Skip to main content

Multi-detector computed tomography (MDCT) as a diagnostic tool in assessment of thoracic aortic anomalies in pediatric patients

Abstract

Background

A wide variety of congenital thoracic aortic variants and pathological anomalies could be assessed recently in diagnostic and interventional radiology. Multi-detector computed tomography (MDCT) is one of the most important non-invasive diagnostic tools for their detection. The aim of the study was to evaluate role of MDCT scanning for diagnosis of thoracic aortic anatomic variants and diseases in pediatric patients.

Results

Thirty patients (15 male and 15 female), mean age (8.49 ± 20.29 months) were diagnosed with different thoracic aortic anomalies by MDCT then confirmed by surgical results. MDCT was more sensitive than echocardiography in detection of hypo plastic arch, vascular rings, interrupted aortic arch anomalies, and aortic coarctation. Both MDCT and echocardiography showed 100% sensitivity in their detection of TGA, TOF, and PDA. MDCT detected 6 cases of right-sided aortic arch while echo missed 2 cases. Different aortic arch branching patterns and coronary origin were better demonstrated by MDCT.

Conclusion

320-Multi-detector computed tomography is a reliable tool for optimal detection of thoracic aortic anomalies and preoperative planning.

Background

Development of the aorta takes place during the third week of gestation. It is a complex process that can lead to a variety of congenital variants and pathological anomalies [1].

Thoracic aortic anomalies can be divided into aortic root, aortic arch, and descending aortic anomalies [2].

Echocardiography remains the first option for patients with clinical diagnosis of congenital heart disease due its excellent anatomic and functional assessment capabilities; however, it is not precise in delineation of great arteries and coronary arteries [3].

For many years, invasive angiographic techniques were considered gold standard for the assessment of thoracic aortic abnormalities. However, the complexities and complications inherent to invasive imaging have meant that more recently non-invasive techniques such as multi-detector CT (MDCT) have been increasingly used in congenital cardiovascular disorders [4].

MDCT has emerged as a fundamental tool for the diagnosis and pre-surgical work-up of thoracic aortic abnormalities due to its high spatial resolution, large area of coverage, short scan time, multi-planar reformatting, and 3D volume rendering. It is now one of the most widely used modalities for the detection of congenital abnormalities of the thoracic aorta [5].

The aim of this prospective study was to assess the role of multi-detector CT (MDCT) as a diagnostic and preoperative imaging modality for thoracic aortic anomalies and its variants.

Methods

Study design and population

The current prospective study included a group of 30 patients (15 male and 15 female) with echocardiographic diagnosis of thoracic aortic anomalies.

The study included any referred patient with echocardiographic diagnosis of thoracic aortic anomaly with no sex predilection; pediatric age group was included. Excluded cases were patients with known history of allergy to contrast media and patients with impaired renal function tests. Study duration was 1 year.

Preparation and protocol

All the studied patients included in the study were subjected to full history taking from their guardians, clinical examination, including vital signs monitoring before, during, and after CT examination. Renal function tests and echocardiography were checked before scanning.

Cardiac multi detector computed tomography examination

All patients were examined by 320-multidetector CT scanner (Aquilion One; Toshiba medical systems, Ohtawara, Jaban); it provided 160 mm of coverage in the z direction as the detector element consists of 320 × 0.5 mm detector. As the gantry rotation was 0.35 s, we could image the heart in a single heartbeat, and this provided excellent anatomic imaging of the whole heart, its great vessels, and coronaries.

Preparation

The procedure was described to parents for reassurance; suitable IV cannula was inserted (20 to 24 gauge) in lower limb veins (17 cases) and right upper limb veins in (13 cases) then ECG skin patches for ECG electrodes application. Sedation was done for those who were uncooperative orally with chloral hydrate (50–100 mg/kg; maximum dose, 2000 mg). Verbal instructions of breath holding were successful with one patient.

Contrast injection

All the patients were injected with non-ionic contrast medium (Ultravist 300, Schering AG, Germany or Omnipaque 300, Nycomed, Amersham); this was injected in 29 and 1 patients respectively in a dose 2 ml/kg through the peripherally inserted IV cannula using dual syringe mechanical power injector (Stellant D, Medrad, Indianola, PA, USA) with flow rate 1–1.5 ml/s increased to 3 ml/s in older children followed by saline flushing. The scanning delay was determined by a bolus tracking technique.

Manual bolus tracking was applied after 10 to 15 s from contrast material injection timing (for upper limb venous line) and after 20 s (for lower limb venous line), the scan is initiated after both ventricles opacification.

Monitor andemergency set

  • Pediatric sphygmomanometer, oxygen container with mask and extension tubing, and emergency drugs like dexamethasone for contrast allergy.

  • Facility to transfer the patient to the emergency room if uncontrolled complication developed.

Data acquisition

The patient lay on the CT table in supine position.

  • A scanogram was obtained.

  • Scan range: from the root of the neck, including the proximal aspects of the common carotid and subclavian arteries down to the level of the portal vein inferiorly. This range was important to detect associated aortic arch branch anomalies, cardiac situs, abdominal aortic coarctation, and infra-diaphragmatic type of total anomalous pulmonary venous drainage.

  • Scan parameters: the patients were scanned using a single phase retrospective ECG gated CTA volume scan with a rotation time of 0.35 s and a tube voltage of 80 kV increased to 100 kV in two older children. The tube current was automatically adjusted based on the size and shape of the individual patient.

Post processing

Full volumes were reconstructed in 0.5 mm-thickness slice. Post-processing of (MDCT) scans was performed on a dedicated Vital Images work station.

Maximum intensity projections (MIP), three-dimensional volume rendering (VR), multiplanar (MPR), and curved planer reformations (CPR) were used to display thoracic aortic variants and malformations.

Image interpretation

Images were independently analyzed by two different radiologists both were aware of the clinical data and echocardiographic results. Finally, correlation with the operational data was done.

Standard reference

The final diagnosis was reached by comparing the imaging findings with the operative data or cardiac catheterization which were the gold standard for the diagnosis.

Statistical analysis

Data were fed to the computer and analyzed using IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. The Kolmogorov-Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, and standard deviation. Significance of the obtained results was judged at the 5% level.

Results

This study enrolled 30 patients (15 males and 15 females) with 48 thoracic aortic abnormalities, with male to female ratio (1:1). Age of the patients ranged from 2 days to 9 years.

Clinical presentations of the patients were poor feeding, dyspnea, cyanosis, congestive heart failure, failure to thrive, and recurrent chest infections.

The thoracic aortic abnormalities detected on MDCT were correlated with the diagnostic ability and the degree of certainty of echocardiography as routine evaluation technique. Both imaging modalities results were compared to either surgical intervention or conventional catheter results as a gold standard reference.

The thoracic aortic abnormalities encountered in this study by MDCT included aortic coarctation (n = 11; 36.7%), hypoplastic aortic arch (n = 7; 23.3%), overriding aortic root (n = 5; 16.7%), patent ductus arteriosus (PDA) either isolated or associated with other anomalies (n = 14; 43.3%), two of them were isolated PDA with no intra cardiac or another thoracic vascular anomaly, truncus arteriosus (n = 3; 10%), supra-valvular stenosis with sub-aortic membrane (n = 2; 6.2%), vascular ring (n = 2; 6.2%), interrupted arch (n = 2; 6.2%), small aortic root (n = 1; 3.3%), and hypoplastic ascending aorta (n = 1; 3.3) (Fig. 1).

Fig. 1
figure 1

Percentage of thoracic aortic anomalies detected by MDCT

Echocardiography missed one aortic interruption case, one vascular ring case, and two cases of arch hypoplasia which were detected by MDCT and confirmed by aortic angiography.

MDCT missed one case of arch hypoplasia which was detected by conventional catheter.

Both echocardiography and MDCT detected correctly all cases of transposition of great arteries (TGA), truncus arteriosus, overriding aortic root, small aortic root, patent ductus arteriosus, and supra-valvular stenosis with sub-aortic membrane (Tables 1 and 2).

Table 1 Thoracic aortic anomaly diagnosed by Echo, MDCT, and intervention/catheter
Table 2 Agreement (sensitivity, specificity, and accuracy) for Echo compared to surgery/catheter angiography

In this study, MDCT detected 6 cases of right-sided aortic arch confirmed by conventional catheter with 100% sensitivity, while echocardiography detected 4 case of right-sided arch missing 2 cases with 60% sensitivity.

The site, degree, and the length of the coarctation were reliably described by multi-planar and three dimensional MDCT angiography images (Table 3).

Table 3 Coarctation features detected by MDCT

In this study, truncus arteriosus type IV represented 66.6% of truncus arteriosus cases. All cases with aortic interruption were of type B.

Normal arch branching pattern was described in 60% of cases followed by right-sided aortic arch with mirror image branching pattern in 16.7% of cases (Table 4).

Table 4 Frequency of aortic arch branching pattern detected by MDCT (n = 30)

The association between aortic arch branching patterns and different aortic anomalies detected by MDCT was tabulated and showed that abnormal branching patters were more frequent in cyanotic anomalies (Table 5).

Table 5 Aortic arch branching patterns association with different thoracic aortic anomalies by MDCT

In this study, 73.3% of patients had normal origin of coronaries confirmed by conventional catheter; MDCT failed to detect coronaries origin in 10% of cases (Fig. 2).

Fig. 2
figure 2

Coronary anomalies detected by MDCT (n = 30)

Discussion

Multi-detector computed tomography and spiral CT are widely used in diagnosis of thoracic aortic diseases. A CT scan is simple, non-invasive, and quick. Contrast administration adds more information about cardiovascular system and extra-cardiac vasculature and thoracic structures like tracheal and esophageal abnormalities [4, 6].

In the current study, all patients were sedated by chloral hydrate (50–100 mg/kg; maximum dose, 2000 mg) apart from one case aged 9 years who responded well to verbal instructions. No sedation-related complications were encountered in the study. This was the same as Kimura-Hayama et al. [7] (Figs. 34, and 5).

Fig. 3
figure 3

A case of interrupted aortic arch type B aged 2 days presented with failure to thrive. a Volume rendered image of the heart and great vessels with interruption of aortic arch distal to left common carotid artery, descending aorta arising from a small PDA connecting it to main pulmonary trunk with focal coarctation at ductal site. b Volume rendered image of thoracic aorta with type B interruption. c Sagittal MIP image showing length of interrupted segment of aortic arch. d Axial MIP image showing length of interrupted segment of aortic arch

Fig. 4
figure 4

A case of left hypo plastic heart syndrome with aortic arch hypoplasia aged 9 days presented with failure to thrive. a Volume rendered image of the thoracic aorta and left ventricle showing mild supravalvular stenosis of the aortic root which arises from hypoplastic left ventricle also aortic arch hypoplasia. b Volume rendered image of the heart and great vessels showing a large PDA connecting aorta to pulmonary artery, left ventricular hypoplasia and right ventricular hypertrophy. c LVOT view showing hypoplastic left ventricle with aortic valve thickening with mild supravalvular aortic stenosis. d Two chamber view of the left side of heart showing small mitral annulus

Fig. 5
figure 5

A case of double aortic arch aged 9 months presented with dyspnea. a 2D MIP coronal image showing complete vascular ring formation by two aortic arches with the previously described branching pattern. b Volume rendered superior view of the heart and great vessels showing double aortic arches with right side predominance forming a complete vascular ring. c, d Tracheal narrowing at site of vascular ring shown in volume rendered image of the trachea (c) and in coronal MinIP image (d)

Cases with aortic coarctation were correctly described as regards coarctation segment length, location, extend of stenosis, and extent of collaterals formation using axial, sagittal oblique MIP, volume-rendered images. Percentage of stenosis was calculated but it is not useful for visualizing the aortic gradient which agreed with Chen et al. [8] Türkvatan et al. [9], and Al-Azzazy et al. [10].

In this study, the length of the coarctation was short in 9 cases (81.8%) and long in 2 cases (18.8%). The length of the coarctation was considered short if the length of the narrowed aortic segment was less than 5 mm and long if the length of the narrowed aortic segment was more than 5 mm. These percentages are nearly the same as Türkvatan et al. [9], and slightly less than that of Al-Azzazy et al. [10] and Ahmed et al. [11] who had a higher percentage for short segment coarctation patients.

As regards vascular rings detected, Echo and MDCT had 50% and 100% sensitivity respectively for detection of vascular rings when compared to conventional angiography. The detected types of vascular rings were double aortic arch with right arch predominance and right side aortic arch with aberrant left subclavian which was consistent with Hamisa et al. [12] who concluded that double aortic arch and right side aortic arch with aberrant left subclavian were the commonest forms of vascular rings in their study with 100% sensitivity for MDCT in vascular rings detection.

Interrupted aortic arch (IAA) type B was the final diagnosis of two cases in this study with percentage of 6.6% which is close to percentage described by Chen et al. [8] who detected IAA percentage of 8.8% and El Dien et al. [13] who detected the same percentage of IAA type B among his cases. MDCT had 100% sensitivity for interrupted arch detection; echocardiography showed 50% sensitivity when compared to conventional angiography results.

Jia et al. [14] confirmed the importance of MDCT in detection of major aorto-pulmonary collaterals (MAPCAs) as they found that MDCT has the potential to replace preoperative catheterization as they found excellent anatomy agreement between MDCT and surgery.

In the current study, echocardiography missed detection of one case with MAPCAs which was correctly detected by MDCT and conventional angiography; this agreed with Nakhla et al. [15] who described lower echocardiography sensitivity for MAPCAs detection.

In this study, different aortic arch sidedness and branching patterns were described and their presence in association with different thoracic aortic pathologies was assessed using MDCT as a preoperative planning tool and was found that:

  • Left-sided aortic arch with aberrant right subclavian artery had a higher incidence in females (2 cases, 13.3%) than males (1 case, 6.7%) which is similar to Piyavisetpat et al. [16] and Karacan et al. [17].

  • Sixty percent of cases showed the normal branching pattern of left sided aortic arch which agreed with Zhivadinovik et al. [18].

  • Left-sided aortic arch with aberrant right subclavian artery came as the third common branching pattern detected by MDCT which agreed with Celikyay et al. [19]. It was the commonest anomalous form of left-sided aortic arch detected in our study which was the same result found by Raimundo et al. [20].

  • Left-sided aortic arch with bovine branching pattern came as the fourth common detected aortic arch branching pattern with a percentage of 6% of cases which was close to the percentage detected by Müller et al. [21]. It was lower than the percentage detected by Jakanani et al. [22] which was 20% of their cases.

  • One case of aortic coarctation was associated with left-sided aortic arch with bovine branching pattern. The presence of this anomaly with aortic coarctation cases required the use of median sternotomy instead of lateral thoracotomy during surgical repair, which was an added preoperative planning value for MDCT.

  • Left-sided aortic arch with aberrant right subclavian artery (ARSA) and right-sided arch with mirror image branching pattern were associated with cases of tetralogy of Fallot (TOF), TGA, and truncus arteriosus which agreed with Tawfik et al. [23] and Turkvatan et al. [9].

The coronary artery anatomy is important for surgical planning of complete TGA. Surgical correction of TOF requires right ventriculotomy to relieve right ventricular outflow tract (RVOT) obstruction. Hence, any major coronary artery crossing the RVOT can be accidentally damaged during surgical repair [24].

In this study, cases with TGA and truncus arteriosus had higher prevalence of coronary anomalies compared to other cases of aortic anomalies which agreed with Yu et al. [24].

This study showed that MDCT has a high diagnostic sensitivity of thoracic aortic anomalies reaching up to 100% in different variables, with the advantage of giving precise anatomical details and volume rendered images which are very helpful before surgery for accurate surgery planning.

Both Echo and MDCT had 100% sensitivity in detection of aortic root anomalies. MDCT showed higher sensitivity in detection of aortic arch and descending aortic anomalies (MDCT 100%, Echo 91.4%). Echo was a better diagnostic tool in evaluation of aortic valve anatomy as motion artifact was a drawback in three cases that could not be evaluated by MDCT.

We acknowledge that the only limitation was the retrospective ECG gating thus relatively increase the radiation dose in infants and children.

Conclusion

320-Multi-detector computed tomography is a reliable tool for optimal detection of thoracic aortic anomalies and preoperative planning.

Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

Abbreviations

ARSA:

Aberrant right subclavian artery

IAA:

Interrupted aortic arch

MAPCS:

Major aortopulmonary collaterals

PDA:

Patent ductus arteriosus

TOF:

Tetralogy of Fallot

TGA:

Transposition of great arteries

VR:

Volume rendered

MDCT:

Multi-detector computed tomography

MIP:

Minimum intensity projection

MiniP:

Minimum intensity projection

LSCA:

Left subclavian artery

LVOT:

Left ventricular out flow

2D:

Two dimensions

References

  1. Ilina M, Lilley S (2019) Embryology of the great vessels. In: Carachi R, Doss S (eds) Clinical Embryology, Clinical Embryology. Springer, Cham

    Google Scholar 

  2. Lindsay AC, Sriharan M, Lazoura O, Padley SP, Nicol ED, Rubens MB (2014) Multidetector computed tomography of congenital aortic abnormalities. Int J Cardiol 172:537–547

    Article  Google Scholar 

  3. Evangelista A, Flachskampf FA, Erbel R, Antonini-Canterin F, Vlachopoulos C, Rocchi G, Sicari R, Nihoyannopoulos P, Zamorano J (2010) Echocardiography in aortic diseases: EAE recommendations for clinical practice. Eur J Echocardiogr 11:645–658

    Article  Google Scholar 

  4. Hassanien OA, El-Shafey KI, Khedr RA, Elsheikh RG (2018) Role of 320-MDCT in assessment of cardiac great arteries anomalies. Egypt J Radiolo Nuc Med 49:993–1002

    Article  Google Scholar 

  5. Lindsay AC, Nair A, Rubens MB (2019) Multidetector computed tomography of the aorta. In: Olaf HS, John RP, Lars GS (eds) Surgical Management of Aortic Pathology, 1st edn. Springer, Vienna

    Google Scholar 

  6. Chung JH, Ghoshhajra BB, Rojas CA, Dave BR, Abbara S (2010) CT angiography of the thoracic aorta. Radiol Clin 48:249–264

    Article  Google Scholar 

  7. Kimura-Hayama ET, Meléndez G, Mendizábal AL, Meave-González A, Zambrana GF, Corona-Villalobos CP (2010) Uncommon congenital and acquired aortic diseases: role of multidetector CT angiography. Radiographics 30:79–98

    Article  Google Scholar 

  8. Chen X, Qu YJ, Peng ZY, Lu JG, Ma XJ (2013) Diagnosis of congenital aortic arch anomalies in Chinese children by multi-detector computed tomography angiography. Med Scie 33:447–451

    Google Scholar 

  9. Türkvatan A, Büyükbayraktar FG, Olçer T, Cumhur T (2009) Congenital anomalies of the aortic arch: evaluation with the use of multidetector computed tomography. Korean J Radiol 10:176–184

    Article  Google Scholar 

  10. Al-Azzazy MZ, Nasr MS, Shoura MA (2014) Multidetector computed tomography (MDCT) angiography of thoracic aortic coarctation in pediatric patients: pre-operative evaluation. Egypt J Radiolo Nuc Med 45:159–167

    Article  Google Scholar 

  11. Ahmed KO, Mousa MA (2011) Role of multidetector computed tomography (MDCT) angiography in preoperative assessment of coarctation of the aorta in pediatric patients and young adults. Egypt J Radiolo Nuc Med. 42:297–303

    Article  Google Scholar 

  12. Hamisa M, Elsharawy F, Elsherbeny W, Bayoumy S (2018) Comparative study between multi-detector computed tomography and echocardiography in evaluation of congenital vascular rings. Alex J Med. 54:717–723

    Article  Google Scholar 

  13. El Dien HS, Ibrahim LA, Hashem RH (2014) Evaluation of aortic arch anomalies by echocardiography and CT angiography, could CT be the primary method of diagnosis? J Adv Med Med Res 4(16):3179–3195

  14. Jia Q, Cen J, Li J, Zhuang J, Liu H, Zhang Q, Liu X, Huang M, Liang C (2018) Anatomy of the retro-oesophageal major aortopulmonary collateral arteries in patients with pulmonary atresia with ventricular septal defect: results from preoperative CTA. Eur Radiol. 28:3066–3074

    Article  Google Scholar 

  15. Nakhla OL (2015) Role of multi-slice CT angiography in the evaluati of conotruncal anomalies. Egypt J Radiolo Nuc Med. 46:371–377

    Article  Google Scholar 

  16. Piyavisetpat N, Thaksinawisut P, Tumkosit M (2011) Aortic arch branches’ variations detected on chest CT. Asian Biomed 5:817–824

    Google Scholar 

  17. Karacan A, Türkvatan A, Karacan K (2014) Anatomical variations of aortic arch branching: evaluation with computed tomographic angiography. Cardiol Young. 24:485–493

    Article  Google Scholar 

  18. Zhivadinovikj J, Matveeva N, Zafirova B, Dodevski A, Petrovska T (2018) Anatomical variations of the aortic arch. JMS 1:20–24

    Google Scholar 

  19. Celikyay ZR, Koner AE, Celikyay F, Denız C, Acu B, Firat MM (2013) Frequency and imaging findings of variations in human aortic arch anatomy based on multidetector computed tomography data. Clin Imaging. 37:1011–1019

    Article  Google Scholar 

  20. Raimundo E, dos Santos GM, Pereira M, Farias L, Pedri AF, de Sales TS, Ferreira RHQ (2019) (2019) Anomalies and anatomical variants of the aortic arch and origin of the neck vessels. In: European Congress of Radiology

    Google Scholar 

  21. Müller M, Schmitz BL, Pauls S, Schick M, Röhrer S, Kapapa T, Schlötzer W (2011) Variations of the aortic arch—a study on the most common branching patterns. Acta Radiol. 52:738–742

    Article  Google Scholar 

  22. Jakanani GC, Adair W (2010) Frequency of variations in aortic arch anatomy depicted on multidetector CT. Clin Radiol. 65:481–487

    Article  CAS  Google Scholar 

  23. Tawfik AM, Sobh DM, Ashamallah GA, Batouty NM (2019) Prevalence and Types of Aortic Arch Variants and Anomalies in Congenital Heart Diseases. Acad Radiol. 26:930–936

    Article  Google Scholar 

  24. Yu FF, Lu B, Gao Y, Hou ZH, Schoepf UJ, Spearman JV, Cao HL, Sun ML, Jiang SL (2013) Congenital anomalies of coronary arteries in complex congenital heart disease: diagnosis and analysis with dual-source CT. J Cardiovasc Comput Tomogr. 7:383–390

    Article  Google Scholar 

Download references

Acknowledgement

Not applicable.

Funding

Not applicable.

Author information

Authors and Affiliations

Authors

Contributions

AYS have the idea of research, follow up cases, writing, publishing, and analysis the data. KIE have the final revision and supervision. OAH refer the cases and adjust any clinical problem and feedback of patients. RMD meticulous aid in writing. All authors read and approve the final manuscript.

Corresponding author

Correspondence to Dawlat Nader Eltatawy.

Ethics declarations

Ethics approval and consent to participate

This study was conducted according to the guidelines of the ethics committee of Tanta University and was approved by our institutional review board. All patients gave written informed consent to be imaged in our study. Ethics committee’s reference number (39793-12-18).

Consent for publication

All patients included in this research gave written informed consent to publish the data contained within this study.

Competing interests

The authors declare that there is no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eltatawy, D.N., Elsharawy, F.A., Elbarbary, A.A. et al. Multi-detector computed tomography (MDCT) as a diagnostic tool in assessment of thoracic aortic anomalies in pediatric patients. Egypt J Radiol Nucl Med 52, 39 (2021). https://doi.org/10.1186/s43055-020-00399-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s43055-020-00399-5

Keyword