA composition the spatial resolution of the evaluated scanner was sufficient. A range of stone sizes were included in this study, as are typically seen in patients. Visual observation of the data showed no clear relation between the magnitude of error and stone size (Fig. 6). Statistical testing for a potential relation (e.g., correlation analysis) was not performed because of the limited sample size (n = 24). There were several limitations to this study. First, it was an in vitro phantom study. Multiple stones were placed in vials and scanned at the same time. The arrangement did not emulate the stone location and perhaps orientation relative to patients. We do not believe that this presents a major concern, because accuracy and uniformity of the CT number were routinely tested and found to meet or exceed regulatory requirements. Establishing the accuracy of CT numbers ensured the consistency of CT number ratio, which was used to determine percentage stone composition. Furthermore, similar phantom designs have been used in several previous studies, which were found to agree with clinical studies [2 4, 15, 2]. Nonetheless, in vivo patient studies are warranted to fully confirm clinical accuracy and utility. The second limitation was the small number of stones owing to the limited availability of stones that had been scanned with micro CT. Third, our study focused on quantification of only UA and non-ua components in mixed stones. The substantial difference between the effective atomic numbers of UA and non-ua enabled the quantification of each component. It is of clinical interest to further differentiate and quantify different non-ua components. However, this will be a more challenging task because the difference of effective atomic numbers between non-ua components is smaller than that between UA and non-ua components. Finally, the results of our study can be applied only to the dual-energy scan modes and scanner evaluated, that is, a thirdgeneration dual-source scanner. The quantification accuracy of scanners that do not have a tin filter or the evaluated tube potential combinations (i.e., first- and second-generation dualsource scanners) or of scanners that entail different dual-energy acquisition techniques (e.g., voltage switching or dual-layer detectors) requires further investigation. Conclusion In phantom studies, accurate quantification of UA and non-ua components in mixed stones is possible with DECT. References 1. Primak AN, Fletcher JG, Vrtiska TJ, et al. Noninvasive differentiation of uric acid versus non-uric acid kidney stones using dual-energy CT. Acad Radiol 27; 14: Graser A, Johnson TR, Bader M, et al. Dual energy CT characterization of urinary calculi: initial in vitro and clinical experience. Invest Radiol 28; 43: Stolzmann P, Kozomara M, Chuck N, et al. In vivo identification of uric acid stones with dual-energy CT: diagnostic performance evaluation in patients. Abdom Imaging 21; 35: Stolzmann P, Scheffel H, Rentsch K, et al. Dualenergy computed tomography for the differentiation of uric acid stones: ex vivo performance evaluation. Urol Res 28; 36: Boll DT, Patil NA, Paulson EK, et al. Renal stone assessment with dual-energy multidetector CT and advanced postprocessing techniques: improved characterization of renal stone composition pilot study. Radiology 29; 25: Kulkarni NM, Eisner BH, Pinho DF, Joshi MC, Kambadakone AR, Sahani DV. 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6 Leng et al. filtration can improve the differentiation of non- large body size using dual-energy dual-source com- 26. Primak AN, Ramirez Giraldo JC, Liu X, Yu L, uric acid renal stones: an ex vivo phantom study. puted tomography. Eur Radiol 213; 23: McCollough CH. Improved dual-energy material AJR 211; 196: Krambeck AE, Khan NF, Jackson ME, Lingeman discrimination for dual-source CT by means of 16. Zilberman DE, Ferrandino MN, Preminger GM, JE, McAteer JA, Williams JC Jr. Inaccurate report- additional spectral filtration. Med Phys 29; Paulson EK, Lipkin ME, Boll DT. In vivo deter- ing of mineral composition by commercial stone 36: mination of urinary stone composition using dual energy computerized tomography with advanced post-acquisition processing. J Urol 21; 184: Coe FL, Parks JH, Asplin JR. The pathogenesis and treatment of kidney stones. N Engl J Med 1992; 327: Daudon M, Donsimoni R, Hennequin C, et al. Sex- and age-related composition of calculi analyzed by infrared spectroscopy. Urol Res 1995; 23: Kasidas GP, Samuell CT, Weir TB. Renal stone analysis: why and how? Ann Clin Biochem 24; 41: Qu M, Jaramillo-Alvarez G, Ramirez-Giraldo JC, et al. Urinary stone differentiation in patients with A A analysis laboratories: implications for infection and metabolic stones. J Urol 21; 184: Zarse CA, McAteer JA, Sommer AJ, et al. Nondestructive analysis of urinary calculi using micro computed tomography. BMC Urol 24; 4: Pramanik R, Asplin JR, Jackson ME, Williams JC Jr. Protein content of human apatite and brushite kidney stones: significant correlation with morphologic measures. Urol Res 28; 36: Williams JC Jr, McAteer JA, Evan AP, Lingeman JE. Micro-computed tomography for analysis of urinary calculi. Urol Res 21; 38: Primak AN, Giraldo JC, Eusemann CD, et al. Dual-source dual-energy CT with additional tin filtration: dose and image quality evaluation in phantoms and in-vivo. AJR 21; 195: B B 27. Stolzmann P, Leschka S, Scheffel H, et al. Characterization of urinary stones with dual-energy CT: improved differentiation using a tin filter. Invest Radiol 21; 45: Thomas C, Krauss B, Ketelsen D, et al. Differentiation of urinary calculi with dual energy CT: effect of spectral shaping by high energy tin filtration. Invest Radiol 21; 45: McCollough CH, Bruesewitz MR, Kofler JM Jr. CT dose reduction and dose management tools: overview of available options. RadioGraphics 26; 26: Duan X, Wang J, Qu M, et al. Kidney stone volume estimation from computerized tomography images using a model based method of correcting for the point spread function. J Urol 212; 188: Fig. 1 Example of ability to differentiate uric acid and calcium salts using micro CT. A, Photograph shows stone on millimeter-scale background. B, Micro CT slice through stone shows stone is composed of uric acid (UA), which has characteristically low x-ray attenuation value, and calcium oxalate monohydrate (COM). Infrared spectroscopy of cohort stones was used to verify minerals. This stone was scanned at 9-µm voxel size. Segmentation of UA and non-ua portions of stone yielded 32% UA and 68% non-ua. Distinction between UA and non-ua components is so clear that accurate measurement of proportion of UA in stone is easy and accurate. Fig. 2 Photographs show experimental setup. A and B, Each stone was placed in individual waterfilled vial (A), and all vials were attached to plastic stand and placed into center of water phantom (B) for CT. 326 AJR:27, August 216

7 Dual-Energy CT of Urinary Stones A D Fig. 3 Example of stone analysis. A C, Low-energy (A) and high-energy (B) CT images show mixed stone with 49% uric acid (UA) and 51% non-ua content as identified with micro CT and corresponding CT number ratio map (C). D F, Composition maps show UA in red and non-ua content in blue with CT number ratio thresholds of 1.1 (D), 1.55 (E), and 1.7 (F). Error of UA estimation was 46% (D), 6% (E), and 26% (F) in comparison with values obtained with micro CT. B E C F AJR:27, August

8 Leng et al. A C B D Fig. 4 Dual-energy CT quantification of stone composition. A and B, Micro CT images of two stones show 49% uric acid (UA), 51% non-ua (A) and 43% UA, 57% non-ua (B). C and D, Mixed dual-energy CT images correspond to A and B. E and F, Dual-energy CT composition maps corresponding to A and B show 54% UA, 46% non-ua (E), and 53% UA, 47% non-ua (F). E F 328 AJR:27, August 216

9 Dual-Energy CT of Urinary Stones RMSE Error in % UA cm 7/Sn15 35 cm 7/Sn15 4 cm 8/Sn15 45 cm 9/Sn15 5 cm 1/Sn15 55 cm 1/Sn15 t* = 1.28 t* = CT Number Ratio Stone 3 cm 35 cm 4 cm Fig. 5 Graph shows variation of root-mean-square error (RMSE) as CT number ratio threshold is varied. CT number ratio thresholds are shown for different phantom sizes and dual-energy scan modes. Optimal CT number ratio threshold corresponding to minimal RMSE depends on phantom size and dual-energy mode. Optimal thresholds (t*) for 3- and 55-cm phantoms are indicated Fig. 6 Graphs show error of uric acid (UA) estimation for each stone at different phantom sizes. Stones are presented in order of increasing volume; stone 1 is smallest and stone 24 largest. Stone 45 cm 5 cm 55 cm Phantom Size AJR:27, August