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Dual-source Computed Tomography for Evaluating Pulmonary Artery and Aorta in Pediatric Patients with Single Ventricle

To explore the accuracy of main pulmonary artery (MPA) and ascending aorta (AAO) image evaluation in pediatric patients with single ventricle (SV) by comparing dual-source computed tomography (DSCT) with echocardiography. Thirty-one children with SV were retrospectively enrolled. The stenosis, dilation, and location of MPA and AAO were independently evaluated by DSCT and echocardiography. The accompanying arterial malformations were also assessed by DSCT. For 17 patients undergoing cardiac catheterization, the DSCT-based diameters of MPA and AAO were correlated with their pressures as measured by catheterization. Referring to the surgical and catheterization findings, DSCT had better diagnostic performance in detecting the stenosis, dilation, and location of MPA and AAO with higher sensitivity than echocardiography (sensitivity, MPA: 88.0% vs. 80.0%, AAO: 100% vs. 66.7%, great arteries location: 95.7% vs. 95.2%). The correlations between diameters of MPA and AAO with their pressures were 0.399 (p = 0.04) and 0.611 (p = 0.01), respectively. In addition, DSCT detected 23 cases with patent ductus arteriosus, 26 systemic-to-pulmonary collaterals, 9 branch pulmonary distortions, and 4 coronary artery anomalies. DSCT is reliable for assessing the anatomic features of pulmonary artery and aorta in SV children, and provides comprehensive information for surgical strategy-making.


Results
Baseline characteristics. There were no significant differences in age, weight, height, or body surface area between the SV patients and control subjects in our study (all p > 0.05) ( Table 1). The mean diameter of MPA by DSCT in patients(0.81 ± 0.36 cm) was smaller than control subjects(1.56 ± 0.18 cm) and the diameter of AAO is larger in patients(1.93 ± 0.22 cm) than control subjects(1.52 ± 0.20 cm).The stage II operation was the most common surgery conducted in SV patients (15,48.4%). The anatomic types of SV in the 31 patients consisted of single left ventricle (n = 10, 32.3%), single right ventricle (n = 11, 35.5%), and undifferentiated ventricle (n = 10, 32.3%) (Fig. 1). After confirmation at surgery or by catheterization, the locations of MPA and AAO (n = 26) included normal arrangements (n = 3, 11.5%), right-sided aortic arch (n = 15, 57.7%), and left-sided aortic arch (n = 8, 30.8%). Three (9.7%) cases of AAO dilation, three (9.7%) of MPA atresia, 19 (61.3%) of MPA stenosis, and three (9.7%) of MPA dilation were verified among the 31 patients. Correlation between DSCT-based artery diameter and artery pressure. In the patients undergoing catheterization, the mean values of DSCT-based diameters (n = 17) of MPA and AAO were 1.07 ± 0.41 cm and 2.19 ± 0.66 cm, respectively. Mean pressures (n = 27, 10 patients had measurements both before and after oxygen inhalation) of MPA and AAO were 18.81 ± 13.41 mmHg and 62.15 ± 10.93 mmHg, respectively. Weak correlation was found between MPA diameter and its pressure (r = 0.399, p = 0.04) and moderate correlation was found between AAO diameter and pressure (r = 0.611; p = 0.01).

Discussion
SV describes a set of congenital cardiac malformations characterized by both atria draining entirely, or almost entirely, into one functionally single ventricular chamber 1 . Influenced by the concurrence of different cardiovascular malformations, the physiology and clinical features vary in different patients depending on circulatory hemodynamics and the ventricular burden. Anomaly of the great arteries is one of the key factors requiring assessment prior to surgery.  Among several image modalities for CHD assessment, DSCT has specific benefits for pediatric patients. For example, equipped with two independent tubes and detectors, DSCT increases the acquisition speed and image quality, reducing the need for general anesthesia 7 and heart motion artifacts 8,9 . In addition, the radiation exposure is simultaneously decreased by taking several measures such as low tube voltage, ECG-based tube, and heart rhythm adaptive pitch 10 . The accuracy of DSCT for detecting intra-cardiac and extra-cardiac lesions has been well-described in various complex CHDs 4-6 . When applied to SV, we also found that DSCT gave accurate information on not only intra-cardiac structures, diagnosing the SV anatomic type, but also the extra-cardiac great arteries to aid in surgical planning.
The stage I operation for SV patients includes different procedures for different cardiovascular malformations, while information regarding the presence or absence of PA atresia, obstruction, and dilation plays a key role in procedure selection 1 . Moreover, the PA stenosis caused by preliminary interventions also needs to be corrected during stage II and III surgeries 11,12 . As previous studies have shown, TTE exhibited poor performance in PA stenosis detection due to the interference of lung tissue 3 , and computed tomography angiography was equally accurate in assessing PA anatomy compared with chatheterization and surgery 7,9,13 . Similar to these studies, our data indicated that DSCT had a better diagnostic performance than TTE in the detection of MPA stenosis or dilation, with a sensitivity of 88.0% vs. 80.0%.
Of equal importance, aortic dysplasia in SVs must be reconstructed using the Norwood procedure; and recoarctation increases the risk of mortality and morbidity and should be treated in following treatments 1,11,12 . According to earlier research 3,14 , TTE reliably evaluated aortic coarctation. We further confirmed that DSCT was more accurate than TTE in the evaluation of AAO in SV, with higher sensitivity and specificity (ranging 92.9-100%) than TTE (50.0-66.7%). However, poor agreement was observed between TTE and the reference standard in detecting AAO dilatation, but good agreement for DSCT was documented in this present study. This discrepancy might be explained by the fact that there was only dilation, with no coarctation of AAO in the recruited patients, and TTE underestimated arterial measurements and had the limitation of operator dependence 3,7 .
Clinically, the location of the great arteries is also important for preoperative artery assessment. We concluded that DSCT gave better definition in locating MPA and AAO compared with TTE. More importantly, DSCT is able to reconstruct 3D images of extra-cardiac vessels, reflecting the positional relationship of them more intuitively to surgeons.
Apart from the anatomy of the great arteries, hemodynamics, including artery pressure, are also taken into consideration before SV surgery 1,11 . In a recent meta-analysis, there was an association between the diameter ratio of MPA to AAO and PA pressure, and CT-based diameter ratio measurement may play an important role in aiding diagnosis of pulmonary hypertension 15 . Our data also revealed the correlation between the DSCT-based diameter of arteries and their pressures, and demonstrated that the diameter of an artery is an influencing factor on arterial pressure; this association also exists in SV. Thus, DSCT has the potential to offer information reflecting whether pulmonary hypertension exists in patients with SV.
The advantages of computed tomography angiography in describing arterioles have been widely accepted 8,16 . We found that DSCT was able to detect some accompanying arterial malformations of clinical importance while conducting assessment of the great arteries. PDA and coronary artery anomalies should be taken into consideration in formulating the surgical strategy 11,12,17 . Systemic-to-pulmonary collaterals may lengthen the recovery time and their detection should prompt embolization intervention 18,19 . In addition, PA distortion is an independent risk factor for patient mortality 20 . In summary, the detection of the existence of these anomalies by DSCT provides valuable information for interventional planning and outcome prediction of SV.
Our study had several limitations. First, because SV is a rare class of CHD, our single-center study is not based on a large number of patients. Further multi-center research is necessary for larger sample enrollment. Second, the pediatric population is sensitive to the diagnostic radiation exposure. In this study, we took several measures to reduce radiation exposure, which was much lower than that for catheterization. It will be possible to further decrease this dose with methods such as perspective ECG-gated scanning mode. Third, our study did not include follow-up outcomes, and these will be documented in a future study.
In conclusion, DSCT has the ability to give a more reliable assessment of the pulmonary artery and aorta than TTE which are vital in surgical planning in pediatric patients with SV, and simultaneously provides additional arterial information valuable to clinical interventions.

Methods and Materials
Study population. From January 2010 to November 2016, a total of 53 pediatric SV patients in our hospital were retrospectively enrolled by searching our Cardiovascular Program database, and the inclusion criteria were in accordance with the ACC/AHA 2008 Guidelines 21 . The exclusion criteria included poor image quality (n = 6, 11.3%) or incomplete clinical data (n = 16, 30.2%) and finally 31 patients (18 males, 13 females) who underwent both TTE and DSCT examinations remained. We simultaneously recruited 40 pair-matched control subjects (22  This study was conducted with the approval of the Institutional Review Board of our hospital (No. 14-163). Guardians of all the patients gave written informed consent prior to the examinations, having been informed of potential adverse reactions to the iodinated contrast agent and radiation. The participants' names and other HIPAA identifiers had been removed from all sections of the manuscript, including supplementary information.
Dual-source computed tomography. All scanning was conducted on a DSCT scanner (Somatom Definition Flash; Siemens Medical Solutions, Forchheim, Germany). Subjects younger than 6 years were given a short-acting sedative (chloral hydrate at a concentration of 10%, 0.5 ml/kg) prior to the examinations. Older patients were trained to hold their breath during scanning. The acquisition parameters of the ECG-gated protocol were as follows: tube voltage of 80 kV, tube current of 100 mAs, gantry rotation time of 0.28 s, and pitch of 0.2-0.5 (selected according to the heart rate, a higher pitch was used for higher heart rates). The ECG-pulsing window was set on Auto. The scanning scope was from the thoracic inlet to 2 cm below the level of the diaphragm in the craniocaudal direction. During angiography, nonionic contrast agent (iopamidol, 370 mg/ml; Bracco, Italy) was given at a rate of 1.2-2.5 ml/s via an antecubital vein, followed by 20 ml of saline solution at the same flow rate. The injected volume was based on body weight (1.5 ml/kg). Bolus tracking was used in the region of interest (ROI) in the descending aorta with a predefined threshold of 100 HU. Image acquisition was triggered following a delay of 5 s when the ROI attenuation threshold reached 100 HU. Data processing was performed on a workstation (Syngo; Siemens Medical System, Forchheim, Germany). The images were reconstructed with a slice thickness of 0.75 mm and an increment of 0.7 mm.
Trans-thoracic echocardiography. All patients underwent the echocardiography examination with a Philips SONOS 7500 ultrasound system (Philips Medical Systems, Bothell, WA). Established protocols for TTE, including M-mode, two-dimensional, continuous wave, and color Doppler flow imaging, were performed according to the recommendations of the American Society of Echocardiography Committee 22 . The interval between DSCT and TTE was less than 9 days. Image analysis. The DSCT assessments were conducted by two experienced radiologists, blinded to each other's diagnoses, within a three-day period. The measurements of MPA and AAO diameters were at sites 1 cm above the PA valve and aortic sinus, respectively 22 (Fig. 3). Using the mean diameters of MPA and AAO of control subjects as a contrast standard, the DSCT-based diameters of both arteries in patients were compared with the control values: MPA stenosis was defined as <75% contrast standard 3,23 and MPA dilation was defined as Z-score (standard deviation units from the mean) >2 24 . AAO dilation and stenosis were regarded as Z-score > 2 and Z-score < −2, respectively 25 .