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In this section, we briefly review the key features that CDUS can demonstrate in the fetal heart. Subsequently, we will also review the use of CDUS/PDUS to assess the peripheral circulation.
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CDUS represents a mandatory component of fetal echocardiography.6 This imaging technique should be used to derive functional information on the fetal heart, but it can also be used to obtain anatomic information in the case of impaired acoustic window, eg, due to maternal obesity or fetal position. In the normal fetal heart, CDUS is used to demonstrate regular blood flow across atrioventricular and semilunar valves (see Figure 12-3). The flow across these valves should be laminar, which means that it is displayed as a smooth red/blue color with only minor changes to lighter hues of the same color across the valves if the Nyquist limit is almost reached by the blood flow velocity (the Nyquist limit is the maximum velocity allowed for any given PRF value after which the color map is inverted). At the same time, CDUS should rule out any valve regurgitation or stenosis. The former is diagnosed whenever retrograde, high-velocity, turbulent blood flow is detected during the phase of the cardiac cycle in which there should be no leakage across that valve, eg, during systole for atrioventricular valves (see Figure 12-4A). Heart valve stenosis is diagnosed when turbulent, high velocity blood flow is detected through a valve during the phase of the cardiac cycle in which it should indeed be open, eg, during systole for semilunar valves (see Figure 12-4B). As previously discussed, CDUS can also be used to confirm retrograde blood flow across the ductus arteriosus or the aortic arch in the case of complete outflow tract obstruction: the former is detected in cases of pulmonary valve atresia with an intact ventricular septum (Figure 12-6), the latter in cases of aortic atresia usually in the context of a hypoplastic left heart syndrome (Figure 12-7). The importance of the detection of retrograde blood flow across the ductus arteriosus or aortic arch is due to the fact that this finding identifies ductus dependency, and consequently tags the heart defect as a neonatal emergency. In fact, this means that that particular congenital heart disease requires the ductus to be patent for the neonate to survive. As soon as the ductus arteriosus closes, the neonate develops acute cardiac failure and dies. These concepts are more extensively illustrated in Chapter 6, where major congenital heart diseases are described.
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In fetal echocardiography, CDUS is also used to confirm abnormal anatomy as seen on gray-scale imaging, whenever the confidence of the diagnosis is questionable. Examples of this confirmatory role of CDUS are shown in Figures 12-8 and 12-9. On the 4-chamber view CDUS can demonstrate (see Figure 12-8) the single atrioventricular orifice in atrioventricular septal defect (Figure 12-8C); the absent filling of one hypoplastic chamber in the case of tricuspid atresia or hypoplastic left heart syndrome; severe insufficiency of the tricuspid valve in the case of Ebstein anomaly or pulmonary atresia with intact ventricular septum (Figure 12-8A); ventricular disproportion in the case of aortic coarctation (Figure 12-8B); and confirmation of the existence of a ventricular septal defect by showing bidirectional shunt across it (Figure 12-8D). When used to assess the outflow tracts, CDUS can demonstrate (see Figure 12-9) the double right ventriculoarterial connection in double-outlet right ventricle; the ventriculoarterial discordance in transposition of the great arteries; and the malalignment ventricular septal defect with overriding aorta in tetralogy of Fallot.
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If used routinely while scanning, it can also reveal unforeseen findings, such as small muscular ventricular septal defects not visible on gray-scale ultrasonography (Figure 12-10A), or mild flow insufficiency across a sonographically unremarkable tricuspid valve (Figure 12-10B), which could represent a finding associated with trisomy 21 in both the first and second trimesters.7
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However, CDUS can also be effectively used to assess central cardiac connections when the acoustic window is inadequate during the screening examination of obese women. This challenge is becoming a pressing problem due to the global trend towards obesity.8,9 In instances when even the existence of the 4-chambers and of the 2 outflow tracts are in doubt, the use of CDUS (with the lowest transmission frequency setting) can at least demonstrate the atrioventricular and ventriculoarterial connections that confirm the existence of 2 atria, 2 ventricles, and 2 outflows tracts.9
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Another relatively novel application is 3D or 4D CDUS/PDUS, which has been recently employed to study heart defects that are difficult to characterize by conventional 2D ultrasonography. In particular, the spatiotemporal image correlation (STIC) algorithm has been advantageously employed to assess the neck vessels and the spatial orientation of the great arteries in conotruncal anomalies (Figure 12-11).10,11 However, this tool can also be used to teach normal anatomy in training courses; in this case, the use of the glassbody visualization mode allows direct demonstration of the crossover of the great arteries (Figure 12-12A), and makes the identification of the pulmonary veins draining into the left atrium much more straightforward (Figure 12-12B).
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Another application of CDUS is early fetal echocardiography. This examination is performed trasvaginally or transabdominally from 12 to 15 weeks of gestation for selected indications.12,13 A list of the most common indications for early fetal echocardiography follows, in decreasing order of frequency:
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Enlarged nuchal translucency (NT) with normal karyotype
Extracardiac anomaly detected on early fetal ultrasound
Two or more siblings/relatives with major congenital heart disease
Reassurance after a previous child has died of major congenital heart disease
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In early pregnancy, the recognition of the central cardiovascular connection is greatly enhanced by the identification of blood flow across them. As an example, in Figure 12-13 the sequential analysis of a heart at 12 gestational weeks is shown with the help of tomographic ultrasound imaging, a display technique that provides sequential parallel views of the fetal heart on a single panel. As is evident, the recognition of the cardiac chambers and outflows as well as of the normalcy of flow across them is immediate, if CDUS is used.
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In conclusion, the application of these Doppler techniques, possibly with volume sonography, represents an important component of an advanced examination of the fetal heart. The appropriate and limited use of CDUS may also be very helpful in the screening setting, both to shorten the time of examination and to improve anatomic assessment in cases where the image quality is limited mainly due to maternal obesity.
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Central Venous System
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As mentioned in the introduction to this chapter, CDUS/PDUS represent the best way to study vascular malformations, such as abnormal course and branching of major vessels or arteriovenous malformations. As far as the first group of conditions is concerned, ie, abnormal course and branching of major systemic arteries, we will show several cases in which a diagnosis of such abnormalities may involve clinical considerations. However, imaging techniques that combine CDUS/PDUS and volume sonography can be used to further investigate the flow characteristics of the entire fetal circulation. In particular, with the high-frequency transvaginal ultrasound transducers it is possible to demonstrate the whole fetal circulation as early as the 12th week of pregnancy (Figures 12-14 and 12-15). Using very sensitive power Doppler algorithms, it is also very simple to demonstrate normal vascular supply to most organs from 12 weeks' gestation onward (Figures 12-16 and 12-17). Using the same technique, it is possible to demonstrate the origin and course of the 2 umbilical arteries and their relationships with the femoral vessels (Figure 12-18).
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Abnormalities of the systemic venous return, such as the umbilical vein and ductus venosus, are relatively common. Starting from the umbilical vein, the first abnormalitiy that can be disclosed by CDUS/PDUS is the persistence of the right umbilical vein (Figure 12-19). During the sixth gestational week, the right umbilical vein degenerates while the left one persists. The portion of the left umbilical vein between the liver and the sinus venosus subsequently involutes and the ductus venosus, connecting the left umbilical vein to the inferior vena cava, continues to develop.14 After birth, the left umbilical vein becomes the ligamentum teres. The right umbilical vein can abnormally persist with the left vein and can even completely replace the function of the left umbilical vein. In some cases, anomalous venous return has been reported to bypass the liver with aberrant drainage of blood directly into the right atrium. Persistence of the right umbilical vein has an incidence of about 1:450 in fetuses.15 Sonographically, this anomaly can be diagnosed because the intra-abdominal portion is seen to the right of the gall bladder, which is slightly displaced towards the midline. In contrast, the more frequent persistence of a left umbilical vein occurs when the midline vessel and the gall bladder are normally found in the right abdomen (see Figure 12-19). This finding can be considered as a normal variant because it is not associated with increased risk of fetal demise or associated structural anomalies.15
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Occasionally, CDUS/PDUS are used to characterize a dilated intra-abdominal portion of the umbilical vein (Figures 12-20 and 12-21). This sonographic finding can involve the proximal intra-abdominal tract or the central intrahepatic umbilical vein. Some studies have reported an increased risk of fetal demise and structural abnormalities with umbilical vein varices.16,17 Therefore, it has been proposed that early delivery at 32 to 34 weeks might avoid the risk of late unexplained fetal death associated in affected fetuses.16 However, this increased risk is probably limited to those cases in which there is abnormal, turbulent, high velocity blood flow across or near the varix (see Figure 12-20). In most cases, the risks related to this anomaly cease with delivery, because the intrahepatic portion of the umbilical vein will involute after the cord is severed. The only exception involves much more rare cases in which the varix is associated with partial failure to form critical porto-umbilical anastomoses.18 These fetuses can develop abnormal portohepatic shunting that may be responsible for abnormal liver function tests such as galactosemia and hyperammonemia.19 However, the shunt usually disappears after a few weeks and the liver function tests return to normal.
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A third example of abnormal central venous return involves the ductus venosus. This vessel can be completely absent and replaced by collateral venous drainage that bypasses the liver. Collateral vessels have been found to course along the anterior liver surface before draining directly into the right atrium or into the infracardiac portion of the inferior vena cava (Figure 12-22). This anomaly is important to detect because it is often associated with signs of cardiac failure (pleural effusions, hydrops) and fetal anomalies.18
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Abnormalities of the venae cavae can also occur during fetal development. In the early embryo, there are 2 superior venae cavae; the left one usually involutes, and the cerebral venous return from the left side is directed into the right superior vena cava through the innominate vein. However, the left superior vena cava more rarely persists either in association with the right one or as the only venous return from the fetal head. Usually, when it coexists with the right superior vena cava, the vein may drain directly into the right atrium or, more frequently, into the coronary sinus, which will consequently dilate to accommodate increased blood flow (Figure 12-23). Although this anomaly has been associated with major structural abnormalities, most investigators do not consider it clinically significant as an isolated finding.20,21
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Another aberration of the systemic venous return development is represented by interruption of the inferior vena cava, usually in the context of cardiosplenic syndromes (left atrial isomerism) (Figure 12-24). In these cases, the systemic venous return often relies on either azygos or hemi-azygous continuation into a right superior vena cava or persistent left superior vena cava, respectively (Figure 12-25).
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Major anomalies of the aortic arch, such as right or double arch, can occur with a variety of neck vessel branching patterns.22 In this section, we present only those variants associated with a retrotracheal sling, because newborn infants can develop dysphagia and respiratory embarassment due to esophageal and/or tracheal compression. The reason why we are illustrating these anomalies in this chapter is that these are only rarely detected on gray-scale ultrasonography but are readily detectable using CDUS/ PDUS. Doppler imaging techniques can be combined with volume sonography to improve characterization of these lesions. A retrotracheal sling can develop as a result of several aortic branching abnormalities that include double aortic arch, right aortic arch with aberrant origin of the right left subclavian artery, and left arch with an aberrant origin of the right subclavian artery (Figure 12-26). The latter anomaly, namely the aberrant right subclavian artery, has been found to be associated with Down syndrome both after birth and in utero.23
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The Normal Cerebral Circulation
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Contemporary ultrasound equipment allows a detailed assessment of the cerebral circulation, especially if the examination is carried out with a transvaginal approach. In addition, the use of high-frequency transducers has made the assessment of the cerebral circulation feasible also in the late first trimester. We will initially review the application of CDUS/PDUS for evaluating the normal cerebral circulation in the first trimester fetus. The use of these imaging modalities will also be described in the second trimester fetus when assessment of the cerebral arteries and veins are more likely to be clinically relevant.
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The latest advances in 4D ultrasonography and Doppler technologies permit demonstration of the cerebral circulation as early as 8 to 9 weeks of gestation. At this stage, both PDUS and B-flow techniques can be used to demonstrate the main branching of both internal carotid arteries as well as the basilar artery. Thereafter, the cerebral arteries and veins can be thoroughly studied. Both the spinal and the cerebral vessels can be clearly demonstrated at 12 to 14 weeks of gestation (Figure 12-27).
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During the second and third trimesters, transvaginal neurosonography24 can be used to demonstrate the cerebral blood supply, from the main arteries to the tiny parenchymal branches. The normal cerebral circulation is demonstrated in Figures 12-28,12-29, and 12-30. On the midsagittal view, the anterior cerebral artery with the pericallosal artery and its branches are visible (see Figure 12-28). Using the same plane, the larger veins are shown (see Figure 12-29), with the straight sinus coursing from the posterior aspect of the corpus callosum to the torcular herophili, and the superior sagittal sinus coursing under the calvarial vault. Close to the cranial base, the basilar artery and the internal carotid arteries are visible. If the fetal head is scanned from the posterior fontanell, the cerebellar blood supply and the torcular herophili can also be studied (see Figure 12-29). If attention is focused on the cortex, reducing the PRF to show low velocity vessels, tiny branches can be seen penetrating the white matter in a radial pattern (see Figures 12-29 and 12-30).
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Considering the high resolution with which the normal circulation of the fetal brain can be demonstrated, it is not surprising that CDUS/PDUS can be used to both demonstrate blood vessel abnormalities (eg, vein of Galen aneurysm) and confirm abnormal central nervous system anatomy by demonstration of its abnormal vessel course and/or branching (eg, incomplete branching of the pericallosal artery for agenesis of the corpus callosum).
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Cerebral Arteriovenous Malformations
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The most important group of extracardiac anomalies that can be evaluated using CDUS/PDUS are the arteriovenous malformations that usually affect the cerebral circulation. It is believed that these malformations result from a disorder of the embryonic capillary maturation process, which leads to the formation of an arteriovenous shunt.25 These arteriovenous malformations generally consist of a feeding artery, 1 or more mostly dilated draining veins, and a centrally located vascular nidus. The nidus itself is a conglomerate of atypical vessels of variable diameter and wall thickness, which does not contain normal capillaries. Alternatively, the central nidus can be absent and a large fistula connects the feeding artery with an aneurysmatic vein. These vascular abnormalities are relatively rare in the fetus, but can be well characterized by CDUS/PDUS. In most cases, cardiac overload or overt decompensation is already present by the time of diagnosis. The most common form of cerebral arteriovenous malformation in the fetus is represented by an aneurysm of the vein of Galen.26,27 However, the architecture of the vascular malformation can vary significantly, with several variants being described after birth, when a detailed angiographic assessment of the lesion can be carried out.25 The most common sites of cerebral arteriovenous malformations include, in addition to the vein of Galen, the torcular herophili and the anterior cerebral artery.
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In the fetus, the diagnosis of a cerebral arteriovenous malformation is suspected on 2D ultrasonography when a large anechoic area is seen on the midline of the fetal brain, resembling, to a certain extent, a severely enlarged third ventricle (Figure 12-31A). The diagnosis is then confirmed by CDUS/PDUS that demonstrate the turbulent and vascular nature of the lesion (Figure 12-31B). As already mentioned, the site and the architecture of the vascular anomaly may vary, but it can be thoroughly mapped by CDUS/PDUS. Another vein of Galen aneurysm is shown in Figure 12-32. In most cases, severe cardiac overload is already present at the time of diagnosis (Figure 12-31D), and in some fetuses, cerebral hemorrhage and secondary ventricular dilatation may also be present (Figure 12-31A).
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Other Conditions Associated with Arteriovenous Shunt
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This group of anomalies includes neoplastic conditions characterized by a high blood flow, such as sacrococcygeal teratoma, twin-to-twin transfusion syndrome, and twin reversed arterial perfusion or TRAP sequence.
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As far as the first condition is concerned, there is little interest in mapping the vascular bed of a large tumor, unless direct fetal interventional surgery is planned, in order to reduce the risk of high-output cardiac failure. In this case, it is important to identify the best vessel for possible alcohol ablation or laser therapy (Figure 12-33).28
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TRAP sequence, acardiac anomaly, or chorioangopagus parasiticus (acardius) are synonymous terms referring to a very rare complication of monochorionic multiple pregnancies. In this condition, the acardiac twin is abnormally perfused by a structurally normal co-twin (the pump twin) through a single superficial artery-to-artery placental anastomosis. The condition results in retrograde arterial blood flow from the "pump twin" towards the affected fetus. The affected fetus is commonly referred to as a "parasite twin" because it is hemodynamically dependent upon the pump twin (Figure 12-34). The main prenatal problems associated with the TRAP sequence are congestive heart failure of the pump twin, polyhydramnios, and preterm delivery, although intrauterine death of the pump twin has been reported even in the absence of such features.29 In the TRAP sequence, the anastomosis between the pump twin and the acardiac twin can take several distinct forms that include a Y shaped, velamentous insertion of one cord, or with different insertions of the cord on the parasite twin. CDUS/PDUS is of fundamental importance to trace and display the circulatory anatomy for presurgical planning of cord coagulation in twin pregnancies with TRAP sequence.30
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