Establishment of a database of fetal congenital heart ... - Core

Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 284e289

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Original Article

Establishment of a database of fetal congenital heart malformations and preliminary investigation of its clinical application Jun-Xue Gao, Qiu-Yan Pei*, Yun-tao Li, Zhen-Juan Yang Ultrasound Department, Peking University People's Hospital, Beijing, China

a r t i c l e i n f o

a b s t r a c t

Article history: Accepted 27 January 2015

Objective: The aim of this study was to create a database of anatomical ultrathin cross-sectional images of fetal hearts with different congenital heart diseases (CHDs) and preliminarily to investigate its clinical application. Materials and methods: Forty Chinese fetal heart samples from induced labor due to different CHDs were cut transversely at 60-mm thickness. All thoracic organs were removed from the thoracic cavity after formalin fixation, embedded in optimum cutting temperature compound, and then frozen at 25 C for 2 hours. Subsequently, macro shots of the frozen serial sections were obtained using a digital camera in order to build a database of anatomical ultrathin cross-sectional images. Results: Images in the database clearly displayed the fetal heart structures. After importing the images into three-dimensional software, the following functions could be realized: (1) based on the original database of transverse sections, databases of sagittal and coronal sections could be constructed; and (2) the original and constructed databases could be displayed continuously and dynamically, and rotated in arbitrary angles. They could also be displayed synchronically. The aforementioned functions of the database allowed for the retrieval of images and three-dimensional anatomy characteristics of the different fetal CHDs, and virtualization of fetal echocardiography findings. Conclusion: A database of 40 different cross-sectional fetal CHDs was established. An extensive database library of fetal CHDs, from which sonographers and students can study the anatomical features of fetal CHDs and virtualize fetal echocardiography findings via either centralized training or distance education, can be established in the future by accumulating further cases. Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.

Keywords: anatomic section congenital heart disease database fetal

Introduction Fetal congenital heart disease (CHD) is the leading cause of infant death [1e3]. For pregnant women, an antenatal diagnosis of seriously complicated CHD can not only reduce the birth rate but also improve the success rate of surgery after birth, with the help of prenatal counseling [4e6]. Fetal echocardiography (FECG) is the main method of prenatal diagnosis of CHD. However, due to the effects of an unstable fetal position, rapid heart rate, subtle heart structures, and special fetal circulations (intrauterine blood flow properties in the foramen ovale and ductus arteriosus), as well as

* Corresponding author. Department of Obstetrics and Gynecology, Peking University People's Hospital, Number 11 Xizhimen South Street, Beijing 100044, China. E-mail address: [email protected] (Q.-Y. Pei).

other limitations, FECG is more difficult to perform than adult echocardiography. Consequently, the technology is still not popular. The rate of antenatal diagnosis varies between countries, including between developed countries [7e10]. Further, the lack of understanding about the anatomical structures also makes it difficult to interpret FECG findings. A database of fetal heart anatomies can be used to better understand the anatomical features of the different CHDs and to virtualize FECG using three-dimensional (3-D) software. The sectional anatomical and 3-D models of the adult heart [11e16] from the first Chinese Digital Human [17] and Visible Human Project [18] have been applied in scientific research, school education, and clinical research. However, no research regarding the applicability of a fetal heart database has been reported. In 2010, we reported the first-ever database established for the normal fetal heart anatomy [19]. Since then, we have established a database with fetal heart images of 40 cases with CHD. This paper reports the characteristics of these cases and presents the results of

http://dx.doi.org/10.1016/j.tjog.2015.01.002 1028-4559/Copyright © 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.

J.-X. Gao et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 284e289

our preliminary analysis of the clinical application value of our database.

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removed, along with a 0.5-cm-thick border of lung tissue on the sides to maintain the maximum size that would fit into the freezing microtome.

Materials and methods Source of the specimens

Installation of the logo bar and establishment of the original database of transverse sections

Forty fetal samples from induced labor due to CHD with or without malformations in other systems were included in this study. All samples were Chinese fetuses. This study was conducted in accordance with the Declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Peking University People's Hospital, Beijing, China. Written informed consent was obtained from all participants' guardians. Pretreatment of the samples The skin and subcutaneous tissue of the pleura were cut along the left sternal border of the fetal sample, and the tissue samples were fixed with 4% formaldehyde for 4e8 weeks. Subsequently, the thymus, lungs, heart, trachea, esophagus, descending aorta, and part of the inferior vena cava were separated and removed as a whole from the thoracic cavity. Afterward, we continued fixing the thoracic viscera for 2e4 weeks. Next, the heart sample was

A square organic glass box (size: 4 cm 4.5 cm 4.5 cm or 5 cm 5.5 cm 5.5 cm), with hole grooves of 0.3 cm in diameter in the four corners of the box cover and base was used. According to the different gestational ages, we placed the pretreated heart sample into the box vertically to submerge the heart sample in optimum cutting temperature compound and covered the box. Next, we inserted 2e4 pencil leads (0.3 cm in diameter) vertically from the hole in the cover to the base hole groove. After being frozen for 4 hours at 25 C, we took out the content of the box as a whole and fixed it using a freezing microtome (CM1900; Leica, Wetzlar, Germany). From the base to the top, the heart samples were cut transversely to 60-mm thickness, and every section was macroshot with a digital camera (EOS 5D Mark II; camera lens, EF180mm f/3.5L Macro; Canon, Tokyo, Japan); the anatomical ultrathin cross-sectional images of the different fetal CHDs obtained were used to build the original database. Each

Table 1 Forty case cross-section databases of fetal heart with congenital heart disease (CHD). CHD types

Gestational age (wk)

Case number

Diagnostic basis

ECD ECD ECD þ DOVT þ PAS þ APVC ECD þ APVC TGA (completed) þ HLHS TGA (completed) TGA (completed) þ PAS þ VSD TGA (corrected) PTA þ VSD PTA þ SASV PTA þ VSD PTA þ CH HLHS þ PSVC HLHS þ MA þ TGA HLHS þ CoA þ VSD HLHS þ DOVT þ VSD HLHS þ TGA þ PAS þ MA SASV EFE NVM TA þ VSD TOF TOF TOF þ VR TOF þ RAA TOF þ IIVC MA þ VSD RAD PAS þ VSD RVD RVD þ PA CoA þ VSD RAA Atrial myxoma Rhabdomyoma of heart Ebstein anomaly þ VSD Ebstein anomaly þ effusion

25 12 28 22 25 24 26 28 15 16 28 12 35 25 22 22 24 24 30 31 25 22 25 32 27 25 13 23 21 25 31 21 27 23 29 26 32

2 1 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 1 1 1 1

Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy Biopsy

APVC ¼ anomalous pulmonary venous connection; CH ¼ cystic hygroma; CoA ¼ coarctation of aorta; DOVT ¼ double outlet of right ventricle; ECD ¼ endocardial cushion defect; EFE ¼ endocardial fibroelastosis; HLHS ¼ hypoplastic left heart syndrome; IIVC ¼ interruption of inferior vena cava; MA ¼ mitral atresia; NVM ¼ noncompaction ventricular myocardium; PA ¼ pulmonary atresia; PAS ¼ pulmonary artery stenosis; PSVC ¼ persistent left superior vena cava; PTA ¼ persistent truncus arteriosus; RAA ¼ right aortic arch; RAD ¼ diverticulum of right atrium; RVD ¼ right ventricular dysplasia; SASV ¼ single atrium and single ventricle; TA ¼ tricuspid atresia; TGA ¼ transposition of the great arteries; TOF ¼ tetralogy of Fallot; VR ¼ vascular ring; VSD ¼ ventricular septal defect.

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image entered in the database contained 2e4 identification points produced by the pencil leads.

Results Establishment of the anatomical ultrathin cross-section database

Image registration to the database and application of the 3-D software Taking the identification points as reference points, we registered every image to eliminate the shift and rotation caused by photography. The files were converted from JPEG format to BMP format, and the database was imported into Amira 5.3.1 3-D software (FEI company, Hillsboro, Oregon, the United States) to evaluate its clinical application.

We established a cross-sectional database containing 40 cases, and > 20 different types, of fetal CHDs, including tetralogy of Fallot, complete endocardial cushion defect, pulmonary artery atresia, transposition of great arteries, persistent truncus arteriosus, Ebstein anomaly, hypoplastic left heart syndrome, pulmonary stenosis, atrial myxoma, anomalous pulmonary venous drainage, noncompaction of ventricular myocardium, and rhabdomyoma of the heart (Table 1). For each case, there were 600e700 cross-

Fig. 1. Four-chamber view of fetal hearts with different kinds of CHD, including anatomic image and the corresponding ultrasound image. (A) Fetal heart with tricuspid atresia; (B) fetal heart with right ventricular dysplasia; and (C) fetal heart with noncompaction ventricular myocardium. CHD ¼ congenital heart diseases; LA ¼ left atrium; LV ¼ left ventricle; RA ¼ right atrium; RV ¼ right ventricle; TV ¼ tricuspid valve.


sectional images originally saved in JPEG format at a resolution of 3744 pixels 5616 pixels. The database images not only clearly present the atria, ventricles, and great vessels, but also distinctly show the cardiac valves, chordae tendineae, musculi papillares, coronary sinus, and coronary artery and its branches. More importantly, they reflected the anatomical characteristics of the different fetal CHDs (Fig. 1). The function of the anatomical ultrathin cross-section databases After registering and format conversion, we imported the database of transverse sections into the Amira 5.3.1 3-D software, whereby the following functions could be realized: (1) based on the original database of transverse sections, databases of sagittal and coronal sections could be reconstructed; (2) the original and reconstructed databases could be displayed continuously and dynamically and rotated in arbitrary anglesdthey could also be displayed synchronically (Fig. 2); and (3) sections from the dynamic display and rotation correspond well to the FECG images of the sections (Fig. 3). Discussion Advantages of the database compared with the traditional anatomy method The fetal heart structure is very subtle. Although the traditional anatomical method can present partial anatomical features, it still possesses the following disadvantages: (1) the anatomized fetal heart sample cannot show the integrity and maintain its natural state; (2) during the anatomical progress, some tiny structures such as the valves, chordae tendineae, and coronary artery are destroyed, and identifying small lesions of the fetal heart is difficult; and (3)

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the sample can only be kept for a limited period, after which it becomes useless as a source. In this research, we fixed the fetal samples in formaldehyde and cut the thoracic viscera as a whole to maintain the natural state of the heart as much as possible. At the present time, our database with 60-mm thick tissue samples, has the thinnest heart sections. Further, it not only presents the valves, chordae tendineae, and other tiny structures, but also enables us to discover some tiny pathological changes that are difficult to display when using the traditional anatomy method. Moreover, with the application of 3-D software, the section and spatial anatomical features can be represented, and such information can be used to understand the spatial anatomical features of different kinds of fetal CHD. In addition, the database can be kept for a long period and used repeatedly, and we can establish a digitized library of fetal heart anatomies by accumulating more fetal CHD data. Digitized library of different types of fetal CHD available for education and training Our original and reconstructed databases could not only be displayed continuously and dynamically and rotated in arbitrary angles, but also be displayed synchronically. With the application of these functions, the digitized library can be used as a teaching and research base at medical colleges and universities, allowing students a better grasp of the anatomical characteristics of different kinds of fetal CHD. Providing an anatomical foundation for the continuous transverse scan of the fetal heart Sections from the dynamic display and rotation correspond well to the FECG images in this study. Thus, the digitized library can be

Fig. 2. The common venous cavity of anomalous pulmonary venous connection presented at different direction synchronously with the application of three-dimensional software: (A) cross-section image; (B) sagittal image; (C) coronal image. CV ¼ common vein; DAO ¼ descending aorta; ESO ¼ esophagus; LA ¼ left atrium; PV ¼ pulmonary vein; RA ¼ right atrium.

Fig. 3. Cross-section images of fetal heart with tetralogy of Fallot, including anatomic image and the corresponding ultrasound image: (A) four-chamber view; (B) outflow tract of left ventricle; (C) outflow tract of right ventricle; (D) arterial duct arch; and (E) aortic arch. AA ¼ aortic arch; AAO ¼ ascending aorta; ADA ¼ arch of ductus arteriosus; DAO ¼ descending aorta; LA ¼ left atrium; LV ¼ left ventricle; LVOT ¼ outlet of left ventricle; RA ¼ right atrium; RV ¼ right ventricle; RVOT ¼ outlet of right ventricle.


used as a prenatal diagnosis training base in which ultrasound trainees can not only study the anatomy of different types of fetal CHD, but also virtualize FECG. In particular, the digitized library could provide an anatomical foundation for the continuous transverse scan of the fetal heart. Compared with those of adults, the fetal costa and sternum ossification are inconspicuous. Without the influence of lung gas, we can continuously observe the fetal cardiac anatomical structures from arbitrary angles when avoiding the influence of the spine. For this reason, continuous scanning of the fetal heart can be simpler than the adult echocardiographic technique. In 2001, Yagel et al [20] reported a screening method for comprehensive cardiac evaluation by five short axis views. In 2008, the International Society of Ultrasound in Obstetrics and Gynecology published a similar consensus, suggesting that fetal heart anatomical features can be evaluated by continuous transverse scanning [21]. As a result, the fetal heart transverse sweep technique has become popular and increasingly accepted in recent years. Understanding the anatomical cross-sections of different types of CHD is important for the application of the transverse sweep technique. The database reported herein represents the first attempt to provide an anatomical foundation for the continuous transverse scan of the fetal heart. For example, in July 2013 and April 2014, we successfully organized a national continuing medical education project, the so-called Cross-section databases of fetal congenital heart disease and prenatal ultrasound diagnosis project, which was attended by up to 300 participants each session. This project has been highly praised by the participants. Establishment of an anatomy atlas of fetal CHDs The original cross-sectional and reconstructed coronal and sagittal databases (600e700 images per case per database) of fetal CHD cases included nearly 2000 tissue section samples. They successively reflect the characteristics of the auricular vein connection, atrioventricular connection, ventricular artery connection, and vessels of the heart base. Moreover, some special sections can be obtained by rotating the database images in arbitrary angles, and sections that reflect the pathological features of different CHDs can be selected to establish an anatomy atlas of fetal CHDs. Conflicts of interest The authors declare that they have no conflict of interest. Acknowledgments This work was supported by The Capital Project of Fund Development (2011-4022-07).

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