Screening ultrasonography is generally performed with grayscale two-dimensional (2D) ultrasonography, whereas more advanced studies can now utilize a vast array of technologies including three-dimensional (3D) ultrasonography, color Doppler sonography, power Doppler sonography, pulsed-wave Doppler sonography, continuous-wave Doppler sonography, tissue Doppler sonography, and B-flow imaging. Most of these techniques are mastered by experienced operators only, but color Doppler (CDUS) and power Doppler (PDUS) ultrasonography can also be used during the screening examination to reduce examination time and increase diagnostic confidence, especially in the case of an inadequate acoustic window (mainly due to maternal obesity).

Recently, CDUS/PDUS have also been used with 3D and four-dimensional (4D) techniques to display the vascular architecture of several organs and of the heart. In this chapter, the use of CDUS/PDUS is demonstrated to provide sonologists with some useful tools to use in their everyday practice. The use of 3D and 4D CDUS/PDUS for the prenatal diagnosis of congenital heart disease and vascular abnormalities is also discussed.

In the advanced prenatal diagnostic setting, CDUS/PDUS can be used in several ways and with different objectives.

1. 
   

   To demonstrate normal/abnormal fetal cardiovascular anatomy. In fetal echocardiography, CDUS can be employed both in the sequential analysis and for the assessment of cardiac function. In the latter instance, it is used to demonstrate valve insufficiency and stenosis and to diagnose retrograde blood flow in cases of complete obstruction.¹ As far as sequential analysis is concerned, CDUS/PDUS allow faster identification of pulmonary and systemic venous returns and of normal/abnormal ventriculoarterial connections. CDUS is also needed to further examine fetal arteriovenous malformations, such as aneurysm of the vein of Galen, twin-to-twin transfusion syndrome, or TRAP (twin reversed arterial perfusion) syndrome, and sacrococcygeal teratoma.

   
   
2. 
   

   To help identify circulatory characteristics of nonvascular fetal organs. CDUS can also be employed to enhance grayscale recognition of fetal organs, especially in the case of a small acoustic window. For example, the visualization of soft tissues can be severely hampered in patients with severe obesity. In this case, CDUS may be used to trace vessels supplying certain organs to demonstrate their presence or absence. A common application of this principle is demonstrated by the detection of both renal arteries to confirm the presence of both kidneys. Another example is the display of both umbilical arteries in the fetal pelvis to help confirm the presence of the fetal bladder.

   
   
3. 
   

   To guide pulsed-wave Doppler sampling of maternal and fetal vessels. In particular, assessment of uterine artery velocimetry requires the use of CDUS for identifying the corporal branch of the uterine artery at its crossing with the external iliac artery, which cannot be reproducibly visualized on grayscale imaging.² Similarly, optimal peak systolic velocity measurements in the middle cerebral artery require CDUS of a vessel segment that is adjacent to the circle of Willis.³

   
   
4. 
   

   To study the placenta and the umbilical cord, in those rare conditions in which abnormalities of the fetal adnexa are suspected. These include placenta accreta, and velamentous cord insertion or vasa previa.^4,5 In addition, CDUS/PDUS is also used to facilitate the assessment of the cord morphology (ie, single umbilical artery, coiling index, etc).

CDUS/PDUS are important techniques that can provide unique clinical findings often of decisive diagnostic importance. However, extraction of useful information from CDUS/PDUS depends on a correct setup. In fact, different types of applications require completely different and often opposite settings. Major considerations include distance of a vascular structure to the ultrasound transducer, vascular anatomy, blood flow velocity and pulsatility, and likelihood of gross movements in the explored anatomic region. All these variables should be considered prior to using CDUS/PDUS for the Doppler study of maternal or fetal vessels. Examiners should have a practical understanding of the physics of Doppler principles and how to optimize related settings on their ultrasound system. In this chapter, we briefly review the key settings that are used to optimize CDUS/PDUS sensitivity and for specific types of obstetrical investigations.

1. 
   

   Angle of insonation. The key to a successful CDUS/PDUS examination is a correct alignment between the ultrasound beam and the axis of flow in the insonated vessel. This angle should be as close as possible to 0 degrees; beyond approximately 20 degrees, the sampling error and flow evaluation become increasingly unreliable if absolute blood flow is being measured.

   
   
2. 
   

   Arterial blood flow. Arterial blood flow is pulsatile by definition and ranges, in main arteries, from 40 to 80 cm/s at midgestation. These 2 factors should be considered when adjusting the Doppler settings. In particular, for arterial blood flow, the pulse repetition frequency (PRF) should be kept relatively high and the wall filter medium. The probe transmission frequency should be targeted onto the specific region of interest, with lower frequencies selected for deeper examinations. The image persistence should generally be set from low to intermediate for the pulsatile flow to be optimally displayed (Figure 14-1). After adopting these settings, reasonably good CDUS/PDUS images can be obtained both in the fetal heart and peripheral circulation. For the latter, the PRF should be somewhat reduced, considering that the blood flow velocity decreases from the heart to the periphery. Finally, the priority or “balance” should be adjusted to ensure that optimal color Doppler information is displayed without obscuring adjacent grayscale anatomy.

   
   
3. 
   

   Venous blood flow. Venous blood flows have much less pulsatility than arterial ones and show velocities ranging from 10 to 30 cm/s. Hence, the Doppler settings should be adjusted to these figures, ie, low PRF and low wall filter. As for the priority, more emphasis should be applied for the color Doppler signal in order to display small vessels such as the intraparenchymal pulmonary veins, which are typically difficult to visualize on grayscale imaging (Figure 14-2).

   
   
4. 
   

   Differences between CDUS and PDUS. There are some basic differences between CDUS and PDUS that the reader should be aware of. These differences account for the preferential use of one of the 2 Doppler imaging methods for different applications and objectives. The main technical differences between CDUS and PDUS regard the display of velocity, direction, and turbulence of blood flow. In particular, CDUS indicates flow direction within a vessel, displayed by hues of blue and red, with lighter colors indicating higher velocities. Specific types of variance color maps are available in some ultrasound systems that provide additional information about the degree of flow turbulence that is present. At the same time, the laminar versus turbulent aspect of flow can be gathered, with turbulent flow shown as a mosaic flow with mixed blue and red pixels. Conversely, PDUS is also less angle dependent than CDUS, and is more effective in displaying small vessels and low velocities. Some of the newer hybrid forms of PDUS not only provide relatively improved sensitivity for the detection of low blood velocity, but information about flow direction as well. As a result, CDUS is generally employed in the assessment of central cardiovascular connections (Figure 14-3) and of valve competence (Figure 14-4), whereas PDUS is more appropriately used for the assessment of venous return, aortic arch branching patterns, and for the peripheral circulation (Figure 14-5).

A last note regarding the terminology used for CDUS/PDUS when used in association with 3D and 4D ultrasonography: In the literature, several terms have been used, but in this chapter only the simple “glassbody” mode will be used to describe the simultaneous rendering of soft tissues and blood vessels within the same volume data set. This modality is used to display cardiovascular structures within the context of an organ structure that is transparently shown with grayscale imaging.

Fetal Heart

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.

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 14-3). 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 14-4A). 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 14-4B). 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 14-6), the latter in cases of aortic atresia usually in the context of a hypoplastic left heart syndrome (Figure 14-7). 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 20, where major congenital heart diseases are described.

In fetal echocardiography, CDUS is also used to confirm abnormal anatomy as seen on grayscale imaging, whenever the confidence of the diagnosis is questionable. Examples of this confirmatory role of CDUS are shown in Figures 14-8 and 14-9. On the 4-chamber view CDUS can demonstrate (see Figure 14-8) the single atrioventricular orifice in atrioventricular septal defect (Figure 14-8C); 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 (see Figure 14-8A); ventricular disproportion in the case of aortic coarctation (see Figure 14-8B); and confirmation of the existence of a ventricular septal defect by showing bidirectional shunt across it (see Figure 14-8D). When used to assess the outflow tracts, CDUS can demonstrate (see Figure 14-9) 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.

If used routinely while scanning, it can also reveal unforeseen findings, such as small muscular ventricular septal defects not visible on grayscale ultrasonography (Figure 14-10A), or mild flow insufficiency across a sonographically unremarkable tricuspid valve (Figure 14-10B), which could represent a finding associated with trisomy 21 in both the first and second trimesters.⁷

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 toward 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

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 14-11).^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 14-12A), and makes the identification of the pulmonary veins draining into the left atrium much more straightforward (Figure 14-12B).

Another application of CDUS is early fetal echocardiography. This examination is performed transvaginally 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:

• 
  

  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

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 14-13 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.

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.

Central Venous System

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 14-14 and 14-15). 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 14-16 and 14-17). 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 14-18).

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 14-19). 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 toward 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 14-19). 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

Occasionally, CDUS/PDUS are used to characterize a dilated intra-abdominal portion of the umbilical vein (Figures 14-20 and 14-21). This sonographic finding can involve the proximal intra-abdominal tract or the central intrahepatic umbilical vein. Older studies have reported an increased risk of fetal demise and structural abnormalities with umbilical vein varices, especially if associated with high velocity or turbulent flow in the varicose segment (see Figure 14-21B).^16,17 At that time, it had 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, more recent series do not seem to confirm the aforementioned risk, and therefore current policy in most referral center does not include delivery at 32 to 34 gestational weeks as before, with exceptions to be discussed for any single case. 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 portoumbilical 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.