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Original Research |
1 Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN
55905.
2 Division of Biostatistics, Mayo Clinic, Rochester, MN.
Received September 14, 2007;
accepted after revision November 28, 2007.
A. N. Primak, O. P. Dzyubak, J. G. Fletcher, and C. H. McCollough receive
partial research funding from a grant from Siemens Medical Solutions, whose
equipment and software were used in the study.
Abstract
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MATERIALS AND METHODS. Twenty urinary stones of different sizes (1.4–4.2 mm in short-axis diameter) were placed in plastic containers. The containers were consecutively filled with different concentrations of iodine solution (21, 43, 64, 85, and 107 mg/dL; CT attenuation value range, 510–2,310 H at 120 kVp). Dual-energy CT was repeated with 80–140 and 100–140 kVp pairs, two collimation–slice thickness combinations, and the presence or absence of a 4-cm-thick oil gel around the phantom. The iodine-subtraction virtual unenhanced images were reconstructed using commercial software. The images were evaluated by three radiologists in consensus for the visibility of the stones and the presence of residual nonsubtracted iodine. Stone visibility rates were compared between the 80–140 and 100–140 kVp pairs and the five different iodine concentrations.
RESULTS. Stone visibility rates with the 80–140 kVp pair were 99%, 93%, 96%, 94%, and 3% and those with the 100–140 kVp pair were 98%, 95%, 99%, 94%, and 99% for an iodine concentration of 21, 43, 64, 85, and 107 mg/dL, respectively. The poor visibility rate with 80–140 kVp and 107 mg/dL iodine concentration was due to the failure of iodine subtraction.
CONCLUSION. Dual-energy CT iodine-subtraction virtual unenhanced technique is capable of depicting urinary stones in iodine solutions of a diverse range of concentrations in a phantom study.
Keywords: dual-energy CT • genitourinary imaging • iodine-subtraction imaging technique • reconstructed images • urinary stones
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The use of dual-source CT scanners has been shown to be effective in improving temporal resolution in coronary CT angiography [4, 6–8]. Subtraction of bone or calcium plaques from vessels on CT angiography using the dual-energy CT technique also appears promising [4]. Outside the realm of cardiovascular imaging, little experimentation with current dual-energy scanning techniques and subtraction imaging has been performed.
As a routine component of CT urograms for hematuria or suspected urothelial tumor, unenhanced scans are routinely obtained mainly to evaluate for the presence of urinary stones, and pyelographic phase scans are obtained after administration of iodinated contrast material to evaluate for the presence of urothelial carcinoma [9–12]. If virtual unenhanced scans reconstructed from pyelographic phase scans would allow the detection of urinary stones by means of automated subtraction of the iodine from the collecting system and ureters, one of the main purposes of unenhanced scans could be achieved without obtaining true unenhanced scans.
Thus, the purpose of our investigation was to evaluate the feasibility of virtual unenhanced images reconstructed from a dual-energy CT scan for the detection of urinary stones in iodine solutions in a phantom study.
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Slope from the best-fit linear regression line (CT attenuation value = A x iodine concentration + B), where A is slope and B is intercept, was calculated for each kVp pair scan, and the ratios of the two slopes—referred to as the "dual-energy ratios" [A (80 kVp) / A (140 kVp)] and [A (100 kVp) / A (140 kVp)]—were calculated.
Phantom Study
Twenty urinary stones of different compositions were used in this phantom
study: seven uric acid stones, seven calcium hydroxyapatite stones, and six
calcium oxalate stones. Each stone was placed in a 5 x 20 mm plastic
container, and the container was filled with either saline or one of the five
different concentration iodine solutions used in the calibration scan
(Fig. 1). The plastic
containers were placed in a renal proxy made from pork meat arranged in four
rows of five containers. The long axes of the plastic containers were
perpendicular to the CT gantry plane. The renal proxy was placed in a 32-cm
water bath to simulate the attenuation of the body cavity
(Fig. 2).
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The saline in all the plastic containers was then replaced with the lowest concentration iodine solu tion (i.e., 21 mg/dL). Dual-energy CT scans of the phantom were obtained using various scanning parameters: 80–140 kVp pair and 100–140 kVp pair; and collimation of 14 x 1.2 mm with reconstruction slice width of 1.5 mm and collimation of 64 x 0.6 mm with reconstruction slice width of 1.0 mm. These scans were obtained through the phantom without and with a 4-cm-thick oil gel (Superflab, Radiation Product Design) surrounding the phantom to simu late a large patient (Fig. 2). The acquisition time of the CT scan to cover a 13-cm-long kidney phantom includ ing stones in containers was approximately 6 seconds.
Automatic exposure control (CaseDose4D, GE Healthcare) was used with quality reference mAs values of 100 mAs for 140 kVp, 275 mAs for 100 kVp, and 425 mAs for 80 kVp. These values were chosen to approximate the noise levels of the three different voltage settings. The image reconstruction kernel was D30, and the reconstruction field of view was 24 cm. Thus, eight scans (two different kVp pairs x two different collimation–slice thickness combi nations x without and with a thick oil gel surrounding the phantom) were obtained for a single iodine concentration solution in the container. These scans were then repeated each time after refilling all the containers with a different iodine concentration solution in a consecutive fashion (43, 64, 85, and 107 mg/dL). Therefore, a total of 40 data sets were obtained.
Iodine-Subtraction Virtual Unenhanced Image Reconstruction
Iodine-subtraction virtual unenhanced images were reconstructed for each of
the 40 scans obtained on an independent workstation (Syngo Multi Modality
Workplace, Siemens Medical Solutions) using commercially available software
(Syngo, Dual Energy Viewer, Siemens Medical Solutions). Reconstruction took
less than 1 minute per series. For reconstruction of the 80–140 kVp
dual-energy scan sets, which was the vendor's recommended dual-energy pair,
the default dual-energy ratio (2.00) was used. For reconstruction of the
100–140 kVp dual-energy scan sets, the DICOM data tag of the 100-kVp
scan had to be modified to 80 kVp because the software accepted only the
80–140 kVp pair. The dual-energy ratio also had to be adjusted for
optimal iodine subtraction, and the data from the calibration scan were
used.
Image Interpretation
Forty iodine-subtraction virtual unenhanced image sets, each with the 20
stones, were reviewed by three abdominal radiologists in consensus who were
blinded to the scanning parameters, the concentration of the iodine solution,
and the composition of the stones. Images were reviewed on a workstation
(Advantage Window 4.2, GE Healthcare) using a multiplanar reconstruction. The
default display window width and level settings were 1,000 and 200 H,
respectively, but the reviewers were allowed to change the window settings as
necessary. Radiologists evaluated for visibility of the stones (n =
20 stones x 8 sets of scanning parameters x 5 sets of iodine
concentrations = 800 observations). When evaluating each data set to determine
stone visibility, readers placed the virtual unenhanced image on one screen
and the true unenhanced image on an adjacent screen to ensure that detected
high attenuation was, indeed, the real stone. Each image set (n = 40)
was also evaluated for the presence of nonsubtracted iodine within the con
tainers (1, no residual iodine; 2, mild; 3, moderate; 4, severe).
Statistical Analysis
Stone visibility rates were compared between scans obtained with
80–140 and 100–140 kVp pairs and with different iodine
concentration solutions used to fill the containers across other different
scanning parameters (two different collimation–slice thickness
combinations x without and with a thick oil gel surrounding the phantom)
and 20 different stones. The mean scores of nonsubtracted iodine within the
containers were calculated for the 80–140 and 100–140 kVp pairs
and with different iodine concentrations across other different scanning
parameters (two different collimation–slice thickness combinations
x without and with a thick oil gel surrounding the phantom). This was
performed to identify outliers. After excluding outliers, scanning parameters
(i.e., 80–140 or 100–140 kVp pair, collimation of 0.6 or 1.2 mm,
with or without a 4-cm-thick oil gel around the phantom), the iodine
concentration of the solutions, and the stone size (short-axis diameter) and
composition (uric acid, calcium hydroxyapatite, or calcium oxalate) were also
analyzed to determine whether they affected the stone visibility rate.
Univariate and multivariate logistic regression analyses were performed using
generalized estimating equations to account for the correlated data. A
p value of less than 0.05 was considered statistically
significant.
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Phantom Study
The size of the stones measured on the reference scan (i.e., single-energy
120-kVp scan) ranged from 1.5 to 4.2 mm (mean, 2.8 mm) in short-axis diameter
and from 2.6 to 6.4 mm (mean, 4.4 mm) in long-axis diameter. The mean
short-axis diameter for uric acid stones, calcium hydroxyapatite stones, and
calcium oxalate stones were 2.7, 2.8, and 3.0 mm, respectively. CT attenuation
of the stones measured on the reference scan at 120 kVp ranged from 242 to 863
H (mean, 590 H) for uric acid stones, from 732 to 2,422 H (mean, 1,541 H) for
calcium hydroxyapatite stones, and from 784 to 1,529 H (mean, 1,185 H) for
calcium oxalate stones.
Stone visibility rates and the mean nonsubtracted iodine score with regard to the different kVp pairs and iodine concentration solutions are summarized in Tables 1 and 2 (Fig. 3A, 3B, 3C, 3D, 3E). The poor visibility rate with the combination of 80–140 kVp and 107 mg/dL iodine concentration was due to failure of iodine subtraction (high nonsubtracted iodine). Consequently, CT scans obtained with the 80–140 kVp pair and the highest iodine concentration (107 mg/dL) were excluded as an outlier in univariate and multivariate analyses of scanning parameters, iodine concentrations of solutions, and stone size and composition if they affected the stone visibility rate. Using univariate logistic regression analysis, we found that larger stone size (p < 0.0001) and a narrower collimation of 0.6 mm (p = 0.02) were associated with a higher stone visibility rate. Stone compositions, the presence or absence of a 4-cm-thick oil gel around the phantom, kVp setting, and urine density did not influence the stone visibility rate (p > 0.05). Using multivariate analysis, larger stone size (p = 0.0005), narrow collimation of 0.6 mm (p = 0.001), and the absence of a 4-cm-thick oil gel around the phantom (p = 0.03) were associated with a higher stone visibility rate. Stone compositions, kVp, and urine density did not influence the stone visibility rate (p > 0.05). All stones that were 3 mm or larger in short-axis diameter were visible, and 92% of the stones that were smaller than 3 mm in short-axis diameter were visible.
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A small collimation was associated with a higher stone visibility rate probably because less partial volume artifact along the z-axis enabled more accurate measurement of CT attenuation of the stones and iodine, thus successfully separating them. The absence of a 4-cm-thick oil gel around the phantom was associated with a higher stone visibility rate with multivariate analysis but not with univariate analysis.
An advantage of the 80–140 kVp pair over the 100–140 kVp pair is a wider separation of the dual-energy ratio between iodine and urinary stones or other soft tissue. Disadvantages of the 80–140 kVp are saturation of CT attenuation at a high iodine concentration and higher image noise with the 80-kVp scan given the same exposure because of the effect of photon depletion. Scans of large patients or scans through the pelvis may potentially benefit from the 100–140 kVp pair; but our study failed to show an advantage of the 100–140 kVp pair except at the highest iodine concentration.
Virtual unenhanced images detected 92% of the stones that were less than 3 mm and 100% of the stones that were 3 mm or larger in short-axis diameter in this phantom study when the scans obtained with the combination of an iodine concentration of 107 mg/dL and the 80–140 kVp pair were excluded. Some of the small stones were not visible, probably because small stones were oversubtracted as iodine or there was residual undersubtracted iodine surrounding the small stones with the virtual unenhanced iodine-subtraction technique. Is this visibility rate for small stones acceptable in a clinical setting? Although most ureteral stones less than 3 mm pass spontaneously [13], detection of such stones is often clinically important. Small intrarenal stones seldom cause symptoms, but they can be the cause of microscopic hematuria. The technique needs further investigation and refinement.
The stone visibility rate was not affected by stone composition in this phantom study. The dual-energy ratio of stones at imaging with the 80–140 kVp pair was 1.12 for uric acid stones, 1.60 for calcium oxalate stones, and 1.69 for calcium hydroxyapatite stones from a previous study [14], whereas that of iodine solution was 2.19. Theoretically, the larger the separation of the dual-energy ratio of a stone and iodine, the easier it is to separate a stone from iodine.
When implementing this technique in a clinical study, one must be aware that oversaturation of the CT attenuation with high-concentration iodine may cause breakdown of the iodine-subtraction algorithm. Attention must be paid to avoid oversaturation of the CT attenuation of more than 3,000 H while still providing adequate opacification and distention of the collecting system to allow detection of tumors as filling defects. The CT attenuation of iodine solution reaches 3,000 H at 80 kVp with an iodine concentration of 75.3 mg/dL, which corresponds to approximately 1,650 H at 120 kVp. Options to decrease the concentration of iodine in the urinary tract may include the use of the split contrast material injection technique, with a smaller dose of contrast material administered for the first of two injections [10, 15], and the use of vigorous hydration or diuretics [16, 17]. The other option is to use the 100–140 kVp pair instead of the 80–140 kVp pair.
Dual-energy CT performed after the administration of iodinated contrast material has the potential to characterize enhancement of a renal mass using virtual unenhanced technique (Graser A et al. and Carter CL et al., presented at the 2007 annual meeting of the Radiological Society of North America). Therefore, virtual unenhanced images reconstructed from pyelographic phase CT urograms have the potential to detect urinary stones and to characterize a renal mass without obtaining a true unenhanced CT scan. If unenhanced CT could be eliminated from CT urography, the radiation dose to the patient could be reduced. The radiation dose of a dual-energy scan at 80–140 kVp is comparable to that of a single-energy scan at 120 kVp to achieve similar image quality or noise level [5].
Some physical limitations of the scanner that we used need to be taken into account. Currently, the second tube and detector have a maximum field of view of 26 cm in the gantry plane. The primary tube and detector have a full 40-cm field of view. Because of this configuration, the dual-energy iodine-subtraction virtual unenhanced images have a maximum field of view of 26 cm. The scanning area needs to be carefully positioned to ensure full coverage of the kidneys, ureters, and bladder using anteroposterior and lateral topograms.
In conclusion, dual-energy CT iodine-subtraction virtual unenhanced images are capable of depicting urinary stones in iodine solution. The dual-energy CT iodine-subtraction technique requires further optimization and validation with a clinical study.
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