Abstract
Objective:
To study the application of using low energy images combined with adaptive statistical iterative reconstruction (ASiR) in dual-energy spectral CT portal venography (CTPV) to reduce iodine load.
Methods:
41 patients for CTPV were prospectively and randomly divided into two groups. Group A ( n = 21) used conventional 120 kVp scanning protocol with contrast dose at 0.6 gI/kg while group B ( n = 20) used dual-energy spectral imaging with reduced contrast dose at 0.3 gI/kg. The 120 kVp images in Group A and 50 keV images in Group B were reconstructed with 40% ASiR. The contrast-to-noise ratio of portal vein was calculated. The image quality and the numbers of intrahepatic portal vein branches were evaluated by two experienced radiologists using a 5-point scoring system.
Results:
Group B reduced iodine load by 52% compared to Group A (17.21 ± 3.30 gI vs 35.80 ± 6.18 gI, p < 0.001). All images in both groups were acceptable for diagnosis. CT values and standard deviations in portal veins of Group B were higher than Group A (all p < 0.05); There were no statistical differences in contrast-to-noise ratio, image quality score and the number of observed portal vein branches between the two groups (all p > 0.05), and the two observers had excellent agreement in image quality assessment (all κ > 0.75).
Conclusion:
The use of 50 keV images in dual-energy spectral CTPV with ASiR reduces total iodine load by 52% while maintaining good image quality.
Advances in knowledge:
Spectral CT images combined with ASiR can be used in low contrast dose CTPV portal venography to maintain image quality and reduce contrast dose.
Introduction
CT portal venography (CTPV) is a widely used noninvasive imaging method which can display the portal vein and its branches, it can help to evaluate the dilation degree of portal vein and collateral vascular structures, morphology and the relationship with the surrounding tissues in patients with portal hypertension, it can also assess the portal vein patency of liver transplantation patients,1,2 as well as the degree of invasion of abdominal malignant tumors to the veins.
The contrast agent returned to the portal vein system via pulmonary circulation and systemic circulation after it was injected in the CTPV examination. The process lasts for a long time, and the concentration of contrast agent decreases after systemic circulatory metabolism, which affects the degree of enhancement in portal vein and its branches. Therefore, patients will be continuously injected with high concentration of contrast agent to maintain the peak plateau period of vascular enhancement, which may result in excessive iodine load to patients. Although the acute side effects of contrast agents have been significantly reduced, the long-term adverse reactions are gradually increased, in which the contrast-induced nephropathy (CIN) is particularly prominent.3 If the patient is accompanied by diabetes and renal insufficiency, the incidence rate of CIN can be more than 19%,4 which is associated with mortality and morbidity of patients5,6 and is also the third leading cause of hospital acquired renal failure.7,8 Previous studies have shown that the dose of contrast agent is an independent risk factor for CIN.9 Therefore, reducing the iodine load by improving the examination technique can benefit the patients.
Previous studies have shown that the dual-energy spectral CT images can be used to reduce the iodine load in CT angiography, such as for imaging coronary artery,10 pulmonary artery,11 abdominal aorta12 and peripheral artery.13 Researchers have also demonstrated the use of 60 keV monochromatic images in dual-energy spectral CTPV for reducing iodine loads.14 According to the principle of dual-spectral CT imaging, even though the target vessels at lower energy levels have higher contrast, the image noise also increases simultaneously,15 which may affect the diagnosis of the disease to certain extent. Iterative reconstruction algorithms, such as the adaptive statistical iterative reconstruction (ASiR) algorithm, can effectively reduce image noise.16,17 The purpose of this study was to investigate the clinical application of further reduce the patient iodine contrast load using even lower energy images in dual-energy spectral CTPV combined with the ASiR algorithm.
Methods
Ethical approval
This single-site prospective study was approved by the institutional review board and written informed consents were received from all patients before CTPV examination.
Patients
Patients came for CTPV from May 2016 to February 2017 were prospectively enrolled and randomly divided into Groups A and B. Group A used the standard patient weight-dependent contrast dosage at 0.6 gI/kg while group B use a lower contrast dosage at 0.3 gI/kg. Exclusion criteria included: (1) pregnant females and minors; (2) patients with allergy to iodine contrast medium; (3) hyperthyroidism (4) severe liver and kidney dysfunction; (5) severe non-compensatory cardiac insufficiency. Finally, a total of 41 patients were included with 21 cases in Group A and 20 cases in Group B. Detailed patient characteristics are listed in Table 1.
Table 1.
The patient characteristics comparison between the two groups
| Parameters | Group A (n = 21) | Group B (n = 20) | Test value | p-value |
| Basic information | ||||
| Gender (female/male) | 7/14 | 6/14 | 0.053 a | 1.000b |
| Age (years) | 58.71 ± 10.47 | 64.00 ± 10.19 | 1.637 | 0.110 |
| Weight (kg) | 59.67 ± 10.31 | 57.35 ± 10.99 | −0.697 | 0.490 |
| Height (cm) | 166.76 ± 6.54 | 166.95 ± 9.92 | 0.072 | 0.943 |
| BMI (kg·m−2) | 21.46 ± 3.70 | 20.54 ± 3.34 | −0.831 | 0.411 |
| Medical history | ||||
| Chronic hepatitis/cirrhosis/liver cancer | 10/21 (47.6%) | 6/20 (30.0%) | 1.977 a | 0.372 |
| Other abdominal tumors | 8/21 (38.1%) | 12/20 (60.0%) | ||
| Other diseases* | 3/21 (14.3%) | 2/20 (10.0%) | ||
| Portal vein diameter | ||||
| MPV (mm) | 14.60 ± 2.88 | 13.60 ± 2.47 | −1.202 | 0.237 |
| LPV (mm) | 11.81 ± 2.10 | 11.12 ± 1.91 | −1.114 | 0.272 |
| RPV (mm) | 10.98 ± 1.74 | 11.20 ± 1.62 | 0.411 | 0.683 |
| Portal vein disease | ||||
| Portal hypertension | 9/21 (42.9%) | 6/20 (30.0%) | 0.730 a | 0.393 |
| Cancer embolus | 3/21 (14.3%) | 3/20 (15.0%) | 0.004 a | 1.000b |
| Thrombus | 1/21 (4.8%) | 2/20 (10.0%) | 0.414 a | 0.606b |
BMI, body mass index; MPV, main portal vein; LPV, left branch of portal vein; RPV, right branch of portal vein
For the χ2 value, bFor the Fisher exact probabilities method.
*Stomachache (n = 1), gastritis (n = 1) and epilepsia (n = 1) in Group A, Cholelithiasis (n = 1) and right parapelvic cyst (n = 1) in Group B.
Data acquisition and reconstruction
All scans were performed on a 64-slice CT scanner (Discovery CT 750 HD, GE Healthcare, Milwaukee, WI, USA). The preparations before scanning were in accordance with the conventional upper abdominal enhancement imaging. Patients were scanned in supine position while holding their breath, and the scanning range was from the diaphragmatic dome to the inferior margin of liver in the craniocaudal direction. Group A was scanned using a conventional scan protocol (120 kVp, automatic tube current modulation (Smart mA) for obtaining noise index of 10 Hounsfield unit at 5 mm slice thickness) while group B was scanned using a dual-energy spectral CT imaging mode with scan protocols approximating the radiation dose of the conventional 120 kVp protocol. Both groups used 64*0.625 mm detector collimation for scanning. Patients were injected with non-ionic iodinated contrast agent (Ioversol, 350 mg I/mL, Jiangsu Hengrui Medicine Co. Ltd., China) via the antecubital vein with indwelling needle (22G) by using a power injector (Missouri XD2001, Ulrich medical, Buchbrunnenweg, Ulm, Germany). Patient weight-dependent contrast dosages were used: 0.6 gI/kg for Group A and 0.3 gI/kg for Group B. After the contrast injection, 40 ml normal saline was injected for washing. The total contrast injection time was 30 s with injection rates adjusted based on the required contrast volume plus 40 ml normal saline. So, for a patient with weight of 65 kg in group B, the contrast volume would be 55.7 ml = 65 kg*0.3 gI/kg/350 mgI ml−1, resulting in an injection rate of 3.2 ml s−1 = (55.7 ml + 40 ml)/30 s). The portal venous phase scan started 60 s after the start of the contrast agent injection. After scanning, the data in Group A were reconstructed with 40% ASiR at 1.25 mm slice thickness to obtain conventional 120 kVp images while the data in Group B were reconstruction with 40% ASiR at 1.25 mm slice thickness to obtain 50 keV images. The 40% ASiR was chosen to balance the spatial resolution and image noise. These images are transferred into an advanced workstation (AW4.6, GE Healthcare) for post-processing and analysis. The parameters of scanning, contrast agent injection and reconstruction for the two groups are shown in Table 2.
Table 2.
The parameters of scanning, contrast agent injection and reconstruction for the two groups
| Parameters | Group A (n = 21) | Group B (n = 20) |
| Scanning parameters | ||
| Tube voltage (kVp) | 120 | 80/140 rapid-switching |
| Tube current (mA) | smart mA (NI = 10) | Personalized selection based on NI = 10 |
| Rotation rate (s·r−1) | 0.6 | Based on the scanning protocol |
| Pitch | 1.375:1 | 1.375:1 |
| Scan field of view (cm) | 50 | 50 |
| Collimation(mm) | 64*0.625 | 64*0.625 |
| Injection parameters | ||
| Iodine load (gI) | weight (kg)*0.6 gI/kg | weight (kg)*0.3 gI/kg |
| Normal saline (ml) | 40 | 40 |
| Total injection time (s) | 30 | 30 |
| Injection rate (ml·s−1) | 4.77 ± 0.62 | 3.00 ± 0.31 |
| Reconstruction parameters | ||
| Thickness (mm) | 1.25 | 1.25 |
| Reconstructed images | 120 kVp images | 50 keV images |
| Algorithm | 40% ASiR | 40% ASiR |
NI, noise index.
Data measurement and calculation
Objective parameters
The diameters of the main portal vein, left and right branches of each patient were measured by one radiologist (YXL, with 4 years of experience in CT abdominal imaging). The regions of interest (ROIs) were drawn in the lumen of the main portal vein, left branch of portal vein, right branch of portal vein (RPV), as well as on liver parenchyma, subcutaneous fat and erector spinae at the same measured level on the axial sectional images in each patient to measure their CT attenuation values and standard deviations (SD). The above ROIs were selected from the slice with the largest lumen and were carefully placed to avoid the edge and filling defect of the vessels. Measurements were repeated by placing ROI again on the above and below slices. The average value was calculated from the measurements from the three consecutive slices. Previous studies have used the SD of subcutaneous fat or erector spinae at the same measured level of the vessel as the background noise. In this study, a pre-calculation was performed determine the more stable SD measurement to use as the background noise by calculating the coefficient of variation (CV) of SD measurement for both subcutaneous fat and erector spinae: CV= (SD measurement)/mean SD measurement)*100%, and determined that the SD of erector spinae had smaller CV and was more stable to be used as the background noise. The contrast-to-noise ratio (CNR) of extrahepatic and intrahepatic portal veins were calculated using the following quiations:
where ROIv and ROIl represent the CT number of the portal vein and liver parenchyma, respectively, and ROIe and SDe represent the CT number and SD of the erector spinae. There was no threshold value for CNR before image review, and the values from the conventional group (Group A) were used as reference standards for comparison.
The volumetric CT dose index and dose–length product of each patient was recorded in the dose report to calculate the effective dose (ED) using the formula:
ED = DLP×K, where K = 0.015 mSv/(mGy*cm) for the abdominal region was used.
Subjective parameters
The subjective image quality score was evaluated blindly by two radiologists independently (XXC and ZLR, with 10 and 4 years of experience in CT abdominal imaging, respectively) using a 5-point scoring system. The evaluation criteria are shown in Table 3. Image quality scores below 3 were considered non-diagnostic. The observable segmental numbers of portal vein were also evaluated: each additional segmental level added one to the final score. For the image quality score, when the evaluation was inconsistent between the two radiologists, the final score was decided by the two radiologists after consulting each other. The imaging parameters for patients on workstation were hidden before evaluation.
Table 3.
Subjective evaluation criteria of CTPV image quality
| Score level | Evaluation criterion |
| 5 | Excellent image quality and opacification, can be clearly diagnosed. |
| 4 | Good image quality and opacification, can be clearly diagnosed. |
| 3 | Limited image quality and opacification, can still be diagnosed. |
| 2 | Suboptimal image quality and opacification, affect the diagnosis. |
| 1 | Poor image quality and opacification, cannot be diagnosed. |
CTPV, CT portal venography.
Statistical analysis
The above parameters were analyzed by using SPSS® v. 23.0 (IBM Corp., New York, NY; formerly SPSS Inc., Chicago, IL), with p < 0.05 indicating statistically significant difference. Continuous variables were expressed as mean ± SD, the subjective score was expressed as median (Q1, Q3). The single-sample K-S and Levene’s tests were used to test the goodness-of-fit and homogeneity of variance of the measurements, respectively. The independent samples student's t-test was used to test the parameters when data were consistent with normal distribution and homogeneity of variance, otherwise the Mann–Whitney U test was used. Categorical variables were compared by using χ 2 test or Fisher exact probabilities method. κ test was used to evaluate the consistency of subjective scores by two radiologists and the numbers of intrahepatic portal vein branches, the κ values were defined as follows: κ value >0.75, excellent agreement; 0.60–0.74, good agreement; 0.40–0.59, fair agreement; and κ value <0.40, poor agreement. Correlation analysis was performed by using Pearson correlation analysis.
Results
Patient characteristics
There were no significant differences between the two groups in patient demographic data, diameter of portal vein branches and radiation dose (all p > 0.05). Patients were with portal hypertension in 9/21 cases, cancer embolus in 3/21 cases and thrombosis in 1/21 cases in Group A while were with portal hypertension in 6/20 cases, cancer embolus in 3/20 cases and thrombosis in 2/20 cases in Group B, and there were no significant differences between the two groups (all p > 0.05), as shown in Tables 1 and 4. The iodine load in Group B (17.21 ± 3.30 gI) decreased by 52% compared to Group A (35.80 ± 6.18 gI), and the difference was statistically significant (p < 0.001), as shown in Figure 1.
Table 4.
The radiation dosage and contrast dosage comparison between the two groups
| Parameters | Group A (n = 21) | Group B (n = 20) | t-value | p-value |
| CTDIvol (mGy) | 12.76 ± 4.83 | 14.47 ± 4.81 | 1.133 | 0.264 |
| DLP (mGy·cm) | 395.05 ± 149.64 | 324.18 ± 101.41 | −1.766 | 0.085 |
| Effective dose (mSv) | 5.93 ± 2.24 | 4.86 ± 1.52 | −1.766 | 0.085 |
| Contrast load (gI) | 35.80 ± 6.18 | 17.21 ± 3.30 | −11.925 | <0.001 |
CTDIvol, volumetric CT dose index; DLP, dose–length product.
Figure 1.
Comparison of iodine load between the two groups.
The comparison of quantitative parameters
The CT attenuation values of main portal vein, LPV and RPV in Group B were higher than those in Group A, but the difference was statistically significant only in RPV (p = 0.007), and there was significant difference in the mean CT attenuation values of three veins between the two groups (p = 0.018). The CV of the SD measurement (5.80/20.18 = 28.7%) for the erector spinae was smaller than that (7.83/20.59 = 38.0%) for the subcutaneous fat and was used to represent background image noise. The SD of Group B was higher than that of Group A and the difference was statistically significant (all p < 0.05). There were no significant differences in the CNR among the three veins and between any two groups (all p > 0.05), as shown in Table 5, Figure 2.
Table 5.
Quantitative image quality comparison between the two groups
| Parameters | Group A (n = 21) | Group B (n = 20) | t-value | p-value |
| CT attenuation values(HU) | ||||
| MPV | 164.78 ± 22.71 | 184.07 ± 41.22 | 1.868 | 0.069 |
| LPV | 168.62 ± 23.13 | 186.22 ± 35.14 | 1.903 | 0.064 |
| RPV | 165.20 ± 18.23 | 191.29 ± 37.90 | 2.831 | 0.007 |
| Mean | 168.39 ± 20.27 | 188.91 ± 32.10 | 2.460 | 0.018 |
| SD (HU) | ||||
| MPV | 18.73 ± 2.82 | 21.73 ± 5.32 | 2.266 | 0.029 |
| LPV | 17.69 ± 3.18 | 20.36 ± 4.53 | 2.197 | 0.034 |
| RPV | 17.52 ± 2.77 | 22.85 ± 5.97 | 3.694 | 0.001 |
| Mean | 17.26 ± 1.98 | 21.95 ± 3.62 | 5.180 | <0.0001 |
| CNRExtrahepatic | ||||
| MPV | 6.83 ± 1.66 | 5.75 ± 2.28 | −1.728 | 0.092 |
| CNRIntrahepatic | ||||
| LPV | 3.26 ± 1.41 | 3.08 ± 1.22 | −0.433 | 0.667 |
| RPV | 3.04 ± 1.28 | 3.24 ± 1.23 | 0.519 | 0.606 |
| Mean | 3.15 ± 1.29 | 3.16 ± 1.19 | 0.032 | 0.975 |
CNR, contrast-to-noise ratio; LPV, left branch of portal vein;MPV, main portal vein; RPV, right branch of portal vein; SD, standard deviation.
Figure 2.
Bar chart for comparison of quantitative parameters between two groups. MPV, main portal vein; LPV, left branch of portal vein; RPV, right branch of portal vein; SD, standard deviation, for erector spinae. CNR, Contrast to noise ratio.
The comparison of qualitative parameters
Two radiologists had excellent consistency for the subjective image quality evaluation (κ = 0.76, p < 0.001). All images quality scores in both groups were more than three points. There was no significant difference in image quality scores between the two groups (5 (4, 5) vs 4 (4, 5), Z = −0.467, p = 0.641). Two radiologists had excellent consistency for the observable segmental numbers of the portal vein branch (κ = 0.81, p < 0.001) of the two groups. There was no significant difference in observable segmental numbers of the portal vein branch between the two groups [4 (4, 5) vs 5 (4, 5), Z = −1.192, p = 0.233]. Figure 3 provides an example of image quality comparison between the two groups.
Figure 3.
(A, B) are VR of two groups. (A) A 58-year-old male with duodenal cancer, 66 kg body weight with total iodine load of 39.60 gI. The subjective image quality score was 5, and the number of observed segmental portal veins was 5. (B) A 68-year-old female with liver cancer, 56 kg body weight with total iodine load of 16.80 gI. The subjective image quality score was 5, and the number of observed segmental portal veins was 5.
Correlation between BMI and CNR of portal vein
There was no correlation between BMI and CNR for the extrahepatic and intrahepatic portal veins of the two groups, as shown in Figure 4.
Figure 4.
Scatter plot of correlation between BMI and CNR portal vein in two groups. (A) is for Group A, and (B) is for Group B. BMI, body mass index; CNR,contrast-to-noiseratio.
Discussion
In this study, the application of using low energy images (50 keV) combined with ASiR algorithm was evaluated in dual-energy spectral CTPV for reducing iodine load to patients. The results indicated that the combination of using low energy images and ASiR significantly reduced iodine dose to patients while maintaining acceptable image quality.
The dual-energy spectral CT scanner used in this study uses single source and rapid switching between high and low voltage (140/80 kVp) in 0.5 ms to provide coherent dual-energy information. Thus, 101 sets of (40–140 keV) images can be reconstructed. These different energy level of images have different characteristics, the high-energy level images have lower CT attenuation values, lower contrast ratio and lower noise, while the low-energy level images are closer to the K edge of iodine (33 keV), so that the photoelectric effect of iodine is increased and the contrast of vessels is improved.10,17 Therefore, the use of low-energy images compensates for the decrease of contrast dose to maintain acceptable vascular enhancement for angiography with low contrast agents.10 However, as the photon energy reduces, the images noise will increase markedly at the same time,15 which will affect the imaging quality of CTPV. Therefore, balancing blood vessel contrast and image noise by selecting the optimal energy level is the key to ensure the diagnosis of portal vein disease and improve the image quality in the cases of low iodine load.
The iterative reconstruction algorithms such as ASiR algorithm can effectively reduce the image noise by analyzing the statistical characteristics of the photons in each independent measurement and comparing with the known statistical distribution and correcting in the iterative calculation process16,.18 The ASiR reconstruction algorithm takes the spatial resolution and density resolution of the image into account and generates images at a clinically acceptable reconstruction speed. ASiR provides the 0–100% weights for different clinical needs, the higher the percentage of ASiR, the lower the image noise, the smoother the image. At high ASiR percentages the image sharpness, spatial resolution and image quality may be reduced.19,20 Previous studies have shown that the spatial resolution and image noise can be balanced at about 40–50% ASiR (Maintain image spatial resolution while reducing noise).21–24 Yin et al20 also used the 40% ASiR in the study of mesenteric vessels. In this study ASiR with 40% strength was chosen for image reconstruction which was also commonly used in clinical work.
Ma et al14 presented a study of using 60 keV images combined with ASiR 50% for reducing 25% iodine dose to patients in dual-energy spectral CTPV since the application of ASiR stopped at 60 keV at the time of their study. In theory, reducing the photon energy can further increase contrast enhancement in the vessels, image noise increase is another factor that should be considered. Zhao et al25 reported that the optimal energy level for achieving the highest CNR for portal veins in dual-energy spectral CTPV without ASiR was at 51 keV. In this study, the 50 keV images with ASiR technique was selected for analysis and comparison. The combination of lower keV (lower than 60 keV) and ASiR was only made available to us in recent software upgrade. The results showed that the CT attenuation values of the 50 keV images of the three-portal veins were still higher than those of the conventional 120 kVp images even with 52% reduced iodine load. Although the image noise in Group B (with reduced iodine load) increased, the CNR of portal veins was similar to that of Group A, and there were no significant differences between the two groups in the subjective evaluation of image quality and the numbers of extrahepatic and intrahepatic portal veins.
There was no correlation between BMI and CNR of the portal veins in the two groups. This was due to the following two facts. On the one hand, the amount of contrast agent was adjusted based on the patient weight in both groups to make the enhancement in vessels (CT attenuation values) patient weight-independent. On the other hand, image noise was maintained by using smart mA technique in Group A and personalized dual-energy spectral protocol in Group B. So that patients with larger size were compensated by increased radiation dose.
There are some limitations in this study. First, 40% ASiR which was commonly used in daily routine was selected for reconstruction in this study. Further studies are required to investigate whether higher percentage ASiR provide better CNR and overall image quality. Second, patients with CTPV often have portal hypertension and the enhancement peaks of portal vein are not identical, therefore the use of a fixed delay time (60 s after injection of contrast agent) in this study may not be idea. Third, only the main branches of the portal vein were evaluated while the other veins of the portal vein system were not analyzed and evaluated (such as the superior and inferior mesenteric vein, the splenic vein, the left and right gastric veins, and the varix vein around esophagus in portal hypertension.). Finally, patients were from single center and one scanner manufacturer was utilized in this study which may lead to potential bias.
In conclusion, the use of 50 keV combined with 40% ASiR algorithm in dual-energy spectral CTPV reduces iodine dose to patients by 52% while maintaining the same image quality compared with the conventional 120 kVp scanning and contrast injection protocol.
Contributor Information
Dong Han, Email: 147690660@qq.com.
Xiaoxia Chen, Email: 1183729657@qq.com.
Yuxin Lei, Email: 772890021@qq.com.
Chunling Ma, Email: 279671444@qq.com.
Jieli Zhou, Email: 869074328@qq.com.
Yingcong Xiao, Email: 251194603@qq.com.
Yong Yu, Email: yuyongkeyan@sina.com.
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