Doppler in Obstetrics by Nicolaides, Rizzo, Hecker & Ximenes
The 11-14 weeks scan by Nicolaides, Sebire, Snijiders & Ximenes
The 18-23 weeks scan by Pilu, Nicolaides, Ximenes & Jeanty

 
Doppler ultrasound provides a non-invasive method for the study of fetal hemodynamics. Investigation of the uterine and umbilical arteries gives information on the perfusion of the uteroplacental and fetoplacental circulations, respectively, while Doppler studies of selected fetal organs are valuable in detecting the hemodynamic rearrangements that occur in response to fetal hypoxemia.
 
FACTORS AFFECTING FLOW VELOCITY WAVEFORM
 
Maternal position
During Doppler studies, the mother should lie in a semirecumbent position with a slight lateral tilt. This minimizes the risk of developing supine hypotension syndrome due to caval compression.
 
Fetal Heart Rate
There is an inverse relation between fetal heart rate and length of cardiac cycle and, therefore, fetal heart rate influences the configuration of the arterial Doppler waveform. When the heart rate drops, the diastolic phase of the cardiac cycle is prolonged and the end-diastolic frequency shift declines. Although the Doppler indices are affected by the fetal heart rate, the change is of no clinical significance when the rate is within the normal range.
 
Fetal breathing movements
During fetal breathing movements, there are variations in the shape of the flow velocity waveforms from fetal vessels and, therefore, Doppler examinations should be conducted only during fetal apnea and in the absence of fetal hiccup or excessive movement.
 
Blood viscosity
Animal studies have demonstrated that increased blood viscosity is associated with reduced cardiac output and increased peripheral resistance, and vice versa. However, Giles et al. were unable to demonstrate a significant association between blood viscosity (measured in post-delivery umbilical cord blood) and impedance to flow in the umbilical artery1.
 
UTEROPLACENTAL CIRCULATION
 
Anatomy
The blood supply to the uterus comes mainly from the uterine arteries, with a small contribution from the ovarian arteries. These vessels anastomose at the cornu of the uterus and give rise to arcuate arteries that run circumferentially round the uterus. The radial arteries arise from the arcuate vessels and penetrate at right angles into the outer third of the myometrium. These vessels then give rise to the basal and spiral arteries, which nourish the myometrium and decidua and the intervillous space of the placenta during pregnancy, respectively. There are about 100 functional openings of spiral arteries into the intervillous space in a mature placenta, but maternal blood enters the space in discrete spurts from only a few of these 2,3.
 
Physiological changes in pregnancy

Physiological modification of spiral arteries is required to permit the ten-fold increase in uterine blood flow which is necessary to meet the respiratory and nutritional requirements of the fetus and placenta. Brosens et al. examined microscopically several hundred placental bed biopsies, seven Cesarean hysterectomy specimens and two intact second-trimester uteri 4. Basal arteries showed no changes, but spiral arteries were invaded by cytotrophoblastic cells and were converted into uteroplacental arteries. These have a dilated and tortuous lumen, a complete absence of muscular and elastic tissue, no continuous endothelial lining, mural thrombi and fibrinoid deposition.

This conversion of the spiral arteries to uteroplacental arteries is termed ‘physiological change’. It has been reported to occur in two stages: the first wave of trophoblastic invasion converts the decidual segments of the spiral arteries in the first trimester and the second wave converts the myometrial segments in the second trimester 5 . As a result of this ‘physiological change’, the diameter of the spiral arteries increases from 15–20 to 300–500 mm, thus reducing impedance to flow and optimizing fetomaternal exchange in the intervillous space.

 
Invasive assessment of blood flow
Assali et al . measured uterine blood flow by placing electromagnetic flow meters in the uterine vessels at the time of hysterotomy for termination of pregnancy and demonstrated that both uterine blood flow and oxygen consumption increase with gestation 6. Browne and Veall injected 24 Na tracer directly into the choriodecidual space of women with anterior placentae and used a Geiger counter to construct decay curves for the falling levels of radioactivity 7 . Although this method was beset by technical failures, it established the commonly quoted figure of 600 ml/min for uterine blood flow at term.
 
Methodology of obtaining waveforms


Campbell et. al. used pulsed wave Doppler to obtain velocity waveforms from ‘arcuate’ arteries, which were described as vessels in the wall of the uterus distinct from the common, internal and external iliac arteries 8 . Trudinger et al . described the use of continuous wave Doppler to obtain velocity waveforms from branches of the uterine artery in the placental bed 9. The placental site was located using real-time ultrasound and the Doppler probe was then pointed at the center of the placental bed and ‘searched’ until characteristic waveforms were obtained. Validation of the method was performed by directing a pulsed wave Doppler facility along the same line and obtaining identical waveforms from subplacental vessels.

Schulman et al . described the use of continuous wave Doppler ultrasound to locate the uterine artery 10 . The Doppler probe was directed into the parauterine area in the region of the lower uterine segment and rotated until a characteristic waveform pattern was recognized. In the early stages of the study, the methodology was validated with Duplex equipment or by in vivo measurements obtained during Cesarean section. They found that patterns of uterine, arcuate and iliac vessels could be differentiated from each other and from other vessels in the pelvis. The presence of an early diastolic notch was noted and was found to disappear between 20 and 26 weeks.

Bewley et al . used continuous wave Doppler to obtain flow velocity waveforms from four fixed points on the uterus Figure 1 11 . The two lower ‘uterine’ sites were insonated in a similar way to that described by Schulman et al . 10, except that the transducer was pointed medially and caudally about 2 cm above and halfway along the inguinal ligament on either side of the uterus. The two upper ‘arcuate’ sites were halfway between the fundus of the uterus and its most lateral point.

Figure 1: Sites of insonation of uterine artey.
Adapted from Bewley et. al. 1989

Arduini et al . compared color flow imaging and conventional pulsed Doppler in the study of the uterine artery 12 . Color flow imaging was used to visualize the flow through the main uterine artery medial to the external iliac artery (Figure 2) and the Doppler sample gate was placed at the point of maximal color brightness. Color flow imaging was found to allow a higher number of reliable recordings to be obtained, to shorten the observation time, and to reduce the intra- and interobserver coefficients of variation.

Figure 2: Ultrasound image with convencional color Doppler showing the uterine artery and the external iliac artery (left). Normal flow velocity waveforms from the uterine artery at 24 weeks of gestation demonstrating high diastolic flow (right).

Impedance to flow in the uterine arteries decreases with gestation (Figure 2). The initial fall until 24–26 weeks is thought to be due to trophoblastic invasion of the spiral arteries, but a continuing fall in impedance may be explained in part by a persisting hormonal effect on elasticity of arterial walls. Impedance in the uterine artery on the same site as the placenta is lower, which is thought to be due to the trophoblastic invasion only taking place in placental spiral arteries and the fall in impedance engendered by this being transmitted to other parts of the uterine circulation through collaterals. The intra- and interobserver coefficients of variation in the measurement of impedance to flow from the uterine arteries are both 5–10%.

Normal Pregnancy - Development of the uterine artery
Normal impedance to flow the uterine arteries in 1º trimester
Normal impedance to flow the uterine arteries in early 2ºtrimester
Normal impedance to flow the uterine arteries in late 2º and 3º trimester
Figure 3: Pulsatility index in the uterine artery with gestation (mean 95th and 5th centiles)
UMBILICAL ARTERY FLOW
The umbilical artery was the first fetal vessel to be evaluated by Doppler velocimetry. Flow velocity waveforms from the umbilical cord have a characteristic saw-tooth appearance of arterial flow in one direction and continuous umbilical venous blood flow in the other. Continuous wave Doppler examination of the umbilical artery is simple. The transducer, usually a pencil-shaped probe, is placed on the mother’s abdomen overlying the fetus and is systematically manipulated to obtain the characteristic waveforms from the umbilical artery and vein. With a pulsed wave Doppler system, an ultrasound scan is first carried out, a free-floating portion of the cord is identified and the Doppler sample volume is placed over an artery and the vein (Figure 4).

Normal Pregnancy - Development of the umbilcal artery
Normal impedance to flow the umbilical arteries and normal pattern of pulsatility at the umbilical vein in 1º trimester
Normal impedance to flow the umbilical arteries and umbilical vein in early 2ºtrimester
Normal impedance to flow the umbilical arteries and umbilcal vein in late 2º and 3º trimester

The location of the Doppler sampling site in the umbilical cord affects the Doppler waveform and the impedance indices are significantly higher at the fetal end of the cord than at the placental end. A possible explanation for this finding is that the fetal placental vascular bed is a low impedance system associated with minimal wave reflection, which explains the presence of continuing forward flow in the umbilical artery during diastole. The closer the measurement site is to the placenta, the less is the wave reflection and the greater the end-diastolic flow. Consequently, the Doppler waveform that represents arterial flow velocity demonstrates progressively declining pulsatility and the indices of pulsatility from the fetal to the placental end of the cord 13.
 
Figure 4a: Ultrasound image with color Doppler showing the umbilical cord, red umbilical artery and blue umbilical vein (left). Normal flow velocity waveforms from the umbilical vein (bottom) and artery (top) at 32 weeks of gestation (right).
Figure 4b: Normal flow velocity waveforms from the umbilical vein (top) and artery (bottom) at 32 weeks of gestation.

There are no appreciable diurnal changes or significant day-to-day variations in pregnancies with normal umbilical arterial Doppler waveforms. Umbilical venous blood flow increases with fetal inspiration (during which the fetal abdominal wall moves inward) and decreases with expiration (during which the wall moves outward). There is also a breathing-related modulation of arterial pulsatility, and umbilical artery Doppler studies should be avoided during fetal breathing. Maternal exercise may cause an increase in fetal heart rate but mild to moderate exercise does not affect flow impedance in the umbilical artery. Umbilical arterial flow waveforms are not affected by fetal behavioral states (sleep or wakefulness). Although, in certain pregnancy disorders (such as pre-eclampsia), fetal blood viscosity is increased, the contribution to the increased impedance in the umbilical artery from viscosity is minimal compared to the coexisting placental pathology. Therefore, the viscosity of fetal blood need not be considered when interpreting the umbilical Doppler indices.

With advancing gestation, umbilical arterial Doppler waveforms demonstrate a progressive rise in the end-diastolic velocity and a decrease in the impedance indices (Figure 5). When the high-pass filter is either turned off or set at the lowest value, end-diastolic frequencies may be detected from as early as 10 weeks and in normal pregnancies they are always present from 15 weeks. Human placental studies have demonstrated that there is continuing expansion of the fetoplacental vascular system throughout the pregnancy. Furthermore, the villous vascular system undergoes a transformation, resulting in the appearance of sinusoidal dilatation in the terminal villous capillaries as pregnancy approaches term, and more than 50% of the stromal volume may be vascularized. The intra- and interobserver variations in the various indices are about 5% and 10%, respectively 14.

 
Figure 5: Pulsatility index in the umbilical artery with gestation (mean, 95th and 5th centiles).
FETAL ARTERIAL FLOW
 
Descending aorta

Velocity waveforms from the fetal descending aorta are usually recorded at the lower thoracic level just above the diaphragm, keeping the angle of insonation of the Doppier beam below 45° (Figure 6). It may be difficult to obtain a low angle because the aorta runs anterior to the fetal spine and, therefore, parallel to the surface of the maternal abdomen. This problem can be overcome, by moving the transducer either toward the fetal head or toward its breech and then tilting the transducer. Diastolic velocities are always present during the second and third trimesters of normal pregnancy, and the pulsatility index (PI) remains constant throughout gestation (Figure 7) 15.

Flow velocity waveforms in the descending aorta represent the summation of blood flows to and resistance to flow in the kidneys, other abdominal organs, femoral arteries (lower limbs) and placenta. Approximately 50% of blood flow in the descending thoracic aorta is distributed to the umbilical artery. With advancing gestation, the PI in the umbilical artery decreases, due to reduced resistance in the placental compartment, whereas, in the aorta, the PI remains constant. The absence of a change in PI suggests the presence of a compensatory vasoconstrictive mechanism in the other major branches of the aorta distribution, such as the extremities.

Figure 6: Parasagittal view of the fetal trunk with superimposed color Doppler showing the descending aorta (left). Flow velocity waveforms from the fetal descending aorta at 32 weeks of gestation demonstrating positive end-diastolic velocities (right).
Normal Pregnancy - Development of the Descending Aorta
Color Doppler Energy with visualization of the Aortic Arch and Descending thoracic aorta
Normal flow of the descending thoracic aorta in 2º and 3º trimesters
Figure 7: Pulsatility index (left) and mean blood velocity (right) in the fetal aorta with gestation (mean, 95th and 5th centiles).
 
The mean blood velocity increases with gestation up to 32 weeks and then remains constant up to 40 weeks, when there is a small fall (Figure 7) 15.
Renal Artery
Color Doppler allows easy identification in a longitudinal view of the fetal renal artery from its origin as a lateral branch of the abdominal aorta to the hilus of the kidney (Figure 8). Diastolic velocities may be physiologically absent until 34 weeks, and then increase significantly with advancing gestation. The PI decreases linearly with gestation, indicating a fall in impedance to flow, and presumably an increase in renal perfusion 16,17. This may offer an explanation for the increase of fetal urine production that occurs with advancing gestation 18.
Figure 8a: Parasagittal view of the fetal trunk with Power Color Doppler showing the renal artery originating from the descending aorta (left). Flow velocity waveforms from the renal artery and vein at 32 weeks of gestation with physiologically absent end-diastolic velocities (right).
Figure 8b: Flow velocity waveforms from the renal artery and vein at 32 weeks of gestation with physiologically absent end-diastolic velocities (right).
Cerebral Arteries
With the color Doppler technique, it is possible to investigate the main cerebral arteries such as the internal carotid artery, the middle cerebral artery, and the anterior and the posterior cerebral arteries and to evaluate the vascular resistances in different areas supplied by these vessels.

A transverse view of the fetal brain is obtained at the level of the biparietal diameter. The transducer is then moved towards the base of the skull at the level of the lesser wing of the sphenoid bone. Using color flow imaging, the middle cerebral artery can be seen as a major lateral branch of the circle of Willis, running anterolaterally at the borderline between the anterior and the middle cerebral fossae (Figure 9). The pulsed Doppler sample gate is then placed on the middle portion of this vessel to obtain flow velocity waveforms. Due to the course of this blood vessel, it is almost always possible to obtain an angle of insonation which is less than 10°. During the studies, care should be taken to apply minimal pressure to the maternal abdomen with the transducer, as fetal head compression is associated with alterations of intracranial arterial waveforms 19.
Figure 9: Transverse view of the fetal head with color Doppler showing the circle of Willis (left). Flow velocity waveforms from the middle cerebral artery at 32 weeks of gestation (right).
Normal Pregnancy - Development of the Middle Cerebral Artery
Color Doppler Energy with visualization of the Circle of Willis and the Middle Cerebral Artery
Normal flow of the Middle Cerebral Artery in 1º trimester
Normal flow of the Middle Cerebral Artery in 2º and 3º trimester
Figure 10: Pulsatility index (left) and mean blood velocity (right) in the fetal middle cerebral artery with gestation (mean, 95th and 5th centiles).
In healthy fetuses, impedance to flow in the fetal aorta does not change with gestation during the second and early third trimesters of pregnancy, but it subsequently decreases (Figure 7) 15,20–22. The PI is significantly higher in the middle cerebral artery than in the internal carotid artery or in the anterior and posterior cerebral arteries. It is, therefore, important to know exactly which cerebral vessel is sampled during a Doppler examination, as a PI value that might be normal for the internal carotid artery may be abnormal for the middle cerebral artery. The use of color Doppler greatly improves the identification of the cerebral vessels, thus limiting the possibility of sampling errors. The blood velocity increases with advancing gestation, and this increase is significantly associated with the decrease in PI (Figure 10).
Figure 11: Transverse view of the fetal head color 3D powerDoppler showing the circle of Willis with digital subtraction of the grayscale.
Other arterial vessels
Improvements in flow detection with the new generation of color Doppler equipment have made it possible to visualize and record velocity waveforms from several fetal arterial vessels, including those to the extremities (femural, tibial and brachial arteries), adrenal, splenic (Figure 12), mesenteric, lung, and coronary vessels. Although study of these vessels has helped to improve our knowledge of fetal hemodynamics, there is no evidence at present to support their use in clinical practice.
Figure 12: Flow velocity waveforms from the fetal splenic artery/vein at 32 weeks of gestation in a normal fetus.
Figure 13:Color Doppler showing the femural flow (left). Flow velocity waveforms from the femural artery at 26 weeks of gestation in a normal fetus (right).
FETAL CARDIAC FLOW
Examination of the fetal heart using Doppler ultrasound is achieved similarly to the examination in gray-scale mode. Several planes including the abdominal view, four-chamber, five-chamber, short-axis and three-vessel views have to be assessed in order to get spatial information on different cardiac chambers and vessels, as well as their connections to each other. The difference in the application of color Doppler is the insonation angle, which should be as small as possible to permit optimal visualization of  flow.
Figure 14: Flow velocity waveform across the tricuspid valve at 28 weeks of gestation (left).
(E-wave = early ventricular filling and A-wave = atrial ventricular filling).
In the abdominal plane, the position of the aorta and inferior vena cava are first checked as well as the correct connection of the vein to the right atrium. Pulsed Doppler sampling from the interior vena cava, the ductus venosus or the hepatic veins can be achieved in longitudinal planes. The next plane, the four-chamber view, is considered as the most important, since it allows an easy detection of numerous severe heart defects. Using color Doppler in an apical or basal approach, the diastolic perfusion across the atrioventricular valves can be assessed (Figure 14). The separate perfusion of both inflow tracts is characteristic. The sampling of diastolic flow using pulsed Doppler will show the typical biphasic shape of diastolic flow velocity waveform with an early peak diastolic velocity (E) and a second peak during atrial contraction (A-wave). E is smaller than A and the E/A ratio increases during pregnancy toward 1, to be inversed after birth (Figure 15). In this plane, regurgitations of the atrioventricular valves, which are more frequent at the tricuspid valve, are easily detected during systole using color Doppler.
Figure 15: Ratio of early peak diastolic velocity (E) to second peak during atrial contraction (A-wave) across the mitral valve (left) and tricuspid valve (right) with gestation (mean, 95th and 5th centiles).
Flow across the foramen ovale is visualized in a lateral approach of the fourchamber-view. Color Doppler allows the confirmation of the physiological right–left shunt. Furthermore, careful examination of the left atrium allows the imaging of the correct connections of pulmonary veins entering the left atrium.
 

The transducer is then tilted to obtain, first, the five-chamber and then the short-axis view. Using color Doppler, flow during systole is visualized. In these planes, the correct ventriculo-arterial connections, the non-aliased flow and the continuity of the interventricular septum with the aortic root are checked. The sampling of flow velocity waveforms with pulsed Doppler will demonstrate, for the aortic and pulmonary valves, a single peak flow velocity waveform. The peak systolic velocity increases from 50 to 110 cm/s during the second half of gestation and is higher across the aortic than the pulmonary valve. Time to peak velocity in the aorta is longer than in the pulmonary trunk. The three-vessel view will enable the assessment of the aortic arch and the ductus arteriosus. In the last trimester of pregnancy, an aliased flow is found within the ductus as a sign of beginning constriction. In the case of optimal fetal position, the aortic and ductus arteriosus arch can be seen in a longitudinal plane, allowing the visualization of the neck vessels.

The parameters used to describe fetal cardiac velocity waveforms differ from those used in fetal peripheral vessels. Indices such as PI and resistance index, used for peripheral vessels, are derived from relative ratios between systolic, diastolic and mean velocity and are, therefore, independent of the absolute velocity values and from the angle of insonation between the Doppler beam and the direction of the blood flow 23. At the cardiac level, all the measurements represent absolute values. Measurements of absolute flow velocities require knowledge of the angle of insonation, which may be difficult to obtain with accuracy. The error in the estimation of the absolute velocity resulting from the uncertainty of angle measurement is strongly dependent on the magnitude of the angle itself. For angles less than about 20°, the error will be reduced to practical insignificance. For larger angles, the cosine term in the Doppler equation changes the small uncertainty in the measurement of the angle to a large error in velocity equations 23. As a consequence, recordings should be obtained always keeping the Doppler beam as parallel as possible to the bloodstream and all the recordings with an estimated angle greater than 20° should be rejected.

Color Doppler solves many of these problems because visualization of the direction of flow allows alignment of the Doppler beam in the direction of the blood flow.

To record velocity waveforms, pulsed Doppler is generally preferred to continuous wave Doppler because of its range resolution. During recordings, the sample volume is placed immediately distal to the locations being investigated (e.g. distal to the aortic semilunar valves to record the left ventricle outflow). However, in conditions of particularly high velocities (such as the ductus arteriosus), continuous Doppler may be useful because it avoids the aliasing effect.

 
Parameters measured

The parameters most commonly used to describe the cardiac velocity waveforms are 24:

(1) Peak velocity (PV), expressed as the maximum velocity at a given moment (such as systole or   diastole) on the Doppler spectrum;

(2) Time to peak velocity (TPV) or acceleration time, expressed by the time interval between the onset of the waveform and its peak;

(3) Time velocity integral (TVI), calculated by planimetering the area underneath the Doppler spectrum.

It is also possible to calculate absolute cardiac flow from both the atrioventricular valve and outflow tracts by multiplying TVI by the valve area and fetal heart rate. These measurements are particularly prone to errors, mainly due to inaccuracies in valve area. Area is derived from the valve diameter, which is near the limits of ultrasound resolution, and is then halved and squared in its calculation, thus amplifying potential errors. However, they can be used properly in longitudinal studies over a short period of time during which the valve dimensions are assumed to remain constant. Furthermore, it is also possible to accurately calculate the relative ratio between the right and left cardiac output (RCO/LCO) avoiding, the measurements of the cardiac valve, because, in the absence of cardiac defects, the relative dimensions of the aorta and pulmonary valves remain constant through gestation 25.

Evaluation of ventricular ejection force (VEF) has also been used to assess fetal cardiac function 26,27. This index estimates the energy transferred from right and left ventricular myocardial shortening to work done by accelerating blood into the pulmonary and systemic circulations, respectively 28. This index appears to be less influenced by changes in preload and afterload than other Doppler indices 28 and may be more accurate than other Doppler variables, such as peak velocities, for the assessment of ventricular function in adults with chronic congestive heart failure. VEF is calculated according to Newton’s second law of motion. The force developed by ventricular contraction, to accelerate a column of blood into the aorta or pulmonary artery, represents transfer of energy of myocardial shortening to work done on the pulmonary and systemic circulation. Newton’s second law estimates the force as the product of mass and acceleration. The mass component in this model is the mass of blood accelerated into the outflow tract over a time interval, and may be calculated as the product of the density of blood (1.055), the valve area and the flow velocity time integral during acceleration (FVI AT), which is the area under the Doppler spectrum envelope up to the time of peak velocity. The acceleration component of the equation is estimated as the PV divided by the TPV [VEF = (1.055 ´valve area´ FVI AT) ´ (PV/TPV)].

 
Doppler depiction of fetal cardiac circulation
 
In the human fetus, blood flow velocity waveforms can be recorded at all cardiac levels, including venous return, foramen ovale, atrioventricular valves, outflow tracts, pulmonary arteries and ductus arteriosus. The factors affecting the shape of the velocity waveforms include preload 29,30, afterload 30,31 , myocardial contractility 32, ventricular compliance 33 and fetal heart rate 34. These factors differ in their effect on waveforms recorded from different sites and parts of the cardiac cycle.
 
Atrioventricular valves
Flow velocity waveforms at the level of the mitral and tricuspid valves are recorded from the apical four-chamber view of the fetal heart and are characterized by two diastolic peaks, corresponding to early ventricular filling (E-wave) and to active ventricular filling during atrial contraction (A-wave) (Figure 14). The ratio between the E and A waves (E/A) is a widely accepted index of ventricular diastolic function and is an expression of both the cardiac compliance and preload conditions 24,29,35.
 
Outflow tracts
Flow velocity waveforms from the aorta and pulmonary arteries are recorded respectively from the five-chamber and short-axis views of the fetal heart (Figure 13). PV and TPV are the most commonly used indices. The former is influenced by several factors, including valve size, myocardial contractility and afterload 24,30,31, while the latter is believed to be secondary to the mean arterial pressure 36.
Figure 16: Five-chamber view of the fetal heart with superimposed color Doppler showing the aorta (blue) originating from the left ventricle (top). Short-axis view of the fetal heart with superimposed color Doppler showing the pulmonary artery originating from the right ventricle (bottom).
 
Coronary blood flow
Coronary blood flow may be visualized with the use of high-resolution ultrasound equipment and color Doppler echocardiography. In normal fetuses, both right and left coronary arteries may be identified after 31 weeks of gestation under optimal conditions of fetal imaging 37. In compromised fetuses, these vessels may be identified at an earlier gestational age, probably due to an increased coronary blood flow 37.
 
Pulmonary vessels
Velocity waveforms may be recorded from the right and left pulmonary arteries or from peripheral vessels within the lung 38–41. The morphology of the waveforms is different according to the site of sampling and there is a progressive increase in the diastolic component in the more distal vessels 40,41 (Figure 17). Their analysis may be used to study the normal development of lung circulation.
Figure 17a: Flow velocity waveform from the pulmonary artery at 32 weeks of gestation.
Figure 17b: Flow velocity waveform from the pulmonary vein at 32 weeks of gestation.
 
Ductus arteriosus
Ductal velocity waveforms are recorded from a short-axis view showing the ductal arch and are characterized by a continuous forward flow through the entire cardiac cycle 42. The parameter most commonly analyzed is the PV during systole or, similarly to peripheral vessels, the pulsatility index [PI = (systolic velocity - diastolic velocity)/ time averaged maximum velocity] 42,43.
 
Errors in Doppler blood flow velocity waveforms
 
A major concern in obtaining absolute measurements of velocities or flow is their reproducibility. To obtain reliable recordings, it is particularly important to minimize the angle of insonation, to verify in real-time and color flow imaging the correct position of the sample volume before and after each Doppler recording, and to limit the recordings to periods of fetal rest and apnea, as behavioral states greatly influence therecordings 44,45. In these conditions, it is necessary to select a series of at least five consecutive velocity waveforms characterized by uniform morphology and high signal to noise ratio before performing the measurements. Using this technique of recording and analysis, it is possible to achieve a coefficient of variation below 10% for all the echocardiographic indices with the exception of those needing the valve dimensions 46–48.
 
Normal ranges of Doppler echocardiographic indices
 
It is possible to record cardiac flow velocity waveforms from as early as 8 weeks of gestation by transvaginal color Doppler 49,50. In early pregnancy (8–20 weeks), there are major changes at all cardiac levels. The E/A ratio at both atrioventricular levels increases 49–51. PV and TVI in outflow tracts increase and this is particularly evident at the level of the pulmonary valve 49. These changes suggest a rapid development of ventricular compliance and a shift of cardiac output towards the right ventricle; this shift is probably secondary to decreased right ventricle afterload which, in turn, is due to the fall in placental resistance.

At the level of the atrioventricular valves, the E/A ratios increase 52,53, while PV values linearly increase at the level of both pulmonary and aortic valves 54. Small changes are present in TPV values during gestation 55. TPV values at the level of the pulmonary valve are lower than at aortic level, suggesting a slightly higher blood pressure in the pulmonary artery than in the ascending aorta 56. Quantitative measurements have shown that the right cardiac output (RCO) is higher than the left cardiac output (LCO) and that, from 20 weeks onwards, the RCO to LCO ratio remains constant, with a mean value of 1.3 57,58. This value is lower than that reported in fetal sheep (RCO/LCO = 1.8), and this difference may be explained by the higher brain weight in humans which necessitates an increase in left cardiac output 59.

In normal fetuses, VEF exponentially increases with advancing gestation, both at the level of the right and left ventricles 27. No significant differences are present between right and left VEF values and the ratio between right and left VEF values remains stable with advancing gestation (mean value = 1.09) 27.

Ductal PV increases linearly with gestation and its values represent the highest velocity in the fetal circulation occurring in normal conditions while the PI is constant 42,43. Values of systolic velocity above 140 cm/s, in conjunction with a diastolic velocity greater than 35 cm/s or a PI of less than 1.9, are considered to be an expression of ductal constriction 42.
Figure 18: Sagittal view of the fetal thorax and abdomen showing the ductus venosus originating from the umbilical vein , inferior vena cava and descending aorta.
(Color Doppler - Amplitude Mode)
 
FETAL VENOUS FLOW
 
Anatomy

The fetal liver with its venous vasculature – umbilical and portal veins, ductus venosus and hepatic veins – and the inferior vena cava are the main areas of interest in the investigation of venous blood return to the fetal heart. The intra-abdominal part of the umbilical vein ascends relatively steeply from the cord insertion in the inferior part of the falciform ligament. Then the vessel continues in a more horizontal and posterior direction and turns to the right to the confluence with the transverse part of the left portal vein, which joins the right portal vein with its division into an anterior and a posterior branch.

The ductus venosus originates from the umbilical vein before it turns to the right (Figure 18). The diameter of the ductus venosus measures approximately one-third of that of the umbilical vein. It courses posteriorly and in a cephalad direction, with increasing steepness in the same sagittal plane as the original direction of the umbilical vein, and enters the inferior vena cava in a venous vestibulum just below the diaphragm. The three (left, middle, and right) hepatic veins reach the inferior vena cava in the same funnel-like structure 60.

 
Figure 19: Parasagittal view of the fetal trunk with superimposed color Doppler showing the descending aorta (red) and the inferior vena cava (blue).
 
The ductus venosus can be visualized in its full length in a mid-sagittal longitudinal section of the fetal trunk (Figure 15). In an oblique transverse section through the upper abdomen, its origin from the umbilical vein can be found where color Doppler indicates high velocities compared to the umbilical vein, and sometimes this produces an aliasing effect (Figure 15). The blood flow velocity accelerates due to the narrow lumen of the ductus venosus, the maximum inner width of the narrowest portion being 2 mm 61. The best ultrasound plane to depict the inferior vena cava is a longitudinal or coronal one, where it runs anterior, to the right of and nearly parallel to the descending aorta (Figure 16). The hepatic veins can be visualized, either in a transverse section through the upper abdomen or in a sagittal-coronal section through the appropriate lobe of the liver.
 
Physiology
 

The ductus venosus plays a central role in the return of venous blood from the placenta. Well-oxygenated blood flows via this shunt directly towards the heart. Approximately 40% of umbilical vein blood enters the ductus venosus and accounts for 98% of blood flow through the ductus venosus, because portal blood is directed almost exclusively to the right lobe of the liver 62. Oxygen saturation is higher in the left hepatic vein compared to the right hepatic vein. This is due to the fact that the left lobe of the liver is supplied by branches from the umbilical vein.

Animal studies have shown that there is a streamlining of blood flow within the thoracic inferior vena cava 63. Blood from the ductus venosus and the left hepatic vein flows in the dorsal and leftward part, whereas blood from the distal inferior vena cava and the right lobe of the liver flows in the ventral and rightward part of the inferior vena cava. The ventral and rightward stream, together with blood from the superior vena cava, is directed towards the right atrium and through the tricuspid valve into the right ventricle. From there the blood is ejected into the main pulmonary artery and most of it is shunted through the ductus arteriosus into the descending aorta. The dorsal and leftward stream is directed towards the foramen ovale, thereby delivering well-oxygenated blood directly to the left heart and from there via the ascending aorta to the myocardium and the brain. In sheep, the two bloodstreams show different flow velocities, with the higher velocity found in the stream that originates from the ductus venosus 64. Color Doppler studies in human fetuses confirm these findings. The crista dividens, which forms the upper edge of the foramen ovale, separates the two pathways, and the blood delivered to the left atrium circumvents the right atrium 65.

The typical waveform for blood flow in venous vessels consists of three phases (Figure 20). The highest pressure gradient between the venous vessels and the right atrium occurs during ventricular systole (S), which results in the highest blood flow velocities towards the fetal heart during that part of the cardiac cycle. Early diastole (D), with the opening of the atrioventricular valves and passive early filling of the ventricles (E-wave of the biphasic atrioventricular flow waveform), is associated with a second peak of forward flow. The nadir of flow velocities coincides with atrial contraction (a) during late diastole (A-wave of the atrioventricular flow waveform). During atrial contraction, the foramen ovale flap and the crista dividens meet, thereby preventing direct blood flow from the ductus venosus to the left atrium during that short period of closure of the foramen ovale.

Figure 20: Normal flow velocity waveforms of the ductus venosus visualized in a sagittal section through the fetal abdomen. The first peak indicates systole, the second early diastole and the nadir of the waveform occurs during atrial contraction.
 
Normal Doppler findings - Venous Blood Flow

The easiest vessel in which to investigate venous blood flow is the umbilical vein. Investigation of fetal venous umbilical blood flow by Doppler ultrasound was published in 1980 by Eik-Nes and colleagues 66 and in 1981 by Gill et al.67. They reported on mean volume flow in the intra-abdominal part of the umbilical vein, which averaged 110–120 ml/kg/min in uncomplicated third-trimester pregnancies. Continuous forward flow without pulsations is seen in most pregnancies after the first trimester. It is interesting that there seems to be an intrinsic inhibition of retrograde flow in the umbilical vein. This was concluded from a study comparing flow volume and velocity measurements of test fluid pumped through the cord under standardized conditions in antegrade and retrograde directions 68. This was attributed to the orientation of the endothelial cells within the vessel wall.

In a study during early gestation, pulsations were always seen until 8 weeks and they progressively disappeared between 9 and 12 weeks 69. Other investigators observed them up to 15 weeks and no relation between the pulsatility of venous waveforms and the descending aorta and umbilical artery could be established 70. Changes in cardiac filling patterns were thought to be responsible for these findings. Other studies reported umbilical venous pulsations synchronous with the fetal heart rate in normal fetuses between 34 and 38 weeks 71. They were present in 20% of measurements in a freefloating loop of the cord, in 33% of intra-abdominal umbilical venous measurements, and in 78% of waveforms from the umbilical sinus and left portal vein. These mild pulsations and the sinusoidal waveforms occurring during fetal breathing movements must be distinguished from severe pulsations showing a sharp decrease in blood flow, corresponding to the fetal heart rate in cases of fetal compromise.

There is an abrupt change in the blood flow waveforms at the origin of the ductus venosus from continuous to pulsatile flow and an approximately three- to four-fold increase in maximum velocities. An abrupt pressure drop is present at the entrance of the ductus venosus and there is a high-velocity jet from the inlet throughout the lower portion of the ductus, with a decrease of velocities toward its outlet due to its conicity 72. Flow in the ductus venosus is directed toward the heart throughout the whole cycle. Even in early pregnancy, there is no retrograde flow during atrial contraction (Figure 21) 73. The high velocities probably support the preferential direction of blood flow towards the foramen ovale, and avoid mixing with blood with lower oxygen saturation from the inferior vena cava and right hepatic vein. The mean peak velocities increase from 65 cm/s at 18 weeks to 75 cm/s at term 61.

In contrast to the ductus venosus waveform, atrial contraction can cause absence or reversal of blood flow in the inferior vena cava and this is almost always the case in the hepatic veins (Figure 21 and 22).

 
Figure 21: Normal ductus venosus waveform at 12 weeks of gestation with positive flow during atrial contraction.
Figure 21(b): Normal ductus venosus waveform at 25 weeks of gestation with positive flow during atrial contraction.
Figure 22: Ductus venosus flow velocity waveform with low but positive forward flow during atrial contraction.
The percentage of reverse flow in the inferior vena cava decreases with advancing gestational age. At 12–15 weeks, it is four- to five-fold of that seen near term. Studies attempting to describe the pulsatility of flow velocity waveforms have used the S/D ratio in the inferior vena cava or ductus venosus 74–77, the preload index (a/S) in the inferior vena cava 78, and the resistance index [(S - a)/S] and the S/a ratio in the ductus venosus 79,80. With one exception 76, no significant change with gestational age has been found for the S/D ratio. Similarly, no relationship has been found between the preload index and gestational age, which is inconsistent with the finding of a decrease in percentage of reverse flow with advancing gestation 78. The ductus venosus index [(S - a)/S], which is equivalent to the resistance index, decreases significantly with gestational age 79. This is in agreement with a decrease of the S/a ratio with gestational age, which also shows a significant relationship with the percentage of reverse flow in the inferior vena cava 80.
Figure 23: Flow velocity waveform from the middle hepatic vein. Compared to the ductus venosus (see Figure 19), the velocities are significantly lower and there is reversal of blood flow during atrial contraction.
 
A study of blood flow in the ductus venosus, inferior vena cava and right hepatic vein in 143 normal fetuses during the second half of pregnancy established reference ranges for mean and maximum velocities and two indices for venous waveform analysis 81. The first one was the peak velocity index [(S - a)/D] and the second one the equivalent to the PI [(S - a)/time-averaged maximum velocity]. Mean and peak blood velocities increased, whereas the indices decreased with advancing gestation (Figure 21). Velocities were highest in the ductus venosus and lowest in the right hepatic vein, whereas the lowest indices were found in the ductus venosus and highest indices in the right hepatic vein. The finding that the degree of pulsatility decreases with gestation is consistent with a decrease in cardiac afterload due to a decrease in placental resistance, and may also reflect increased ventricular compliance and maturation of cardiac function. A decrease in end-diastolic ventricular pressure causes an increase in venous blood flow velocity towards the heart during atrial contraction.
 
Figure 24: PIV, which is the equivalent of pulsatility index (left) and mean blood velocity (right) in the ductus venosus with gestation (mean, 95th and 5th centiles).

The sampling site (Figure 25) is of crucial importance in venous Doppler studies. Velocities at the inlet of the ductus venosus, immediately above the umbilical vein, are higher than at the outlet into the inferior vena cava and the sampling site should be standardized at the inlet 82. There are relatively wide limits of agreement for intraobserver variation for velocity measurements. Inferior vena cava signals at the entrance to the right atrium show a large standard deviation for various waveform parameters 74. To avoid a mixture of overlapping signals from different bloodstreams, flow velocity waveforms from the inferior vena cava should be obtained more distally. The highest reproducibility of inferior vena cava waveforms is achieved by placing the sample volume between the entrance of the renal vein and the ductus venosus 83.

Figure 25: the sampling site of the ductus venousus (yellow circle).

Generally, flow volume measurements and absolute velocity measurements seem to have considerably higher inaccuracies and intra-patient variations compared to velocity ratios. This is due to problems caused by a high or unreliable angle of insonation and the fact that vessel diameter measurements are very vulnerable to errors. Ratios and indices of velocities, on the other hand, are to a large extent independent of the angle of insonation. Furthermore, fetal behavioral states have to be taken into account when measuring blood flow velocities in the ductus venosus. A 30% decrease of velocities was found during fetal behavioral state 1F compared to 2F, but no change in S/D ratio 84.

Waveforms of the ductus venosus with very little or even without pulsatility seem to be normal variants. They were found in 3% of measurements in a longitudinal study of normal pregnancies 82. There are conflicting reports on the existence of a sphincter regulating blood flow through the ductus venosus. Autonomous innervation may have an influence on ductal blood flow, but it is questionable whether there is an isolated muscular structure functioning as a sphincter. Apparent ductus venosus dilatation has been reported in two cases with growth-restricted fetuses, causing modifications of flow velocity waveforms with a reduction of velocities during atrial contraction and, consequently, an increase in pulsatility 85. These findings were confirmed in a simulation of ductal dilatation by means of a mathematical model.

During Doppler studies of the fetal circulation, it is essential to avoid measurements during fetal breathing movements. This is well described for the arterial side but it is even more important for venous flow, because the changes in intrathoracic pressure during breathing movements have a profound influence on flow velocity waveforms. A raised abdomino–thoracic pressure gradient seems to be responsible for this phenomenon. By applying the Bernoulli equation, the pressure gradient across the ductus venosus ranges between 0 and 3 mmHg during the heart cycle, but increases to 22 mmHg during fetal inspiratory movements 86. As the shape of velocity waveforms during breathing movements shows persistent changes, velocity ratios or indices should only be calculated during fetal apnea.

On the other hand, comparison between umbilical arterial and venous waveforms during fetal breathing movements offers an interesting model to investigate the interdependence between fetal cardiovascular and placental blood flow 87. Variation in umbilical venous velocity may alter placental filling and thereby affect umbilical arterial diastolic velocity. It may also alter ventricular filling and thereby affect umbilical arterial systolic velocity through the Frank–Starling mechanism, which results in limited changes in stroke volume. Therefore, changes in velocity of venous blood flow returning to the heart have an influence on velocities of arterial blood flow returning to the placenta and vice versa . In other words, cardiac preload influences afterload and is influenced by afterload itself.

Recent studies have investigated the venous circulation of the fetal brain and various sinuses 88,89. The increase of flow velocities and decrease of pulsatility with gestational age and the increase of the pulsatility of waveforms from the periphery toward the proximal portion of the venous vasculature is in accordance with findings in precardial venous vessels.

 
REERENCES

1. Giles WB, Trudinger BJ, Paimer AA. Umbilical cord whole blood viscosity and the umbilical artery flow velocity time waveforms: a correlation. Br J Obstet Gynaecol 1986;93:466

2. Boyd JD, Hamilton WJ. The Human Placenta. Cambridge: Heffer & Sons, 1970:207–74

3. Ramsey EM, CornerGW, DonnerMW. Serial and cineradioangiographic visualization of maternal circulation in the primate (hemochorial) placenta. Am J Obstet Gynecol 1963;86:213–25

4. Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 1967;93:569–79

5. Pijnenborg R, Bland JM, Robertson WB, Brosens I. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta 1983;4:387–414

6. Assali NS, Rauramo L, Peltonen T. Measurement of uterine blood flow and uterine metabolism. VIII. Uterine and fetal blood flow and oxygen consumption in early human pregnancy. Am J Obstet Gynecol 1960;79:86–98

7. Browne JCM, Veall N. The maternal placental blood flow in normotensive and hypertensive women. J Obstet Gynaecol Br Empire 1953;60:141–7

8. Campbell S, Diaz-Recasens J, Griffin DR, Cohen-Overbeek TE, Pearce JM, Willson K, Teague MJ. New Doppler technique for assessing uteroplacental blood inflow. Lancet 1983;i:675–7

9. Trudinger BJ,Giles WB, Cook CM. Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy. Br J Obstet Gynaecol 1985;92:39–45

10. Schulman H, Fleischer A, Farmakides G, Bracero L, Rochelson B, Grunfeld L. Development of  uterine artery compliance in pregnancy as detected by Doppler ultrasound. Am J Obstet Gynecol 1986;155:1031–6

11. Bewley S, Campbell S, Cooper D. Uteroplacental Doppler flow velocity waveforms in the second trimester. A complex circulation. Br J Obstet Gynaecol 1989;96:1040–6

12. Arduini D, Rizzo G, Boccolini MR, Romanini C, Mancuso S. Functional assessment of uteroplacental and fetal circulations by means of color Doppler ultrasonography. J Ultrasound Med 1990;9: 249–53

13. Maulik D, Yarlagadda P, Downing G. Doppler velocimetry in obstetrics. Obstet Gynecol Clin North Am 1990;17:163–86

14. Maulik D. Basic principles of Doppler ultrasound as applied in obstetrics. Clin Obstet Gynecol  1989;32:628–44

15. Bilardo CM, Campbell S, Nicolaides KH. Mean blood velocities and flow impedance in the fetal descending thoracic aortic and common carotid artery in normal pregnancy. Early Hum Dev 1988; 18:213–21

16. Vyas S, Nicolaides KH, Campbell S. Renal artery flow-velocity waveforms in normal and hypoxemic fetuses. Am J Obstet Gynecol 1989;161:168–72

17. Hecher K, Spernol R, Szalay S. Doppler blood flow velocity waveforms in the fetal renal artery. Arch Gynecol Obstet 1989;246:133–7

18. Rabinowitz R, Peters MT, Vyas S, Campbell S, Nicolaides KH. Measurement of fetal urine production in normal pregnancy by real-time ultrasonography. Am J Obstet Gynecol 1989;161:1264–6

19. Vyas S, Campbell S, Bower S, Nicolaides KH. Maternal abdominal pressure alters fetal cerebral blood flow. Br J Obstet Gynaecol 1990;97:740–2

20. Kirkinen P, Muller R, Huch R, Huch A. Blood flow velocity waveforms in human fetal intracranial arteries. Obstet Gynecol 1987,70:617–21

21. van den Wiingaard JAGW, Groenenberg IAL, Wiadimiroff JW, Hop WCJ. Cerebral Doppler ultrasound in the human fetus. Br J Obstet Gynaecol 1989;96:845–9

22. Vyas S, Nicolaides KH, Bower S, Campbell S. Middle cerebral artery flow velocity waveforms in fetal hypoxaemia. Br J Obstet Gynaecol 1990;97:797–803

23. Burns PN. Doppler flow estimations in the fetal and maternal circulations: principles, techniques and some limitations. In Maulik D, McNellis D, eds. Doppler Ultrasound Measurement of Maternal-Fetal Hemodynamics. Ithaca, New York, USA: Perinatology Press, 1987:43–78

24. Rizzo G, Arduini D, Romanini C. Doppler echocardiographic assessment of fetal cardiac function. Ultrasound Obstet Gynecol 1992;2:434–45

25. Comstock CH, Riggs T, LeeW, Kirk J. Pulmonary to aorta diameter ratio in the normal and abnormal fetal heart. Am J Obstet Gynecol 1991;165:1038–43

26. St John Sutton M, Gill T, Plappert T, Saltzman DH, Doubilet P. Assessment of right and left ventricular function in term of force development with gestational age in the normal human fetus. Br Heart J 1991,61:285–9

27. Rizzo G, Capponi A, Rinaldo D, Arduini D, Romanini C. Ventricular ejection force in growthretarded fetuses. Ultrasound Obstet Gynecol 1995;5:247–52

28. Isaaz K, Ethevenot G, Admant P, Brembilla B, Pernot C. A new Doppler method of assessing left ventricular ejection force in chronic congestive heart failure. Am J Cardiol 1989; 64:81–7

29. Stottard MF, Pearson AC, Kern MJ, Ratcliff J, Mrosek DG, Labovitz AJ. Influence of alteration in preload of left ventricular diastolic filling as assessed by Doppler echocardiography in humans. Circulation 1989;79:1226–36

30. Gardin JM. Doppler measurements of aortic blood velocity and acceleration: load-independent indexes of left ventricular performance. Am J Cardiol 1989;64:935–6

31. Bedotto JB, Eichorn EJ, Grayburn PA. Effects of left ventricular preload and afterload on ascending aortic blood velocity and acceleration in coronaric artery disease. Am J Cardiol 1989:64:856–9

32. Brownwall E, Ross J, Sonnenblick EH. Mechanism of Contraction in the Normal and Failing Heart, 2nd edn. Boston: Little Brown, 1976, 92–129

33. Takaneka K, Dabestani A, Gardin JM, Russel D, Clark S, Allfie A, Henry WL. Left ventricular filling in hypertrophic cardiomyopathy: a pulsed Doppler echocardiographic study. J Am Coll Cardiol 1986;7:1263–71

34. Kenny J, Plappert T, Doubilet P, Saltzam D, St John Sutton MG. Effects of heart rate on ventricular size, stroke volume and output in the normal human fetus: a prospective Doppler echocardiographic study. Circulation 1987;76:52–8

35. Labovitz AJ, Pearson C. Evaluation of left ventricular diastolic function: clinical relevance and recent Doppler echocardiographic insights. Am Heart J 1987;114:836–51

36. Kitabatake A, Inoue M, Asao M, et al. Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique. Circulation 1983;68:302–9

37. Baschat AA, Gembruch U, Reiss I, Gortner L, Diedrich K. Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to arterial and venous flow velocity waveforms and perinatal outcome. The heart sparing effect. Ultrasound Obstet Gynecol 1997;9:162–72

38. Laudy JAM, De Riddler MA, Wladimiroff J. Doppler velocimetry in branch pulmonary arteries of normal human fetuses during the second half of pregnancy. Pediatr Res 1997;41:897–901

39. Rasanen J, Huhta JC,Weiner S,Wood DC, Ludormisky A. Fetal branch pulmonary arterial vascular impedance during the second half of pregnancy. Am J Obstet Gynecol 1996;174:1441–9

40. Rizzo G, Capponi A, Chaoui R, Taddei F, Arduini D, Romanini C. Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses. Ultrasound Obstet Gynecol 1996;8:87–92

41. Chaoui R, Taddei F, Rizzo G, Bast C, Lenz F, Bollmann R. Doppler echocardiography of the main stems of the pulmonary arteries in the normal human fetus. Ultrasound Obstet Gynecol 1998;11: 173–9

42. Huhta JC, Moise KJ, Fisher DJ, Sharif DF,Wasserstrum N, Martin C. Detection and quantitation of constriction of the fetal ductus arteriosus by Doppler echocardiography. Circulation 1987;75, 406–12

43. Van de Mooren K, Barendregt LG, Wladimiroff J. Flow velocity waveforms in the human fetal ductus arteriosus during the normal second trimester of pregnancy. Pediatr Res 1991;30:487–90

44. Rizzo G, Arduini D, Valensise H, Romanini C. Effects of behavioural states on cardiac output in the healthy human fetus at 36–38 weeks of gestation. Early Hum Dev 1990;23:109–15

45. Huisman TW, Brezinka C, Stewart PA, StijenT, Wladimiroff JW. Ductus venosus flow velocity waveforms in relation to fetal behavioural states. Br J Obstet Gynaecol 1994;101:220–4

46. Groenenberg IAL, Hop WCJ, Wladimiroff JW. Doppler flow velocity waveforms in the fetal cardiac outflow tract; reproducibility of waveformrecording and analysis. Ultrasound Med Biol 1991; 17:583–7

47. Al-GhazaliW, Chita SK, Chapman MG, Allan LD. Evidence of redistribution of cardiac output in asymmetrical growth retardation. Br J Obstet Gynaecol 1989; 96:697–704

48. Reed KL, Meijboom EJ, Sahn DJ, Scagnelli SA, Valdes-Cruz LM, Skenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986;73:41–56

49. Rizzo G, Arduini D, Romanini C. Fetal cardiac and extra-cardiac circulation in early gestation. J Maternal-Fetal Invest 1991;1:73–8

50. van Splunder P, Stijnen T, Wladimiroff JW. Fetal atrioventricular flow-velocity waveforms and their relationship to arterial and venous flow velocity waveforms at 8 to 20 weeks of gestation. Circulation 1996;94:1372–8

51. Wladimiroff JW, HuismanTWA, Stewart PA, Stijnen Th. Normal fetal Doppler inferior vena cava, transtricuspid and umbilical artery flow velocity waveforms between 11 and 16 weeks’ gestation. Am J Obstet Gynecol 1992;166:46–9

52. Reed KL, Sahn DJ, Scagnelli S, Anderson CF, Shenker L. Doppler echocardiographic studies of diastolic function in the human fetal heart: changes during gestation. J Am Coll Cardiol 1986;8: 391–5

53. Rizzo G, Arduini D, Romanini C, Mancuso S. Doppler echocardiographic assessment of atrioventricular velocity waveforms in normal and small for gestational age fetuses. Br J Obstet Gynaecol 1988;95:65–9

54. Kenny JF, Plappert T, Saltzman DH, Cartire M, Zollars L, Leatherman GF, St John Sutton MG. Changes in intracardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fetus: a prospective Doppler echocardiographic study. Circulation 1986;74:1208–16

55. Rizzo G, Arduini D, Romanini C, Mancuso S. Doppler echocardiographic evaluation of time to peak velocity in the aorta and pulmonary artery of small for gestational age fetuses. Br J Obstet Gynaecol 1990;97:603–7

56. Machado MVL, Chita SC, Allan LD. Acceleration time in the aorta and pulmonary artery measured by Doppler echocardiography in the midtrimester normal human fetus. Br Heart J 1987;58:15–18

57. Allan LD, Chita SK, Al-GhazaliW, Crawford DC, Tynan M. Doppler echocardiographic evaluation of the normal human fetal heart. Br Heart J 1987;57:528–33

58. De Smedt MCH, Visser GHA, Meijboom EJ. Fetal cardiac output estimated by Doppler echocardiography during mid- and late gestation. Am J Cardiol 1987;60:338–42

59. Rizzo G, Arduini D. Cardiac output in anencephalic fetuses. Gynecol Obstet Invest 1991;32:33–5 60. HuismanTWA, Gittenberger-De Groot AC, Wladimiroff JW. Recognition of a fetal subdiaphragmatic venous vestibulum essential for fetal venous Doppler assessment. Pediatr Res 1992;32:338–41

61. Kiserud T, Eik-Nes SH, Blaas HGK, Hellevik LR. Ultrasonographic velocimetry of the fetal ductus venosus. Lancet 1991;338:1412–14

62. Edelstone DI, Rudolph AM, Heymann MA. Liver and ductus venosus blood flows in fetal lambs in utero. Circ Res 1978;42:426–33

63. Edelstone DI, Rudolph AM. Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs. Am J Physiol 1979;237:H724–9

64. Schmidt KG, Silverman NH, Rudolph AM. Assessment of flow events at the ductus venosus–inferior vena cava junction and at the foramen ovale in fetal sheep by use of multimodal ultrasound. Circulation 1996;93:826–33

65. Kiserud T, Eik-Nes SH, Blaas HG, Hellevik LR. Foramen ovale: an ultrasonographic study of its relation to the inferior vena cava, ductus venosus and hepatic veins. Ultrasound Obstet Gynecol 1992;2:389–96

66. Eik-Nes SH, Brubakk AO, Ulstein MK. Measurement of human fetal blood flow. Br Med J 1980; 280:283–4

67. Gill RW, Trudinger BJ, Garrett WJ, Kossoff G,Warren, PS. Fetal umbilical venous flow measured in utero by pulsed Doppler and B-mode ultrasound. I. Normal pregnancies. Am J Obstet Gynecol 1981;139:720–5

68. Potter PL. In vitro demonstration of inhibition of retrograde flow in the human umbilical vein. Ultrasound Obstet Gynecol 1997;9:319–23

69. Rizzo G, Arduini D, Romanini C. Umbilical vein pulsations: a physiologic finding in early gestation. Am J Obstet Gynecol 1992;167:675–7

70. van Splunder P, Huisman TWA, de Ridder MAJ, Wladimiroff JW. Fetal venous and arterial flow velocity wave forms between eight and twenty weeks of gestation. Pediatr Res 1996;40:158–62

71. van Splunder IP, Huisman TWA, Stijnen T, Wladimiroff JW. Presence of pulsations and reproducibility of waveform recording in the umbilical and left portal vein in normal pregnancies. Ultrasound Obstet Gynecol 1994;4:49–53

72. Pennati G, Bellotti M, Ferrazzi E, Rigano S, Garberi A. Hemodynamic changes across the human ductus venosus: a comparison between clinical findings and mathematical calculations. Ultrasound Obstet Gynecol 1997;9:383–91

73. Huisman TWA, Stewart PA, Wladimiroff JW, Stijnen T. Flow velocity waveforms in the ductus venosus, umbilical vein and inferior vena cava in normal human fetuses at 12–15 weeks of gestation. Ultrasound Med Biol 1993;19:441–5

74. Huisman TWA, Stewart PA, Wladimiroff JW. Flow velocity waveforms in the fetal inferior vena cava during the second half of normal pregnancy. Ultrasound Med Biol 1991;17:679–82

75. Huisman TWA, Stewart PA, Wladimiroff JW. Ductus venosus blood flow velocity waveforms in the human fetus – a Doppler study. Ultrasound Med Biol 1992;18:33–7

76. Reed KL, Appleton CP, Anderson CF, Shenker L, Sahn DJ. Doppler studies of vena cava flows in human fetuses. Insights into normal and abnormal cardiac physiology. Circulation 1990;81:498–505

77. Rizzo G, Arduini D, Romanini C. Inferior vena cava flow velocity waveforms in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 1992;166:1271–80

78. Kanzaki T, Chiba Y. Evaluation of the preload condition of the fetus by inferior vena caval blood flow pattern. Fetal Diagn Ther 1990;5:168–74

79. DeVore GR, Horenstein J. Ductus venosus index: a method for evaluating right ventricular preload in the second-trimester fetus. Ultrasound Obstet Gynecol 1993;3:338–42

80. Rizzo G, Capponi A, Arduini D, Romanini C. Ductus venosus velocity waveforms in appropriate and small for gestational age fetuses. Early Hum Dev 1994;39:15–26

81. Hecher K, Campbell S, Snijders R, Nicolaides K. Reference ranges for fetal venous and atrioventricular blood flow parameters. Ultrasound Obstet Gynecol 1994;4:381–90

82. Kiserud T, Eik-Nes SH, Hellevik LR, Blaas HG. Ductus venosus – a longitudinal Doppler velocimetric study of the human fetus. J Matern Fetal Invest 1992;2:5–11

83. Rizzo G, Arduini D, Caforio L, Romanini C. Effects of sampling sites on inferior vena cava f low velocity waveforms. J Matern Fetal Invest 1992;2:153–6

84. HuismanTWA, Brezinka C, Stewart PA, Stijnen T, Wladimiroff JW. Ductus venosus flow velocity waveforms in relation to fetal behavioural states. Br J Obstet Gynaecol 1994;101: 20–4

85. Bellotti M, Pennati G, Pardi G, Fumero R. Dilatation of the ductus venosus in human fetuses: ultrasonographic evidence and mathematical modeling. Am J Physiol 1998; 275:H1759–67

86. Kiserud T, Hellevik LR, Eik-Nes SH, Angelsen BAJ, Blaas HG. Estimation of the pressure gradient across the fetal ductus venosus based on Doppler velocimetry. Ultrasound Med Biol 1994;20:225–32

87. Indik J, Reed KL. Variation and correlation in human fetal umbilical Doppler velocities with fetal breathing: evidence of the cardiac–placental connection. Am J Obstet Gynecol 1990;163:1792–6

88. Laurichesse-Delmas H, Grimaud O, Moscoso G, Ville Y. Color Doppler study of the venous circulation in the fetal brain and hemodynamic study of the cerebral transverse sinus. Ultrasound Obstet Gynecol 1999;13:34–42

89. Pooh RK, Pooh KH, Nakagawa Y, Maeda K, Fukui R, Aono T. Transvaginal Doppler assessment of fetal intracranial venous flow. Obstet Gynecol 1999;93:697–701

Doppler in Obstetrics
Copyright © 2002 by Kypros Nicolaides, Giuseppe Rizzo, Kurt Hecker and Renato Ximenes
produced at Centrus ®