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Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction
Clinical Radiology xxx (2017) e1ee6
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction S.-Y. Wang a, W. Gao b, Y.-M. Zhong a, *, A.-M. Sun a, Q. Wang a, L.-W. HU b, H.-S. Qiu b, J.-Y. Li c a
Diagnostic Imaging Center, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China b Department of Cardiology, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China c CT Research Center, GE Healthcare China, Bejing, PR China
art icl e i nformat ion Article history: Received 2 September 2016 Received in revised form 4 January 2017 Accepted 30 January 2017
AIM: To demonstrate the clinical value of prospective electrocardiography (ECG)-triggered cardiac computed tomography (CT) with low concentration contrast medium, low tube voltage, and adaptive statistic iterative reconstruction (ASIR) to reduce both radiation and contrast dose in examining infants with complex congenital heart disease (CHD). MATERIALS AND METHODS: Forty-four consecutive infants (19 male, 25 female, age: 8.064.33 months, weight: 7.311.36 kg) with complex CHD underwent prospective ECGtriggered low-dose cardiac CT using 80 kVp and 120 mA. The contrast agent was iodixanol (270 mg iodine/ml, Visipaque, GE Healthcare, Co. Cork, Ireland). Cardiac CT images were reconstructed with 70% ASIR. The quantitative CT image quality was assessed by image noise in adipose tissue and contrast-to-noise ratio (CNR) in the aorta. The qualitative image analysis was performed on a five-point grading scale by two independent reviewers and interobserver variability was calculated. The results of 32 CT examinations were also compared with the available surgical results for diagnostic accuracy evaluation. RESULTS: The effective dose was 0.550.10 mSv for the patient population. The iodine load was 3.950.73 g iodine. Image noise in adipose tissue was 16.241.42 HU and CNR in aorta was 21.907.10. All images were acceptable for diagnosis with an average score of 4.520.38 and good agreement between reviewers (kappa¼0.75). Compared to the surgery results in 32 cases, CT was 97% and 88% accurate diagnosing extracardiac and intracardiac defects, respectively. CONCLUSION: Prospective ECG-triggered cardiac CT using 80 kVp, low-concentration iodinated contrast agent (270 mg iodine/ml) and 70% ASIR reconstruction provides excellent image quality and accurate diagnosis for complex congenital heart disease in infants with reduced contrast medium dose and low radiation dose. Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
* Guarantor and correspondent: Y.-M. Zhong, Diagnostic Imaging Center, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China. Tel.: þ86 21 38626161 5001; fax: þ86 21 58393915. E-mail address: [email protected] (Y.-M. Zhong). http://dx.doi.org/10.1016/j.crad.2017.01.017 0009-9260/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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Introduction Congenital heart disease (CHD) in infants is a difficult area of diagnostic radiology because of the small body size and fast heart rate. Computed tomography (CT) is increasingly applied to enable clinical decision making in infants with CHD, because of its excellent spatial resolution, adequate temporal resolution, and fast acquisition time; however, radiation dose exposure from CT is of particular concern due to the possible harmful effect. Compared to adults, infants and children are more sensitive to radiation and have a longer lifespan to develop potential radiation injuries.1 Besides ionizing radiation, cardiovascular CT also involves the use of iodinated contrast agents, which are a potential source of nephrotoxic and cytotoxic effects. A recent study reported that the application of iodinated contrast agents during diagnostic radiography procedures led to a clear increase in the level of radiation-induced gene damage,2 although there is no direct evidence that it could translate to an increase in malignancy. Despite the potential risks caused by radiation and contrast medium, CT is particularly useful for the assessment of cardiovascular anomalies, especially of airway abnormalities. Recently updated CT imaging techniques such as low tube voltage and low-concentration iodinated contrast agent with iterative reconstruction algorithms such as Adaptive Statistical Iterative Reconstruction (ASIR) for image reconstruction not only reduce the radiation and contrast doses, but also aid the interpretation of CT findings.3e7 The purpose of the present study was to review the clinical values of the optimization of image acquisition protocols in cardiovascular CT with low-concentration iodinated contrast agent and low tube voltage prospective electrocardiography (ECG) triggering and ASIR for infants with complex CHD.
Material and methods Study population This is a Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant prospective research study and was approved by the institutional review board. Written informed consent was obtained from the parents of all patients for clinical imaging. A total of 44 consecutive patients were enrolled in March 2016 for the study. The inclusion criteria were infants with CHD who were scheduled for cardiac CT for further information and their body weight was between 5e10 kg. The exclusion criteria were hypersensitivity to iodine contrast medium, impaired renal function defined as creatinine clearance <60 ml/min. No patient was excluded using the exclusion criteria during the patient collection period. There were 19 male and 25 female patients. The mean age and heart rate was 8.064.33 months (range, 2e19 months) and 115.6114.15 beats/min (range, 85e141 beats/min), respectively, and the mean weight was 7.311.36 kg (range, 5.2e10 kg; Table 1).
Table 1 Clinical, image quality, iodine load, and radiation dose information in 44 cases. Clinical information Gender
5e10 kg Male Female
Age (months; meanSD) Heart rate (beats/min; meanSD) Weight (kg; meanSD) Image noise (HU) CNR Iodine load (g iodine) CTDIvol (mGy) DLP (mGy∙cm) ED (mSv)
19 25 8.064.33 115.6114.15 7.311.36 16.241.42 21.907.10 3.950.73 1.35 13.673.87 0.550.10
CT protocols All 44 patients were scanned on a 64-section highdefinition CT system (Discovery CT 750 HD, GE Healthcare, Waukesha, WI, USA) during free breathing with sedation and each patient underwent a prospective ECGtriggering paediatric cardiac CT examination. The prospective scanning sequence was as follows: step-and-shoot axial scanning and a collimation of 640.625 mm with a scan field of view of 25 cm and gantry rotation speed of 0.35 seconds; the matrix was 512 512. A tube voltage of 80 kV and tube current of 120 mA was used. The data acquisition window was 380 ms with padding technique. The centre of the data acquisition window was set at 35e45% of the ReR interval when the heart rate was >75 beats/min and at 65e85% of the ReR interval when heart rate was <75 beats/ min. All Discovery CT750HD scanners are equipped with the ASIR algorithm. ASIR is a reconstruction technique that can reduce image noise and improve image quality by modelling noise in the projections compared with the traditional filtered back-projection (FBP) reconstruction algorithm. To restore the more classic appearance of CT images, a linear blend of the traditional FBP method with ASIR has been implemented on the scanner with the blending percentage from 0% to 100%, 0% corresponding to a conventional FBP image and 100% corresponding to a pure ASIR image.3,8 In the present study, all scans were reconstructed using 70%ASIR algorithm. The non-ionic contrast agent, iodixanol, (Visipaque, 270 mg iodine/ml concentration, GE Healthcare, Co. Cork, Ireland) at a volume of 1e1.5 ml/kg was injected through a peripheral vein using a dual-head power injector at an injection rate of 0.8e2 ml/s and followed by 5e10 ml saline at the same injection rate to reduce artefacts caused by undiluted intravascular contrast agent.
Quantitative analysis of image quality The signal intensity (Hounsfield unit mean value) was measured at the aortic root and thymus with regions of interest (ROI) of 0.8e1.2 cm2 by a single reader. The noise (standard deviation [SD] of signal intensity) was measured
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
S.-Y. Wang et al. / Clinical Radiology xxx (2017) e1ee6
at the adipose tissue with ROIs of 0.8e1 cm2. The contrastto-noise ratio (CNR) for the aortic root was calculated with the equation: CNR ¼ (mean density of the aortic root-mean density of thymus)/image noise.9 The noise and CNR were used to estimate the objective image quality.
Qualitative analysis of image quality The subjective image quality was evaluated by two radiologists with more than 5 years of experience in reading cardiac CT image independently and blindly. Image quality was graded on a five-point Likert scale as follows: 5¼excellent image quality; 4¼good quality; 3¼fair quality with minor artefact; 2¼poor quality but adequate for evaluation; 1¼unacceptable image.5
Surgical results All images were diagnosed by two radiologists with >5 years of experience in reading cardiac CT images; discrepancies were resolved by independent review. The results of cardiovascular CT for 32 patients who underwent surgery were compared with the surgical findings.
Radiation dose estimation The volumetric CT dose index (CTDIvol) and doseelength product (DLP) for each patient were recorded, and the effective dose (ED) was calculated using the equation of ED¼k DLP (k is an age-dependent conversion coefficient; Table 2).10e12
Statistical analysis
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Table 3 Patient information. Cardiac defects
No. of cases
Complete atrioventricular canal Pulmonary stenosis Ventricular septal defect or atrial septal defect or patent ductus arteriosus Right aortic arch with aberrant subclavian artery Aortic valve stenosis Tetralogy of Fallot Pulmonary atresia with ventricular septal defect Pulmonary atresia with intact ventricular septum Partial or total anomaly pulmonary venous connection Single ventricle Total
2 3 17 1 3 11 2 1 3 1 44
acyanotic CHD. The acyanotic CHD included complete atrioventricular canal, pulmonary stenosis, ventricular septal defect (VSD), atrial septal defect, or patent ductus arteriosus, right aortic arch with aberrant subclavian artery, partial anomaly pulmonary venous connection, and aortic valve stenosis. The cyanotic CHD included tetralogy of Fallot (TOF), pulmonary atresia (PA) with VSD, pulmonary atresia with intact ventricular septum, total anomaly pulmonary venous connection, and single ventricle.
Quantitative analysis of image quality Quantitative analysis of image quality was assessed in terms of image noise and CNR. Image noise in adipose tissue was 16.241.42 HU (range: 13.4e19.7 HU) and CNR in aorta was 21.907.1 (range: 9.73e39.17; Table 1, Fig 1).
Qualitative analysis of image quality
Data were analysed using commercially available SPSS version 19.0 software (SPSS, Chicago, IL, USA). Continuous variables were expressed as meanSD. For the qualitative image analysis, the score of the two readers was compared by using the kappa concordance test and the agreement index was obtained. The diagnostic accuracy of cardiovascular CT was calculated by comparing with the surgical findings.
Results Patient information Patient information for the 44 patients is listed in Table 3. There were 17 cases of cyanotic CHD and 27 cases of Table 2 Normalized values of effective dose per doseelength product (DLP) over various ages. Ages (months)
Effective dose per DLP (mSv/mGy∙cm)
0e12 12e60 60e120 >120
0.039 0.026 0.018 0.013
Qualitative analysis of image quality, as assessed by the Likert scale, showed excellent image quality, the average scores were 4.530.35 and 4.510.41 from reviewers 1 and 2, respectively with good agreement between the reviewers (kappa¼0.75; Fig 1).
Diagnostic accuracy In all 44 patients, 32 patients underwent operation. Comparing to the surgery results, CT over-diagnosed patent ductus arteriosus in one patient, so the accuracy in the diagnosis of extracardiac defects was 97%. CT also misdiagnosed subaortic stenosis in two patients and atrial septal defect in one patient and mitral inadequacy in one patient, so CT was 88% accurate for intracardiac defects. In 40 of 44 cases, the coronary artery was demonstrated clearly. There were three cases of TOF or PA/VSD with the anomalous origin of coronary artery, which was diagnosed at CT (Fig 2). These CT findings were confirmed at surgery.
Radiation dose and iodine estimation The CTDIvol was 1.35 mGy and the mean DLP was 15.291.93 mGy∙cm (range: 10.1e19.96 mGy∙cm), resulting in an estimated mean effective dose (ED) of
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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Figure 1 CT views of a 64-row CT examination in an 8-month-old male patient with ASD, TOF, and right aortic arch; weight¼7 kg; iodine load¼3.78 g iodine; 80 kVp 120 mA; ASIR 70%. (a) Atrial septal defect. (b) Aortic overriding. (c) Right ventricular outflow tract stenosis. (d) Right aortic arch. Image noise in adipose tissue was 16.86 (regions of interest¼12 mm2).
0.550.1 mSv (range: 0.38e0.78 mSv). The iodine load was 3.950.73 g iodine (range, 2.81e5.4 g iodine; Table 1).
Discussion Considering the small body size and high heart rate, CHD in infants is a difficult area of diagnostic radiology. Recently, the higher spatial and adequate temporal resolution of multidetector-row CT (MDCT) has evolved and is applied in CHD to achieve a precise diagnosis13,14; however, high radiation exposure and high concentration of iodine are the major concerning issues in cardiovascular CT angiography. Ionizing radiation, such as X-rays, can create hydroxyl radicals with water molecules, which in turn interact with nearby DNA to cause strand breaks or damage. This situation is more obvious in children, because they are at more risk than adults from a given dose of radiation and also have more remaining years of life during which a radiationinduced cancer could develop.15 In addition, the application of iodinated contrast agents further increases the
peripheral lymphocyte DNA radiation damage, which may enhance cancer generation,16 and is also a risk factor of contrast-induced nephropathy.17,18 Therefore, CT applied in infants represents a challenge regarding radiation and iodinated contrast medium dose, so reducing the radiation dose and the incidence and severity of contrast media side effects has become the main focus in many studies.6,19,20 Shin et al.6 reported that the combination of lowconcentration contrast media and a low tube-voltage technique together with iterative reconstruction is a feasible method that provides sufficient contrast enhancement and image quality at CT aortography in adults. Many studies have described the use of low tube voltage prospective ECG-triggering to effectively reduce radiation dose. Liu et al.21 reported achieving the average DLP and ED values of 19.897.38 mGy∙cm and 1.270.34 mSv, respectively, in cardiac CT performed on the same scanner used in the present study. Koplay et al.22 reported results with prospective ECG-gated high-pitch dual-source cardiac CT, and the average DLP and ED values were 15.69.6 mGy∙cm and 0.340.1 mSv, respectively. In the present study, the use
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
S.-Y. Wang et al. / Clinical Radiology xxx (2017) e1ee6
Figure 2 CT images of an 11-month-old female patient with TOF and ASD. (a)Oblique maximum intensity projection reconstruction MSCT images and (b) oblique volume-rendered reconstruction MSCT image demonstrate the right coronary artery arising (black arrow) from the left main coronary artery (hollow arrow) passing between the pulmonary artery and ascending aorta. AAO, ascending aorta; RCA, right coronary artery; MPA, main pulmonary artery.
of a tube voltage of 80 kV and tube current of 120 mA ensured a low radiation dose. The mean DLP was 15.291.93 mGy∙cm and the mean ED was 0.550.10 mSv, which was lower than that of Liu et al.21 and similar to that of Koplay et al.22.
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Low-dose imaging techniques may reduce image quality due to increased noise and increase susceptibility to beamhardening artefacts23 to which ASIR has been proposed as a possible solution.3e7 In the present study, a high degree of ASIR (70%ASIR) was applied to reduce image noise. The image noise and CNR in the present study was 16.241.42 HU and 21.907.10, respectively, which was better than that reported in previous reports on adults.24 As to the qualitative analysis of image quality, the average scores were 4.530.35 and 4.510.41 from reviewers 1 and 2 with very good agreement between the radiologists, which was good enough for diagnosis. High-concentration contrast media in conventional cardiovascular CT protocols in infants is usually preferred, but may lead to radiocontrast-induced nephropathy and may enhance cancer generation. Using low concentration contrast medium with a lower tube voltage, which helps to improve vascular attenuation, image quality is acceptable, especially without any change to the injection rate or total contrast medium volume.25 Recently, the use of a minimal dose of low-osmolar or iso-osmolar contrast medium was emphasized by the European Society of Urogenital Radiology contrast media safety committee guidelines.26 The 270 mg iodine/ml concentration of iodixanol, as an isoosmotic contrast medium with a low iodine concentration and low viscosity, reduced the contrast medium dose by 27.03% compared with the 370 mg iodine/ml concentration iodixanol. In the present study, the mean iodine load was 3.950.73 g iodine, similar to the previous literature report.21 Complex CHD is defined as CHD with more than one separate cardiovascular anomaly. Patients are initially evaluated using echocardiography in the conventional diagnostic algorithm for infant complex CHD; however, according to the current literature, even in first-class cardiovascular centres, the diagnostic accuracy with echocardiography is only approximately 80%.27,28 Misdiagnoses after echocardiography could potentially be corrected at cardiovascular CT, especially in extracardiac defects, such as coarctation, total anomalous pulmonary venous connection, patent ductus arteriosus, etc. In the present study, the accuracy of CT in the diagnosis for extracardiac defects and intracardiac defects was 97% and 88%, respectively, when compared to surgery, which was higher than the 80% for diagnosis at echocardiography. Due to the high incidence (11%) of coronary artery abnormalities with CHD,29 assessment of the coronary arteries in the infant population is necessary, especially when coronary variations are important for decision of the surgical approach, such as TOF. Prospective ECG-triggering CT can show the origin of the coronary artery clearly. In the present study, the origin of the coronary artery was shown clearly in all of patients with TOF and was confirmed at surgery. In addition, CT might prove to be a better method for identifying cardiovascular anomalies, tracheal anomalies, and lung lesions simultaneously. There are also several limitations to the present study. First, this study only selected 44 infants as research subjects, thus the data have to be interpreted with caution
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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given the small sample size. Second, the evaluation of image quality was a subjective process; however, the good kappa values for the interobserver agreement in the present study indicated that the image quality was consistent. In conclusion, complex CHD in infants is a difficult area in diagnostic radiology. Prospective ECG-triggered cardiac CT, as a non-invasive imaging technique, using 80 kVp, lowconcentration iodinated contrast agent (270 mg iodine/ ml), and 70%ASIR reconstruction provides excellent image quality and accurate diagnosis for complex CHD in infants with reduced contrast medium and radiation doses.
References 1. Pierce DA, Shimizu Y, Preston DL, et al. Studies of the mortality of atomic bomb survivors. Report 12, part I. Cancer: 1950-1990. 1996. Radiat Res 2012;178:AV61e87. 2. Piechowiak EI, Peter JF, Kleb B, et al. Intravenous iodinated contrast agents amplify DNA radiation damage at CT. Radiology 2015;275:692e7. 3. Mieville FA, Gudinchet F, Rizzo E, et al. Paediatric cardiac CT examinations: impact of the iterative reconstruction method ASIR on image qualitydpreliminary findings. Pediatr Radiol 2011;41:1154e64. 4. Schafer ML, Ludemann L, Boning G, et al. Radiation dose reduction in CT with adaptive statistical iterative reconstruction (ASIR) for patients with bronchial carcinoma and intrapulmonary metastases. Clin Radiol 2016;71:442e9. 5. Leipsic J, Labounty TM, Heilbron B, et al. Adaptive statistical iterative reconstruction: assessment of image noise and image quality in coronary CT angiography. AJR Am J Roentgenol 2010;195:649e54. 6. Shin HJ, Kim SS, Lee JH, et al. Feasibility of low-concentration iodinated contrast medium with lower-tube-voltage dual-source CT aortography using iterative reconstruction: comparison with automatic exposure control CT aortography. Int J Cardiovasc Imaging 2016;32(Suppl. 1):S53e61. 7. Pontana F, Pagniez J, Duhamel A, et al. Reduced-dose low-voltage chest CT angiography with Sinogram-affirmed iterative reconstruction versus standard-dose filtered back projection. Radiology 2013;267:609e18. 8. Tumur O, Soon K, Brown F, et al. New scanning technique using Adaptive Statistical Iterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT. J Med Imaging Radiat Oncol 2013;57:292e6. 9. Hausleiter J, Martinoff S, Hadamitzky M, et al. Image quality and radiation exposure with a low tube voltage protocol for coronary CT angiography results of the PROTECTION II Trial. JACC Cardiovasc Imaging 2010;3:1113e23. 10. The 2007 recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP 2007;37(2e4): 1e332. 11. Geleijns J, Golding S, Menzel HG, et al. A workshop on quality criteria for computed tomography held in Arhus, Denmark, November 1998. Eur Radiol 2000;10:544e5. 12. Thomas KE, Wang B. Age-specific effective doses for pediatric MSCT examinations at a large children’s hospital using DLP conversion coefficients: a simple estimation method. Pediatr Radiol 2008;38:645e56.
13. Chan FP, Hanneman K. Computed tomography and magnetic resonance imaging in neonates with congenital cardiovascular disease. Semin Ultrasound CT MR 2015;36:146e60. 14. Tsai IC, Chen MC, Jan SL, et al. Neonatal cardiac multidetector row CT: why and how we do it. Pediatr Radiol 2008;38:438e51. 15. Brenner DJ, Hall EJ. Computed tomographydan increasing source of radiation exposure. N Engl J Med 2007;357:2277e84. 16. Singh S, Kalra MK, Gilman MD, et al. Adaptive statistical iterative reconstruction technique for radiation dose reduction in chest CT: a pilot study. Radiology 2011;259:565e73. 17. Traub SJ, Kellum JA, Tang A, et al. Risk factors for radiocontrast nephropathy after emergency department contrast-enhanced computerized tomography. Acad Emerg Med 2013;20:40e5. 18. Toprak O. Risk markers for contrast-induced nephropathy. Am J Med Sci 2007;334:283e90. 19. Chen CM, Chu SY, Hsu MY, et al. Low-tube-voltage (80 kVp) CT aortography using 320-row volume CT with adaptive iterative reconstruction: lower contrast medium and radiation dose. Eur Radiol 2014;24:460e8. 20. Oda S, Utsunomiya D, Yuki H, et al. Low contrast and radiation dose coronary CT angiography using a 320-row system and a refined contrast injection and timing method. J Cardiovasc Comput Tomogr 2015;9:19e27. 21. Liu Z, Song L, Yu T, et al. Application of low dose radiation and low concentration contrast media in enhanced CT scans in children with congenital heart disease. Int J Clin Pract 2016 Sep;70(Suppl. 9B):B22e8. http://dx.doi.org/10.1111/ijcp.12857. 22. Koplay M, Kizilca O, Cimen D, et al. Prospective ECG-gated high-pitch dual-source cardiac CT angiography in the diagnosis of congenital cardiovascular abnormalities: radiation dose and diagnostic efficacy in a pediatric population. Diagn Interv Imaging 2016;97:1141e50. 23. Zheng M, Zhao H, Xu J, et al. Image quality of ultra-low-dose dual-source CT angiography using high-pitch spiral acquisition and iterative reconstruction in young children with congenital heart disease. J Cardiovasc Comput Tomogr 2013;7:376e82. 24. Annoni AD, Andreini D, Pontone G, et al. Ultra-low-dose CT for left atrium and pulmonary veins imaging using new model-based iterative reconstruction algorithm. Eur Heart J Cardiovasc Imaging 2015; 16:1366e73. 25. Brooks RA. A quantitative theory of the Hounsfield unit and its application to dual energy scanning. J Comput Assist Tomogr 1977;1:487e93. 26. Stacul F, van der Molen AJ, Reimer P, et al. Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 2011;21:2527e41. 27. Soongswang J, Nana A, Laohaprasitiporn D, et al. Limitation of transthoracic echocardiography in the diagnosis of congenital heart diseases. J Med Assoc Thai 2000;83(Suppl. 2):S111e7. 28. Tworetzky W, McElhinney DB, Brook MM, et al. Echocardiographic diagnosis alone for the complete repair of major congenital heart defects. J Am Coll Cardiol 1999;33:228e33. 29. Hong C, Becker CR, HUber A, et al. ECG-gated reconstructed multidetector row CT coronary angiography: effect of varying trigger delay on image quality. Radiology 2001;220:712e7.
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction S.-Y. Wang a, W. Gao b, Y.-M. Zhong a, *, A.-M. Sun a, Q. Wang a, L.-W. HU b, H.-S. Qiu b, J.-Y. Li c a
Diagnostic Imaging Center, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China b Department of Cardiology, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China c CT Research Center, GE Healthcare China, Bejing, PR China
art icl e i nformat ion Article history: Received 2 September 2016 Received in revised form 4 January 2017 Accepted 30 January 2017
AIM: To demonstrate the clinical value of prospective electrocardiography (ECG)-triggered cardiac computed tomography (CT) with low concentration contrast medium, low tube voltage, and adaptive statistic iterative reconstruction (ASIR) to reduce both radiation and contrast dose in examining infants with complex congenital heart disease (CHD). MATERIALS AND METHODS: Forty-four consecutive infants (19 male, 25 female, age: 8.064.33 months, weight: 7.311.36 kg) with complex CHD underwent prospective ECGtriggered low-dose cardiac CT using 80 kVp and 120 mA. The contrast agent was iodixanol (270 mg iodine/ml, Visipaque, GE Healthcare, Co. Cork, Ireland). Cardiac CT images were reconstructed with 70% ASIR. The quantitative CT image quality was assessed by image noise in adipose tissue and contrast-to-noise ratio (CNR) in the aorta. The qualitative image analysis was performed on a five-point grading scale by two independent reviewers and interobserver variability was calculated. The results of 32 CT examinations were also compared with the available surgical results for diagnostic accuracy evaluation. RESULTS: The effective dose was 0.550.10 mSv for the patient population. The iodine load was 3.950.73 g iodine. Image noise in adipose tissue was 16.241.42 HU and CNR in aorta was 21.907.10. All images were acceptable for diagnosis with an average score of 4.520.38 and good agreement between reviewers (kappa¼0.75). Compared to the surgery results in 32 cases, CT was 97% and 88% accurate diagnosing extracardiac and intracardiac defects, respectively. CONCLUSION: Prospective ECG-triggered cardiac CT using 80 kVp, low-concentration iodinated contrast agent (270 mg iodine/ml) and 70% ASIR reconstruction provides excellent image quality and accurate diagnosis for complex congenital heart disease in infants with reduced contrast medium dose and low radiation dose. Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
* Guarantor and correspondent: Y.-M. Zhong, Diagnostic Imaging Center, Shanghai Children’s Medical Center Affiliated with Shanghai Jiao Tong University Medical School, No. 1678 Dong Fang Road, Shanghai 200127, PR China. Tel.: þ86 21 38626161 5001; fax: þ86 21 58393915. E-mail address: [email protected] (Y.-M. Zhong). http://dx.doi.org/10.1016/j.crad.2017.01.017 0009-9260/Ó 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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S.-Y. Wang et al. / Clinical Radiology xxx (2017) e1ee6
Introduction Congenital heart disease (CHD) in infants is a difficult area of diagnostic radiology because of the small body size and fast heart rate. Computed tomography (CT) is increasingly applied to enable clinical decision making in infants with CHD, because of its excellent spatial resolution, adequate temporal resolution, and fast acquisition time; however, radiation dose exposure from CT is of particular concern due to the possible harmful effect. Compared to adults, infants and children are more sensitive to radiation and have a longer lifespan to develop potential radiation injuries.1 Besides ionizing radiation, cardiovascular CT also involves the use of iodinated contrast agents, which are a potential source of nephrotoxic and cytotoxic effects. A recent study reported that the application of iodinated contrast agents during diagnostic radiography procedures led to a clear increase in the level of radiation-induced gene damage,2 although there is no direct evidence that it could translate to an increase in malignancy. Despite the potential risks caused by radiation and contrast medium, CT is particularly useful for the assessment of cardiovascular anomalies, especially of airway abnormalities. Recently updated CT imaging techniques such as low tube voltage and low-concentration iodinated contrast agent with iterative reconstruction algorithms such as Adaptive Statistical Iterative Reconstruction (ASIR) for image reconstruction not only reduce the radiation and contrast doses, but also aid the interpretation of CT findings.3e7 The purpose of the present study was to review the clinical values of the optimization of image acquisition protocols in cardiovascular CT with low-concentration iodinated contrast agent and low tube voltage prospective electrocardiography (ECG) triggering and ASIR for infants with complex CHD.
Material and methods Study population This is a Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant prospective research study and was approved by the institutional review board. Written informed consent was obtained from the parents of all patients for clinical imaging. A total of 44 consecutive patients were enrolled in March 2016 for the study. The inclusion criteria were infants with CHD who were scheduled for cardiac CT for further information and their body weight was between 5e10 kg. The exclusion criteria were hypersensitivity to iodine contrast medium, impaired renal function defined as creatinine clearance <60 ml/min. No patient was excluded using the exclusion criteria during the patient collection period. There were 19 male and 25 female patients. The mean age and heart rate was 8.064.33 months (range, 2e19 months) and 115.6114.15 beats/min (range, 85e141 beats/min), respectively, and the mean weight was 7.311.36 kg (range, 5.2e10 kg; Table 1).
Table 1 Clinical, image quality, iodine load, and radiation dose information in 44 cases. Clinical information Gender
5e10 kg Male Female
Age (months; meanSD) Heart rate (beats/min; meanSD) Weight (kg; meanSD) Image noise (HU) CNR Iodine load (g iodine) CTDIvol (mGy) DLP (mGy∙cm) ED (mSv)
19 25 8.064.33 115.6114.15 7.311.36 16.241.42 21.907.10 3.950.73 1.35 13.673.87 0.550.10
CT protocols All 44 patients were scanned on a 64-section highdefinition CT system (Discovery CT 750 HD, GE Healthcare, Waukesha, WI, USA) during free breathing with sedation and each patient underwent a prospective ECGtriggering paediatric cardiac CT examination. The prospective scanning sequence was as follows: step-and-shoot axial scanning and a collimation of 640.625 mm with a scan field of view of 25 cm and gantry rotation speed of 0.35 seconds; the matrix was 512 512. A tube voltage of 80 kV and tube current of 120 mA was used. The data acquisition window was 380 ms with padding technique. The centre of the data acquisition window was set at 35e45% of the ReR interval when the heart rate was >75 beats/min and at 65e85% of the ReR interval when heart rate was <75 beats/ min. All Discovery CT750HD scanners are equipped with the ASIR algorithm. ASIR is a reconstruction technique that can reduce image noise and improve image quality by modelling noise in the projections compared with the traditional filtered back-projection (FBP) reconstruction algorithm. To restore the more classic appearance of CT images, a linear blend of the traditional FBP method with ASIR has been implemented on the scanner with the blending percentage from 0% to 100%, 0% corresponding to a conventional FBP image and 100% corresponding to a pure ASIR image.3,8 In the present study, all scans were reconstructed using 70%ASIR algorithm. The non-ionic contrast agent, iodixanol, (Visipaque, 270 mg iodine/ml concentration, GE Healthcare, Co. Cork, Ireland) at a volume of 1e1.5 ml/kg was injected through a peripheral vein using a dual-head power injector at an injection rate of 0.8e2 ml/s and followed by 5e10 ml saline at the same injection rate to reduce artefacts caused by undiluted intravascular contrast agent.
Quantitative analysis of image quality The signal intensity (Hounsfield unit mean value) was measured at the aortic root and thymus with regions of interest (ROI) of 0.8e1.2 cm2 by a single reader. The noise (standard deviation [SD] of signal intensity) was measured
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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at the adipose tissue with ROIs of 0.8e1 cm2. The contrastto-noise ratio (CNR) for the aortic root was calculated with the equation: CNR ¼ (mean density of the aortic root-mean density of thymus)/image noise.9 The noise and CNR were used to estimate the objective image quality.
Qualitative analysis of image quality The subjective image quality was evaluated by two radiologists with more than 5 years of experience in reading cardiac CT image independently and blindly. Image quality was graded on a five-point Likert scale as follows: 5¼excellent image quality; 4¼good quality; 3¼fair quality with minor artefact; 2¼poor quality but adequate for evaluation; 1¼unacceptable image.5
Surgical results All images were diagnosed by two radiologists with >5 years of experience in reading cardiac CT images; discrepancies were resolved by independent review. The results of cardiovascular CT for 32 patients who underwent surgery were compared with the surgical findings.
Radiation dose estimation The volumetric CT dose index (CTDIvol) and doseelength product (DLP) for each patient were recorded, and the effective dose (ED) was calculated using the equation of ED¼k DLP (k is an age-dependent conversion coefficient; Table 2).10e12
Statistical analysis
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Table 3 Patient information. Cardiac defects
No. of cases
Complete atrioventricular canal Pulmonary stenosis Ventricular septal defect or atrial septal defect or patent ductus arteriosus Right aortic arch with aberrant subclavian artery Aortic valve stenosis Tetralogy of Fallot Pulmonary atresia with ventricular septal defect Pulmonary atresia with intact ventricular septum Partial or total anomaly pulmonary venous connection Single ventricle Total
2 3 17 1 3 11 2 1 3 1 44
acyanotic CHD. The acyanotic CHD included complete atrioventricular canal, pulmonary stenosis, ventricular septal defect (VSD), atrial septal defect, or patent ductus arteriosus, right aortic arch with aberrant subclavian artery, partial anomaly pulmonary venous connection, and aortic valve stenosis. The cyanotic CHD included tetralogy of Fallot (TOF), pulmonary atresia (PA) with VSD, pulmonary atresia with intact ventricular septum, total anomaly pulmonary venous connection, and single ventricle.
Quantitative analysis of image quality Quantitative analysis of image quality was assessed in terms of image noise and CNR. Image noise in adipose tissue was 16.241.42 HU (range: 13.4e19.7 HU) and CNR in aorta was 21.907.1 (range: 9.73e39.17; Table 1, Fig 1).
Qualitative analysis of image quality
Data were analysed using commercially available SPSS version 19.0 software (SPSS, Chicago, IL, USA). Continuous variables were expressed as meanSD. For the qualitative image analysis, the score of the two readers was compared by using the kappa concordance test and the agreement index was obtained. The diagnostic accuracy of cardiovascular CT was calculated by comparing with the surgical findings.
Results Patient information Patient information for the 44 patients is listed in Table 3. There were 17 cases of cyanotic CHD and 27 cases of Table 2 Normalized values of effective dose per doseelength product (DLP) over various ages. Ages (months)
Effective dose per DLP (mSv/mGy∙cm)
0e12 12e60 60e120 >120
0.039 0.026 0.018 0.013
Qualitative analysis of image quality, as assessed by the Likert scale, showed excellent image quality, the average scores were 4.530.35 and 4.510.41 from reviewers 1 and 2, respectively with good agreement between the reviewers (kappa¼0.75; Fig 1).
Diagnostic accuracy In all 44 patients, 32 patients underwent operation. Comparing to the surgery results, CT over-diagnosed patent ductus arteriosus in one patient, so the accuracy in the diagnosis of extracardiac defects was 97%. CT also misdiagnosed subaortic stenosis in two patients and atrial septal defect in one patient and mitral inadequacy in one patient, so CT was 88% accurate for intracardiac defects. In 40 of 44 cases, the coronary artery was demonstrated clearly. There were three cases of TOF or PA/VSD with the anomalous origin of coronary artery, which was diagnosed at CT (Fig 2). These CT findings were confirmed at surgery.
Radiation dose and iodine estimation The CTDIvol was 1.35 mGy and the mean DLP was 15.291.93 mGy∙cm (range: 10.1e19.96 mGy∙cm), resulting in an estimated mean effective dose (ED) of
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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Figure 1 CT views of a 64-row CT examination in an 8-month-old male patient with ASD, TOF, and right aortic arch; weight¼7 kg; iodine load¼3.78 g iodine; 80 kVp 120 mA; ASIR 70%. (a) Atrial septal defect. (b) Aortic overriding. (c) Right ventricular outflow tract stenosis. (d) Right aortic arch. Image noise in adipose tissue was 16.86 (regions of interest¼12 mm2).
0.550.1 mSv (range: 0.38e0.78 mSv). The iodine load was 3.950.73 g iodine (range, 2.81e5.4 g iodine; Table 1).
Discussion Considering the small body size and high heart rate, CHD in infants is a difficult area of diagnostic radiology. Recently, the higher spatial and adequate temporal resolution of multidetector-row CT (MDCT) has evolved and is applied in CHD to achieve a precise diagnosis13,14; however, high radiation exposure and high concentration of iodine are the major concerning issues in cardiovascular CT angiography. Ionizing radiation, such as X-rays, can create hydroxyl radicals with water molecules, which in turn interact with nearby DNA to cause strand breaks or damage. This situation is more obvious in children, because they are at more risk than adults from a given dose of radiation and also have more remaining years of life during which a radiationinduced cancer could develop.15 In addition, the application of iodinated contrast agents further increases the
peripheral lymphocyte DNA radiation damage, which may enhance cancer generation,16 and is also a risk factor of contrast-induced nephropathy.17,18 Therefore, CT applied in infants represents a challenge regarding radiation and iodinated contrast medium dose, so reducing the radiation dose and the incidence and severity of contrast media side effects has become the main focus in many studies.6,19,20 Shin et al.6 reported that the combination of lowconcentration contrast media and a low tube-voltage technique together with iterative reconstruction is a feasible method that provides sufficient contrast enhancement and image quality at CT aortography in adults. Many studies have described the use of low tube voltage prospective ECG-triggering to effectively reduce radiation dose. Liu et al.21 reported achieving the average DLP and ED values of 19.897.38 mGy∙cm and 1.270.34 mSv, respectively, in cardiac CT performed on the same scanner used in the present study. Koplay et al.22 reported results with prospective ECG-gated high-pitch dual-source cardiac CT, and the average DLP and ED values were 15.69.6 mGy∙cm and 0.340.1 mSv, respectively. In the present study, the use
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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Figure 2 CT images of an 11-month-old female patient with TOF and ASD. (a)Oblique maximum intensity projection reconstruction MSCT images and (b) oblique volume-rendered reconstruction MSCT image demonstrate the right coronary artery arising (black arrow) from the left main coronary artery (hollow arrow) passing between the pulmonary artery and ascending aorta. AAO, ascending aorta; RCA, right coronary artery; MPA, main pulmonary artery.
of a tube voltage of 80 kV and tube current of 120 mA ensured a low radiation dose. The mean DLP was 15.291.93 mGy∙cm and the mean ED was 0.550.10 mSv, which was lower than that of Liu et al.21 and similar to that of Koplay et al.22.
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Low-dose imaging techniques may reduce image quality due to increased noise and increase susceptibility to beamhardening artefacts23 to which ASIR has been proposed as a possible solution.3e7 In the present study, a high degree of ASIR (70%ASIR) was applied to reduce image noise. The image noise and CNR in the present study was 16.241.42 HU and 21.907.10, respectively, which was better than that reported in previous reports on adults.24 As to the qualitative analysis of image quality, the average scores were 4.530.35 and 4.510.41 from reviewers 1 and 2 with very good agreement between the radiologists, which was good enough for diagnosis. High-concentration contrast media in conventional cardiovascular CT protocols in infants is usually preferred, but may lead to radiocontrast-induced nephropathy and may enhance cancer generation. Using low concentration contrast medium with a lower tube voltage, which helps to improve vascular attenuation, image quality is acceptable, especially without any change to the injection rate or total contrast medium volume.25 Recently, the use of a minimal dose of low-osmolar or iso-osmolar contrast medium was emphasized by the European Society of Urogenital Radiology contrast media safety committee guidelines.26 The 270 mg iodine/ml concentration of iodixanol, as an isoosmotic contrast medium with a low iodine concentration and low viscosity, reduced the contrast medium dose by 27.03% compared with the 370 mg iodine/ml concentration iodixanol. In the present study, the mean iodine load was 3.950.73 g iodine, similar to the previous literature report.21 Complex CHD is defined as CHD with more than one separate cardiovascular anomaly. Patients are initially evaluated using echocardiography in the conventional diagnostic algorithm for infant complex CHD; however, according to the current literature, even in first-class cardiovascular centres, the diagnostic accuracy with echocardiography is only approximately 80%.27,28 Misdiagnoses after echocardiography could potentially be corrected at cardiovascular CT, especially in extracardiac defects, such as coarctation, total anomalous pulmonary venous connection, patent ductus arteriosus, etc. In the present study, the accuracy of CT in the diagnosis for extracardiac defects and intracardiac defects was 97% and 88%, respectively, when compared to surgery, which was higher than the 80% for diagnosis at echocardiography. Due to the high incidence (11%) of coronary artery abnormalities with CHD,29 assessment of the coronary arteries in the infant population is necessary, especially when coronary variations are important for decision of the surgical approach, such as TOF. Prospective ECG-triggering CT can show the origin of the coronary artery clearly. In the present study, the origin of the coronary artery was shown clearly in all of patients with TOF and was confirmed at surgery. In addition, CT might prove to be a better method for identifying cardiovascular anomalies, tracheal anomalies, and lung lesions simultaneously. There are also several limitations to the present study. First, this study only selected 44 infants as research subjects, thus the data have to be interpreted with caution
Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017
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given the small sample size. Second, the evaluation of image quality was a subjective process; however, the good kappa values for the interobserver agreement in the present study indicated that the image quality was consistent. In conclusion, complex CHD in infants is a difficult area in diagnostic radiology. Prospective ECG-triggered cardiac CT, as a non-invasive imaging technique, using 80 kVp, lowconcentration iodinated contrast agent (270 mg iodine/ ml), and 70%ASIR reconstruction provides excellent image quality and accurate diagnosis for complex CHD in infants with reduced contrast medium and radiation doses.
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Please cite this article in press as: Wang S-Y, et al., Prospective ECG-triggering cardiac CT for infants with complex congenital heart disease using low-dose contrast medium, low tube voltage, and adaptive statistical iterative reconstruction, Clinical Radiology (2017), http://dx.doi.org/ 10.1016/j.crad.2017.01.017