The precise prenatal diagnosis of abnormal venous connections of the fetal heart is challenging. Anatomical accuracy may be important in determining the best route for postnatal angiography, as well as the prognosis and treatment. This study was designed to determine the value of ‘inversion mode’, a new three- and four-dimensional (4D) rendering algorithm, in the visualization of the spatial relationships of an interrupted inferior vena cava (IVC) with azygos or hemiazygos vein continuation associated with and without heterotaxic syndromes.
Heart volumes were acquired using 4D ultrasonography and spatiotemporal image correlation in cases of interrupted IVC with azygos/hemiazygos continuation (n = 3). Volume datasets were rendered using the ‘inversion mode’ algorithm and abnormal images were compared to those generated from a library of normal fetuses.
The ‘inversion mode’ rendering algorithm allowed the visualization of dilated azygos or hemiazygos veins and their spatial relationships with the descending aorta, the aortic arch, the superior vena cava, and the atria in cases of interrupted IVC with and without heterotaxic syndromes.
The prevalence of abnormal systemic venous return to the heart in children with congenital heart disease is 6.6% (53/800)1, and can reach as much as 70% in complex heart defects such as heterotaxic syndromes2. A frequent venous anomaly associated with these syndromes is the suprarenal interruption of the inferior vena cava (IVC) with an azygos vein continuation. Indeed, this form of abnormal venous return is present in 80% of cases with left isomerism, but in less than 2.5% of cases with right isomerism2. When the suprarenal segment of the IVC is absent, the venous blood from the lower part of the body is usually drained into a dilated azygos and/or hemiazygos vein. These veins ascend in parallel to the right or the left of the descending aorta, before joining their corresponding superior vena cava (SVC)2. The presence of two vessels behind the fetal heart at the level of the four-chamber view has been described as the ‘two vessels sign’. This sonographic sign represents the descending aorta and a dilated azygos3 or hemiazygos vein, and has been proposed to be a reliable indicator of an interrupted IVC with azygos vein continuation3.
Prenatal visualization of abnormal venous connections to the fetal heart with two-dimensional ultrasonography requires the examiner to continuously scan these vascular structures in multiple scanning planes. This process also involves simultaneous analysis of anatomical structures through mental reconstruction of their spatial relationships. Power Doppler reconstruction of three- and four-dimensional (3D/4D) volume datasets has been used to visualize the spatial configuration of abnormal vasculature in the fetal liver4, 5, other vascular territories5, 6 and abnormal arterial connections to the fetal heart7, 8. Recently, thick-slice 3D and 4D rendering algorithms applied to vascular structures using the minimum projection mode has been used to visualize the spatial relationships of vascular structures at the level of the three-vessel view9. The ‘inversion mode’ is a new rendering algorithm that transforms echolucent structures into echogenic voxels. Thus, anechogenic structures such as the heart chambers, lumen of the great vessels, stomach and bladder appear echogenic on the rendered image, whereas structures that are normally echogenic prior to gray-scale inversion become anechoic10, 11.
The objective of this study was to determine the value of the ‘inversion mode’ rendering algorithm in the visualization of the spatial relationships of an interrupted IVC with an azygos or hemiazygos vein continuation associated with and without heterotaxic syndromes.
We retrospectively reviewed 4D heart volume datasets acquired using the spatiotemporal image correlation (STIC) technique from fetuses with interrupted IVC and azygos continuation (n = 3), and a fetus without heart defects, for which the acquisition sweep incorporated images of the upper abdomen and fetal thorax.
Ultrasound studies were conducted under the protocols approved by the Institutional Review Boards of Wayne State University, William Beaumont Hospital and the National Institute of Child Health and Human Development (NIH). All patients provided written informed consent before participating in the study.
Heart volumes were acquired using 4D ultrasonography with STIC (Voluson 730 Expert, General Electric Medical Systems, Kretztechnik, Zipf, Austria), using a motorized curved-array transducer (2–5 or 4–8 MHz). Once the sagittal view or the four-chamber view of the heart was observed, acquisition was performed using automatic longitudinal sweeps through the fetal chest. Each volume acquisition lasted between 7.5 and 12.5 s, and the acquisition angles varied from 15° to 35°. Whenever possible, acquisition was performed in the absence of fetal movements.
Volume datasets were initially displayed using multiplanar slicing. Using this format, the original plane of acquisition containing the sagittal view of the fetal heart was displayed in Panel A (upper left panel) of the screen. Once a sagittal view of the heart was visualized in Panel A, a transverse orthogonal view of the heart was simultaneously displayed in Panel B (upper right panel) and a coronal orthogonal view in Panel C (lower left panel). Then, volume rendering was applied to the dataset, and a 3D image with the same orientation as in Panel A was displayed in the right lower panel of the screen. In order to obtain ‘inversion mode’ rendered images of the fetal heart and the systemic venous connections, the following algorithm was applied: (1) the region of interest was selected in Panel B, reducing the rendering box height and width to display only the fetal spine, fetal heart and its vascular connections; (2) the direction of view (green dotted line) was set to display the sagittal view of the heart in the anteroposterior projection; and (3) the ‘inversion mode’ rendering algorithm was selected in the ultrasound equipment with the threshold filter set between 70 and 90.
The rendered images with ‘inversion mode’ were rotated to display the right atrium with its venous connections, the longitudinal aspect of the aorta and azygos veins and their corresponding arches. Non-vascular structures were removed from the region of interest using the digital scalpel. However, the fetal spine and stomach were kept and displayed for orientation purposes. In order to obtain optimal images, the 4D image was frozen and the most informative volume dataset within the cardiac cycle was chosen.
Figure 1a displays the four-chamber view of a fetus without heart defects. The corresponding 3D ultrasound image, rendered with the ‘inversion mode’, is presented in Figure 1b.
Figure 2 shows the four-chamber view of the fetal heart in a case of interrupted IVC with azygos continuation associated with omphalocele. The two-vessel sign suggested the presence of a dilated azygos vein. The corresponding 3D ultrasound images rendered with the ‘inversion mode’ are presented in Figure 3. These images allowed the visualization of the azygos vein ascending to the right of the aorta, the arch of the azygos vein entering the SVC, and the spatial relationships between the azygos vein, aortic arch, descending aorta, right atrium and the fetal spine.
Figure 4 displays the four-chamber view of the fetal heart in a case of left isomerism, situs inversus and interrupted IVC with hemiazygos vein continuation. Figure 5 shows the corresponding 3D rendered images obtained with the ‘inversion mode’ algorithm. The interrupted IVC is visualized crossing in front of the descending aorta from right to left, and continuing with the hemiazygos vein. This vein is located on the left of the descending aorta and joins the SVC (located to the left of the aortic arch due to the situs inversus). These findings were confirmed after birth.
Figure 6 displays the four-chamber and three-vessel view of the heart and a transverse view of the upper abdomen in a case of interrupted IVC with hemiazygos vein continuation associated with pulmonary stenosis, ventricular septal defects and persistent left SVC. Figure 7 shows the corresponding 3D ultrasound images rendered with the ‘inversion mode’. The interrupted left-sided IVC continues with a dilated hemiazygos vein, which is located to the left of the descending aorta. This vein joins a persistent left SVC, which drains into a dilated coronary sinus. These findings were confirmed in the postnatal period during the surgical correction of the pulmonary stenosis.
The ‘inversion mode’ rendering algorithm allowed the visualization of dilated azygos or hemiazygos veins and their spatial relationships with the descending aorta, the aortic arch, the SVC, the right atrium and the fetal spine in cases of interrupted IVC associated with and without heterotaxic syndromes.
The term ‘azygos’ is derived from the Greek a zygos, meaning an unpaired structure12. In normal fetuses the azygos vein can be visualized by ultrasound in about half of the fetuses between 22 and 30 weeks of gestation, and in most fetuses during the third trimester using a coronal view of the thorax13. However, the azygos vein diameter ranges only from 1 to 2 mm in the mid-trimester, and from 2 to 4 mm after 30 weeks13. Thus it is difficult to visualize this vessel in a transverse view of the fetal thorax. The azygos vein is located on the right of the descending aorta and has variable anatomical origins, including the right ascending lumbar vein, the right renal vein or the IVC14. The azygos vein drains venous blood from all but the first right intercostal veins, as well as the esophageal, pericardial and subcostal veins14. Similarly, the hemiazygos vein ascends to the left of the spinal column, receiving venous blood from the left lumbar vein, left renal vein and left lower three intercostal veins. At the level of the eighth thoracic vertebral body, the hemiazygos crosses the midline and drains into the azygos vein14. The venous blood from the fourth to the eighth intercostal veins are drained into the accessory hemiazygos vein, which has a variable communication with the hemiazygos vein14.
The embryological origin of the azygos vein is the right supracardinal vein15, while the IVC derives from four embryonic veins: (1) the right vitelline vein, which originates the segment closest to the right atrium; (2) the right subcardinal vein, which originates the segment between the liver and the kidneys; (3) the right supracardinal vein, which gives rise to the segment below the kidneys, and (4) the right and left posterior cardinal veins, which give rise to the sacral segment of the IVC15. When the suprarenal segment of the IVC is absent, venous blood from the lower part of the body usually drains into a dilated azygos vein which ascends parallel, and to the right of, the descending aorta before joining the SVC1, 3, 13. This is clearly visualized in the 4D images rendered with the ‘inversion mode’ in Figure 3. However, alternative pathways for venous drainage have been described16–20, including an interrupted IVC continued with a dilated hemiazygos vein which, in turn, drains into the SVC, as demonstrated in our case of situs inversus (Figure 5). A very unusual variant, which has been reported postnatally18, 19 but not prenatally, is the presence of an interrupted left-sided IVC with hemiazygos vein continuation, joining a persistent left SVC that, in turn, drains into a dilated coronary sinus. This anomaly is clearly visualized using the inversion rendering algorithm in Figure 7.
The absence of the suprarenal portion of the IVC with azygos/hemiazygos continuation hampers proper heart catheterization via the femoral vein1, 21, a procedure used in the neonatal period prior to the surgical correction of associated cardiac anomalies. Thus an accurate prenatal diagnosis of this venous abnormality may help in carefully planning alternative routes for cardiac catheterization1, and can potentially prevent accidental ligation of this vessel with lethal consequences22. In adults, dilated azygos veins have been mistaken for a dissecting aorta, aneurysm or rupture of the aorta21, 23, as well as mediastinal masses24, 25. Thus, a dilated azygos vein should be part of the differential diagnosis.
The ‘inversion mode’ can be used at the time of scanning or after the acquisition of volume datasets with both 3D and 4D techniques. Recently it has been reported that this rendering mode provides more anatomical detail than other rendering algorithms, such as the transparent mode, in the evaluation of hollow anatomical structures11. The quality of the image rendered with the ‘inversion mode’ depends on the quality of the volume dataset acquired. However, adjustments in the threshold, contrast and transparency may improve the quality of the image. In the present study, the best results were obtained by a combination of ‘surface smooth’ and ‘gradient light’ filters.
In summary, the 3D/4D ‘inversion mode’ rendering algorithm can improve the prenatal visualization of a dilated azygos or hemiazygos vein and their spatial relationships with the surrounding cardiovascular structures.