Assessment of Intracardiac and Extracardiac Anomalies in Patients with Various Types of Pulmonary Atresia by Low-dose Dual-source Computed Tomography


 Background: pulmonary atresia (PA) is a group of heterogeneous complex congenital heart disease which need more than one study modality to get correct diagnoses. This study aims to investigate the diagnostic power of low-dose dual-source computed tomography (DSCT) for all intracardiac and extracardiac anomalies in patients with PA compared with transthoracic echocardiography (TTE).Materials and methods: This retrospective study enrolled 73 patients and divided them into three groups according to their main diagnosis. All associated malformation and clinical information, including treatments, were recorded and compared among the three groups. The diagnostic power of DSCT and TTE on all associated anomalies were compared. The surgical index (McGoon ratio, pulmonary arterials index (PAI), and total neopulmonary arterial index) and radiation dose were calculated on the basis of DSCT.Results: Of the patients, 29, 29, and 15 were divide into the groups of PA with ventricular septal defect (VSD), PA with VSD and major aortopulmonary collateral arteries, and PA with other major malformations, respectively. Consequently, 178, 144, and 12 intracardiac, extracardiac, and other major anomalies were diagnosed, respectively. Moreover, DSCT showed a better diagnostic performance in extracardiac anomalies (137 vs 100, p = 0.000), whereas TTE could diagnose intracardiac anomalies better (158 vs 134, p = 0.001). The McGoon ratio, PAI, and treatment methods were significantly different among the three groups (p = 0.027, p = 0.035, and p = 0.041, respectively).Conclusion: More than one imaging modality should be used to make a correct diagnosis when clinically suspecting PA. DSCT is superior to TTE in diagnosing extracardiac anomalies and could be used to roughly calculate surgical indices to optimize treatment strategy.


Introduction
Pulmonary atresia (PA) is identi ed as a group of heterogeneous congenital heart disease (CHD) whose most important feature is the lack of continuity between the pulmonary arteries and the ventricle. Hence, PA is nearly accompanied by other congenital intracardiac and extracardiac abnormalities (1)(2)(3). PA is rare but fatal (4). The survival rate is low without early interventions. Early and late mortality is high in all types of PA (5). In fact, even patients underwent operation, the success rate of surgery is low during the rst 30 years after this disease being reported (6, 7)However, because of the histologic study of major aortopulmonary collateral arteries (MAPCAs), native pulmonary arteries (NPA), and accumulated knowledge of the blood supply of the lungs (8, 9), the survival rate is gradually increasing (10,11). Thus, the condition of NPA, MAPCAs, as well as other anomalies are of the highest importance for surgical strategy and management (6, 12).
Transthoracic echocardiography (TTE) is a rst-line CHD examination, which could investigate intracardiac anomalies well. However, TTE is not very useful for extracardiac anomalies that are crucial for surgical choices. Cardiac computed tomography is an excellent imaging modality in patients with Page 3/20 CHD, which could reliably visualize pulmonary arterial supply (13,14). Additionally, dual-source computed tomography (DSCT) broadens its application range because of its lower radiation dose and higher density and spatial resolution (15). However, only a few studies explored the value of DSCT for diagnosing PA focusing only on PA with ventricular septal defect (VSD) and MAPCAs (16,17). PA is not just one type. Hence, this study was divided PA into three groups according to their main diagnosis. Furthermore, the three groups were compared, the DSCT diagnostic power for all intracardiac and extracardiac deformities in PA was analyzed, and the power with TTE was compared.

Study population
This study retrospectively enrolled 73 PA patients with various deformations who underwent preoperative DSCT and TTE examinations from June 2012 to December 2020 at the medical center of this study. The inclusion criteria were (1) patients who underwent surgery or cardiovascular angiography (CA) with PA included as the nal diagnoses and (2)  was from the inlet of the thorax to 2 cm below the diaphragm level. A nonionic contrast agent (iopamidol, 370 mg/mL; Bracco, Italy) was given intravenously (1.5 mL/kg body weight) at a rate of 1.2-2.5 mL/s, followed by 20 mL of saline solution. Automated bolus-tracking software was utilized to start the scan when the region of interest attenuation threshold reached 100 HU following a delay of 5 s. The protocol parameters ( ash chest pain electrocardiogram; ECG) were as follow: tube voltage (80−120 kV; controlled by CARE KV), CARE Dose 4D (used to reduce the tube current), gantry rotation time (0.28 s), and pitch (0.2-0.5; adapted to heart rate). Moreover, the eld of view was adjusted to body size.
Images were reconstructed with a slice thickness and an increment of 0.75 and 0.5 mm, respectively. The convolution kernel was I26f medium smooth ASA. Sinogram-a rmed iterative reconstruction (strength, 3) and a retrospective ECG-gated technique were used to improve image quality. All image data were transferred to a workstation (Syngo; Siemens Medical Systems, Forchheim, Germany). Several postprocessing methods (e.g., multiplanar reformations, volume rendering, and maximum intensity projection) were applied to complete image analysis (16).

Image analysis
All DSCT images were retrospectively reviewed by two veteran radiologists without knowing the surgery or DSA results. The main abnormalities were carefully reviewed at the workstation using different postprocessing methods. The diameters of the left pulmonary arterials, right pulmonary arterials, MACAPs, and descending aorta were recorded similarly to that in reference (16). The only difference in the measurement was that the main pulmonary arterial (MPA) if existing was located at the maximum of MPA. All measurements avoided narrow places. The body surface area was calculated by the Stevenson formula. The McGoon ratio, pulmonary arterials index (PAI), and total neopulmonary arterial index (TNPAI) were calculated in the standard ways.
The echocardiographic images were performed by an experienced cardiac ultrasound radiologist and checked by another senior radiologist. All detected malformations were recorded from long and short cardiac axis view at the xiphoid process, parasternum, and suprasternal fossa. The aortopulmonary window level was used to detect the collateral circulation.

Radiation dose estimation
DSCT examinations strictly adhered to the principle of "as low as reasonably achievable". Tube voltage, tube current, and pitch were adjusted on the basis of every patient's individual circumstance to lower the dose as much as possible as illustrated above. Volume CT dose index (CTDI vol ) and dose length product

Basic characteristics and surgical indices among three subgroups
Of the patients, 29, 29, and 15 were divided into the groups of PA/VSD/MAPCAs ( Fig. 1-3), PA/VSD (Fig. 4), and the PA group with other major malformations (i.e., six patients with a double outlet of the right ventricle, two patients with SV, two patients with SV and SA, one patient with SV and mitral valve atresia, and three patients with intact ventricle (Fig. 5)), respectively. For basic clinical characteristics, most indices showed no signi cant difference except for age and respiratory rate. For quantitative parameters that are of guiding signi cance for surgical options, McGoon ratio and PAI were signi cantly different among the three groups (p = 0.027 and p = 0.035, respectively). However, McGoon and TNPAI showed no signi cant difference between PA/VSD/MAPCAs and PA patients with other major malformations. Table 1 shows more detailed information regarding the three groups. Of the patients, 36 and 29 underwent or prepared to undergo multiple-stage surgeries and one-stage surgery (Fig. 6), respectively, and eight were inoperable after DSA examination. The quantitative parameters were not signi cant among the different treatments group ( Table 2). All ICC scores were > 0.75, showing great repeatability (Table 3).

Radiation dose estimation
The DLP and CTDI vol of the different groups are classi ed by age (

Discussion
PA is a complex CHD accompanied by different intracardiac or extracardiac anomalies. The treatments are diverse in different anomalies (11,12). Hence, an accurate preoperative diagnosis is of great importance for patient treatment and management. This study has major discoveries. (1) Different groups of PA patients have different surgical indices (McGoon ratio, PAI, and TNPAI) and DSCT can demonstrate NPA and MAPCAs well. Therefore, the surgical indices could be roughly calculated to design treatments. (2) DSCT has a better diagnostic performance for extracardiac anomalies than that of TTE.
Patients in this study were classi ed into three groups according to their major anomalies. Most studies only focused on one type of PA, that is, PA/VSD, PA/VSD/MAPCAs, or PA/IVS (20). and it is believed that no study comparing different types of PA currently exists. Additionally, only a few studies showed the values of low dose DSCT in patients with PA. The results of this study showed that the common clinical data were not signi cantly different except for age and respiratory rate. However, all these data indicated that patients were in a poor situation. For example, preoperative SpO 2 is low and symptoms are obvious and critical. This may be explained by the fact that PA is a complex and severe CHD which makes them in poor situation. Meanwhile, most patients in the three groups were able to undergo surgical treatments meaning that they were in the same poor situation to some extent. By contrast, the surgical indices (McGoon ratio and PAI), as well as various treatments among the three groups, was signi cantly different.
PA/VSD had a higher McGoon ratio and PAI. Moreover, all patients underwent surgical treatments. The other two groups had a lower McGoon ratio and PAI. Consequently, more patients only underwent DSA examinations or palliative surgery. Different McGoon ratios and PAI indicate the development of the NPA situation. A higher ratio means a lower risk of surgery and better outcome (21,22). Thus, patients with low surgical indices could not undergo the one-stage surgery, which helps to explain the fact that more patients in the two latter groups did not undergo one-stage surgery in this study. However, TNPAI was not signi cant in the latter two groups, which may be because of the small sample size (only six patients had MAPCAs in the group of PA with other major malformation). DSCT could depict NPA and MAPCAs well and display them in three dimensions with the help of postprocessing techniques. Thus, their diameter could be roughly measured. On the basis of this fact, surgical plan could be roughly designed. Moreover, DSCT could show the stenosis places and the concrete origin locations of MAPCAs which are important for the surgical plan of patients with PA/VSD/MAPCAs. This study demonstrates the value of DSCT used to design the treatment plans without undergoing DSA. DSA can be used to assess the situation of NPA, MAPACs and the pulmonary blood supply (23). But it is invasive and expensive. What's more, DSA with the highest patient radiation dose has an insurmountable defect for infants and children because they are more vulnerable to radiation (24).
Compared with echocardiography, DSCT demonstrates extracardiac anomalies better, while TTE diagnoses intracardiac anomalies (especially valve anomalies) better in this study, which is consistent with the previous studies (25,26). Complex congenital heart diseases often accompanied by not only intracardiac malformation but also extracardiac malformation which need more than one imaging modalities to get a correct diagnosis. TTE is the routine examination for heart diseases, especially for CHD, which could investigate the intracardiac anomalies and hemodynamics well. However, TTE is not very useful for extracardiac anomalies for its limited acoustic window and is dependent on the operators heavily (27). DSA is identi ed as "gold standard" for the blood supply of the lungs. But it also has some shortcomings as illustrated above. Cardiac MRI can measure hemodynamics, either. But it is not often applied to CHD for it is demanding for motionlessness and time which is di cult for young patients and patients with CHD. Besides, cardiac MRI also has little contribution to pulmonary artery measurement (28).
All of these insu ciencies can be complemental by DSCT. With the development of DSCT, it has increasingly been applied to CHD. It can portray the extra-cardiac anomalies well and provide more mediastinal anatomy information for surgeon to design surgical plans before the operation owing to its high density resolution and powerful postprocessing techniques. Moreover, its high temporal resolution enables its use in patients with high heart rate (29) by using two independent X-ray tubes and corresponding detectors. Additionally, as our results shows, its radiation dose has been reduced to as low as reasonably achievable (14), which makes it suitable for young patients. Thus, DSCT plays an irreplaceable role in the diagnosis of PA and treatment and management design.
Several limitations exist in this study. First, all patients came from a single center, which leads to selection bias and a relatively small sample size, especially for the group of PA with other major malformation, which in uenced the data collection and analysis of this study. Hence, further studies with larger samples coming from multicenter should be conducted. Second, the radiation dose has reduced greatly, although still existing, which helps reduce the injury for young patients, with the help of technique development. Third, the outcomes of the different groups with long-term follow-up, which may aid in further management of this disease, were not tracked.

Conclusion
PA is a rare and fatal type of heterogeneous CHD. More than one imaging modality should be used to make a correct diagnosis when clinically suspecting PA. TTE can diagnose intracardiac anomalies well, whereas DSCT can demonstrate extracardiac malformation better and give more information to optimize the surgical design.

Funding
This study has received funding by 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18013) and Sichuan Science and Technology Program (2020YJ0229). The funding sources had no role of the study design; collection; analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Con icts of interest/Competing interests
The authors declare that they have no con ict of interest.

Availability of data and material
All data and material used in this study are included in this manuscript.
Authors' contributions QWL participated in the study design, data collection, performed the statistical analysis, and drafted the manuscript. YZG contributed to study design, and contributed to preparation, editing and review of the manuscript. ZXZ participated in the study design, data collection, and contributed to quality control of data and analysis, and editing and review of the manuscript. SK and JL contribute to preparation of the manuscript. SLT participated in data acquisition and analysis. All authors read and approved the nal manuscript.
Ethics approval   Two sets of images of a PA/VSD/ MAPCAs patients Images of a-c were captured in 2013 and d-f were taken in 2019. Unlike with the patient in gure 1, the blood supply of this patient lungs depended more on right CA (red arrows) than MAPCA (blue arrows). After six years, the right CA dilated more distinct, while the left/ right pulmonary artery (yellow arrows) and MAPCA changed little.  The images of a PA patient with intact ventricular septum (IVS) complicated by right ventricular dependent coronary circulation (RVDCC) PA/IVS/RVDCC is a rare and fatal type of PA whose treatments