Doppler Ultrasound
The concept of Doppler, which is used in ultrasound, is named after Johann Christian Doppler. The Doppler concept refers to energy that is reflected from a moving boundary, and how the frequency of the reflected energy varies in relation to the moving boundary. In ultrasound terms, Doppler depends on the ability of an ultrasound beam to be changed in frequency when encountering a moving object (red blood cells). After cosmetic manipulation, a waveform is generated that has a clear systolic and diastolic component. Although resistance to blood flow in a given interrogated vessel in the fetus cannot be directly measured, it is possible from the waveform to obtain an index of resistance. Figure 12.3 shows a FVW in the umbilical artery with clear systolic and diastolic cardiac components. Using the peak systolic and peak diastolic values, it is possible to generate Doppler indices of resistances. These include the systolic-to-diastolic (S/D) ratio, pulsatility index, and resistance index.
Because these three indices are functions of the same variables, they are correlated highly with one another. The characteristics of these indices are also shown in
Figure 12.3. The original continuous-wave Doppler technology has been replaced by pulsed-wave Doppler technology. Doppler velocimetry is useful in cases where the fetus is asymmetrically grown due to a uteroplacental etiology.
FIG. 12.3. Umbilical artery Doppler flow velocity waveform demonstrating peak systolic ( A) and peak end-diastolic ( B) velocities. Doppler indices are defined below.
Over the past decade, numerous centers across the United States and in Europe have shed light on circulatory physiology in the normal and growth-restricted fetus.
This has been approached by assessing FVWs in a number of different vessels in the fetus. While these reports provide useful information on any given vessel, reports on one or two vessels alone are not practical from the clinical standpoint since these were primarily cross-sectional studies and did not provide any information on the temporal nature of Doppler changes. After the turn of the 21st century, three reports appeared in the literature that combined longitudinal information on several different vessels with biophysical data obtained from the IUGR fetus. These studies showed that there are sequential changes in Doppler FVW-resistance measurements in different vessels of the severely growth-restricted fetus that is progressively deteriorating.
Normal Fetal Circulation
The umbilical vein leaves the placenta and enters the umbilicus with oxygen and nutrient-rich blood and volume, which are necessary for normal development of the fetus. The venous vasculature of the liver consists of the umbilical and portal veins, hepatic veins, and the ductus venosus. The umbilical vein turns acutely cephalad as it passes through the umbilicus and in the inferior portion of the falciform ligament. The hepatic portion of the umbilical vein then travels horizontally and posteriorly, and bends to the right where it joins the transverse part of the left portal vein. These then join the right portal vein, which branches anteriorly and posteriorly. As the hepatic portion of the umbilical vein bends to the right, the ductus venosus emanates, heading in a posterior and cephalad direction and joins the inferior vena cava (IVC) just below the diaphragm. The three hepatic veins (right, middle, and left) fuse and join at the juncture of the ductus venosus and IVC confluence. The ductus can be visualized easily on both axial and midline sagittal views of the fetus with the use of color velocimetry. Its detection can be enhanced by adjusting the velocity scale and looking for aliasing of the color that indicates the area of highest flow velocity. The ductus venosus plays a critical role in shunting the most oxygenated and
nutrient-rich blood from the hepatic portion of the umbilical vein to the right atrium. More than half of the umbilical vein blood enters the ductus venosus. Portal blood primarily travels to the right lobe of the liver and, as a result, 98% of the blood passing through the ductus venosus comes from the umbilical vein. Some of the blood supply to the left lobe of the liver comes from branches of the umbilical vein, which increases blood oxygen levels in the left hepatic vein compared to the right.
Preferential streaming is a phenomenon that occurs within precordial venous structures and the heart to ensure delivery of the most nutrient-rich blood to the left side of the heart. Briefly, nutrient-rich blood within the ductus and left hepatic vein course preferentially through the posterior and left portions of the column of blood in the thoracic IVC. Blood that is deoxygenated and contains waste products from the abdominal IVC and the right hepatic vein streams, preferentially, along the anterior and right portions of the column of blood in the thoracic IVC. Blood from the superior vena cava joins the blood traveling anteriorly and rightward, enters the right atrium across the tricuspid valve, and exits via the pulmonary artery. Only 10% of the blood from the pulmonary artery enters the pulmonary circulation with the majority crossing the ductus arteriosus into the aorta and the systemic circulation. The posterior and leftward nutrient-rich blood passes across the right atrium through the foramen ovale into the left atrium and out the left ventricle. This ensures that the heart and brain see the most oxygenated blood.
The precordial veins (ductus venosus, hepatic veins, IVC, umbilical and portal veins) have characteristic FVWs as shown by pulsed-wave Doppler velocimetry. The umbilical and portal veins have FVWs that are steady and without pulsations, while the other precordial “systemic” veins have FVWs that reflect the central venous pressures. The following information on the precordial venous FVWs is in reference to the hepatic vein, ductus venosus, and IVC, which have three characteristic phases during a single cardiac cycle. Ventricular systole induces the greatest pressure gradient between the right atrium and the precordial veins during the cardiac cycle. Thus, the blood traveling within these vessels to the heart will have the highest velocity during systole. This is referred to as the “S” component of the FVW.
During early diastolic filling, the second highest velocity of blood through these venous conduits will occur and is referred to as either “D” or “e”. The lowest velocity of blood traveling through these vessels is in late diastole when the atria are contracting; this phase of the FVW is referred to as the “a”-wave. The a-wave in the ductus venosus remains in a positive direction (i.e., blood continues to move toward the heart even during the phase of lowest pressure gradient during atrial contraction). In contrast, the a-wave in the IVC and hepatic veins is in a negative direction indicating that blood is moving away from the heart. The difference in the a-waves between these vessels is important clinically because one can easily confuse reverse flow in the ductus venosus due to the close proximity of these vessels. However, the use of color Doppler and the identification of aliasing should easily distinguish the vessels.
The vast majority of fetal Doppler studies have adopted qualitative indices to describe FVW indices both for arterial flow and venous flow (i.e., S/a ratio of the venous flow of the ductus venosus). For some selected areas of investigation, quantitative parameters are calculated (i.e., peak velocity of the outflow tract of the great vessels). The arterial pipelines to almost all organs have been investigated, including the kidneys, the adrenal glands, the spleen, the lower limbs, the lungs, and the coronary arteries. While these reports provide a piece of the big picture, they do not add to information on fetal status and management gained from cardiac and precordial Doppler studies. As such they are not discussed, but are referenced at the end of the chapter (see “ Suggested Readings”).
Circulation of the IUGR Fetus
A convenient way to clinically approach the variety of fetal vessels that lend themselves to Doppler investigation is to conceptualize the progressive nature of the IUGR disease process and categorize them into three compartments related to the fetal heart:
1. Postcardiac (arterial) Dopplers 2. Cardiac Dopplers
3. Precardiac (precordial or venous) Dopplers.
The three general categories and vessels for each category are shown in Table 12.3. This organization follows the physiologic adaptations by the fetal circulation to progressive abnormalities in the placental vascular tree. Changes in the circulatory architecture of the IUGR placenta create a high-resistance vascular bed, which can be detected by Doppler velocimetry of the umbilical artery and the MCA. These represent the earliest Doppler changes in the IUGR fetus. As the IUGR fetus
deteriorates, one can detect changes in peak velocities of the cardiac outflow tracts and abnormal valvular flow. Precordial or venous Dopplers also change in the IUGR fetus that is decompensating and these vessels include the ductus venosus, hepatic veins, IVC, and intrahepatic and intraamniotic umbilical veins.
TABLE 12.3. Categorization of fetal vessels for Doppler study
Umbilical Artery Doppler
The first fetal vessel to be assessed by Doppler velocimetry FVW analysis was the umbilical artery in the mid-1970s. During the late 1970s and early 1980s, Gill and colleagues and Trudinger and co-workers described the umbilical artery FVW in normal and IUGR pregnancies. In 43 infants with birth weight less than the 10th percentile, Trudinger and colleagues found that the umbilical artery S/D ratio was elevated above the 95th percentile in 85% of cases. This was determined to be related to a decrease in diastolic velocity, which was in turn due to an increase in resistance to blood flow within the placenta. This was supported by work from Giles
and colleagues who correlated the pathologic FVW in IUGR pregnancies with placental lesions. The key concept was that a poorly developed placental vascular bed and progressively abnormal vascularization in the face of increased fetal metabolic demands lead to an increase in placental vascular resistance. This is further supported by research work on hemodynamic bases of waveform changes as affected by increased impedance, changes in the viscosity of the blood, loss of vessel wall compliance, and decreasing inotropic function of the myocardium, all of which contribute to the increased resistance seen in abnormal arterial flow. The umbilical artery was chosen because it was the vessel that extended from the fetus to the placenta and because it reflects resistance patterns downstream within the placenta.
This, in turn, could be identified clinically simply by switching a Doppler beam on the umbilical arteries and looking for an increased S/D ratio (low diastolic velocity) of the arterial waveform. During the 1990s, multiple studies on umbilical artery Doppler velocimetry in the IUGR fetus were followed by three major meta-analyses that showed a reduction in perinatal mortality by approximately one-third when umbilical artery Doppler velocimetry was used as an adjunct to other means of antenatal biophysical testing. In 1993, a European multicentered, prospective, observational trial reported by Karlsdorp and colleagues provided strong evidence suggesting that growth restricted fetuses with abnormal umbilical pulsatility index, with absent diastolic flow and with reverse diastolic flow, had progressively more severe perinatal outcomes.
Middle Cerebral Artery (MCA)
As mentioned earlier in this chapter, prolonged fetal hypoxia as a result of uteroplacental insufficiency will result in a redistribution of blood flow within the fetus in an attempt to deliver more oxygen by increasing volume blood flow to vital organs. This has been shown to be the case in some classic animal studies where prolonged hypoxia leads to blood flow redistribution that is favorable to the heart, brain, and adrenal glands. This redistribution has also been shown by pulsed-wave Doppler velocimetry to occur in human IUGR fetuses. The fetal brain normally has a high-resistance blood flow pattern, which is depicted by low flow velocity at end-diastole, relative to other organs and large vessels. During hypoxia, cerebral vascular autoregulation adjusts blood flow within the brain by decreasing the resistance to flow. The decrease in resistance can be easily detected by pulsed-wave Doppler, which provides an FVW profile that depicts an increase in end-diastolic flow velocity. This will in turn result in a calculated Doppler index of resistance that is low compared to the normally high resistance seen in the cerebral circulation. The most common cerebral artery used for Doppler assessment of the fetal brain-sparing effect is the MCA. The anatomic site and direction of the MCA is perpendicular to the cerebral midline ( Fig. 12.4). This allows for the Doppler beam to be easily positioned along the midportion of the vessel with a minimal angle of insonation, thereby optimizing FVW acquisition. Incidentally, another advantage of the MCA position is that acquisition of a direct measurement of the absolute velocity in cases of fetal anemia (i.e., Rh isoimmunization and parvovirus) is easily obtained at this location.
FIG. 12.4. The ultrasound color Doppler image shows the circle of Willis and the middle cerebral artery branches. Also shown is the near 0-degree angle of insonation and the middle cerebral artery flow velocity waveform. See color figure 12.4.
Both direct and indirect evidence acknowledge that hypoxia is a plausible mechanism for the decrease in MCA pulsatility index (PI) in IUGR. Direct evidence supporting this mechanism was reported by Capponi and associates in a group of IUGR fetuses with an abnormal umbilical PI. They showed that the best predictor of hypoxia at cordocentesis was the MCA PI. Baschat and co-workers provided good indirect evidence in support of hypoxia as a mechanism for the decreased MCA PI. In this study of IUGR fetuses with an abnormal umbilical artery PI, those with a decreased MCA PI had significantly higher nucleated red blood cell counts compared with those who had no Doppler evidence of MCA dilation.
The reduction in abdominal circumference typically precedes Doppler abnormalities in the umbilical artery and the MCA. Doppler studies have shown that the decrease in resistance by the fetal brain and the increase in resistance in the umbilical artery are the earliest arterial changes in Doppler flow velocities in the IUGR fetus. In our experience, they begin more than 3 weeks prior to non-reassuring fetal heart rate recordings. The primary message conveyed by Doppler investigation of the MCA vessel in IUGR fetuses is that the fetus is adapting appropriately to intrauterine hypoxia by “brain-sparing.” Loss of the “brain-sparing” adaptation is thought to be due to loss of cerebral autoregulation, and is considered to be a very late or terminal sign in the decompensating fetus. Before a loss of the “brain-sparing” is acted upon, one must be sure to avoid excessive transducer pressure because this will artificially lower the end-diastolic velocity. Furthermore, one will not see a loss of “brain-sparing”
in the face of otherwise normal Doppler waveforms elsewhere, especially on the venous (precordial) side.
Precordial and Cardiac Flows
Cardiac Doppler studies in the IUGR fetus primarily include assessment of peak velocities of the outflow tracts, left and right ventricular cardiac output, and flow ratios across the valves. Variables that influence these measurements include preload, afterload, and intrinsic contractility of the left and right ventricles, as well as the valve dimensions. Significant contributions have been published on the changes in the atrioventricular filling waveform, and on the flow velocities of the outflow tract of the great vessels. Cross-sectional and longitudinal studies of IUGR fetuses with increased umbilical artery vascular resistance and decreased MCA vascular resistance show a progressive decrease in outflow tract velocity and cardiac output with advancing gestation. Valvular abnormalities tend to occur late in the course of an IUGR fetus that is rapidly decompensating. In one study of 31 IUGR fetuses and 289 normally grown fetuses, tricuspid valve regurgitation (TR) was a frequent, but in most cases, transient finding. Only 2 of the 31 IUGR fetuses showed TR. In one fetus it was only part-systolic, while the other fetus it was severely compromised with abnormal flows in both the arterial and venous system. That TR is a late sign in the course of IUGR has been confirmed elsewhere.
As mentioned earlier, Doppler velocimetry has been used to assess blood flow through the venous circulation of the IUGR fetus including the umbilical vein, ductus venosus, hepatic veins, and IVC. The IVC and the ductus venosus essentially represent the preload profile of the cardiovascular system. Interesting information conveyed by research on these vessels is the significant correlation between abnormal changes in the vessels and acid-base changes of the fetus. Others have correlated these Doppler indices with fetal heart monitoring patterns. Abnormalities in the ductus venosus are characterized by a decrease in velocity of the a-wave, and if the fetus continues to deteriorate, the ductus venosus may show absent or reversed flow velocity of the a-wave. The ductus venosus waveform in a severely growth restricted fetus from 20 to 22 weeks gestation of a mother with severe renal disease and hypertension is shown in Figure 12.5. The a-wave at 20 weeks showed reasonable flow velocity, but progressively deteriorated to intermittent absent and reverse flow velocity.
FIG. 12.5. Ductus venosus flow velocity waveform with abnormal a-waves in a severely growth restricted fetus admitted at 20 weeks gestation. Note the progressive decrease in velocity of flow in the a-wave.
The umbilical vein normally has a steady FVW. The presence of pulsations or nicking in the umbilical vein FVW is a very late sign of the decompensating fetus and likely due to ventricular failure. These pulsations have been shown through animal studies to be initiated from atrial pressure changes and transmitted in a retrograde fashion. In early pregnancy, umbilical venous pulsations can be a normal finding. While assessing the umbilical vein with pulsed-wave Doppler, it is important to be cognizant that fetal breathing can mimic the nicking or pulsations of cardiac origin and these obviously have largely differing implications. Pulsations due to fetal breathing and due to cardiac failure can easily be distinguished by looking for fetal breathing motions or determining the rate of the pulsations seen on the FVW. A
normal umbilical waveform, pulsations due to breathing, and pulsations due to cardiac failure are shown in Figure 12.6.
FIG. 12.6. Umbilical vein flow velocity waveform profiles demonstrating pulsations due to fetal breathing motions and cardiac failure compared to normal.
Temporal Doppler Changes in the IUGR Fetus
While umbilical artery Doppler is useful as an adjunct in antenatal testing, it alone is not capable of distinguishing a decompensating fetus to the extent that morbidity can be reduced. Waiting until there is reverse flow nearly always results in an acidotic fetus with adverse long-term sequelae. It is here where venous Doppler studies will likely play a role in identifying earlier signs of deterioration in the IUGR. Since the late 1990s, more than 100 papers have been published both on the
pathophysiology and clinical correlation of Doppler studies with traditional monitoring and with neonatal outcome. Advances in digital ultrasound technology have had a tremendous impact on the basic knowledge of fetal circulatory adaptation to placental supply deprivation. Clinically, this technology has allowed us to collect
information and take a snapshot of fetal adaptation to placental dysfunction, which in turn can be interpreted as appropriate or inappropriate (i.e., decompensating)
information and take a snapshot of fetal adaptation to placental dysfunction, which in turn can be interpreted as appropriate or inappropriate (i.e., decompensating)