Ultrasound in Med. & Biol., Vol. 41, No. 5, pp. 1311–1319, 2015
Copyright Ó 2015 World Federation for Ultrasound in Medicine & Biology
Printed in the USA. All rights reserved
0301-5629/$ - see front matter

http://dx.doi.org/10.1016/j.ultrasmedbio.2014.12.008

d Original Contribution

MEASUREMENT OF INTERNAL DIAMETER CHANGES AND PULSEWAVE VELOCITY IN FETAL DESCENDING AORTA USING THE ULTRASONICPHASED-TRACKING METHOD IN NORMAL AND GROWTH-RESTRICTED
FETUSESSUSUMU MIYASHITA,*y JUN MUROTSUKI,*y JIN MUROMOTO,*y KATSUSUKE OZAWA,*yNOBUO YAEGASHI,z HIDEYUKI HASEGAWA,x and HIROSHI KANAIx* Department of Advanced Fetal and Developmental Medicine, Tohoku University Graduate School of Medicine, Sendai,
Miyagi, Japan; y Department of Maternal and Fetal Medicine, Miyagi Children’s Hospital, Sendai, Miyagi, Japan; z Departmentof Obstetrics and Gynecology, Tohoku University, Sendai, Miyagi, Japan; and x Department of Electronic Engineering, Tohoku
University Graduate School of Engineering, Sendai, Miyagi, Japan(Received 21 January 2014; revised 7 December 2014; in final form 11 December 2014)

Abstract—Phased tracking (PT) is an ultrasound-based technique that enables precise measurement of a target
velocity. The aims of this study were to use PT to evaluate arterial pulse waveform, pulse wave velocity and fetal
pulse pressure in normal and growth-restricted fetuses. One hundred fetuses with normal development and 15 fetuses with growth restriction were analyzed. Ultrasonic raw radiofrequency signals were captured from a direction
perpendicular to the vascular axis at the fetal diaphragmatic level for the difference in internal dimensions (DID),
or simultaneously from different directions for the pulse wave velocity. Pulsatile movement of the proximal anddistal intima of the vessels was analyzed using PT. The fetal DID exhibited no significant changes in growthrestricted fetuses. Pulse wave velocity (3.8 ± 0.32 m/s vs. 2.2 ± 0.069 m/s, p , 0.001) and estimated pulse pressure(6.9 ± 0.90 kPa vs. 2.5 ± 0.18 kPa, p , 0.001) were significantly elevated in growth-restricted fetuses. Assessment of
DID and pulse wave velocity of the descending aorta using PT is a feasible, non-invasive approach to evaluation of
fetal hemodynamics. (E-mail: ssmu.miyashita@nifty.ne.jp) Ó 2015 World Federation for Ultrasound in Medicine & Biology.
Key Words: Phased-tracking method, Pulse wave velocity, Fetal pulse pressure, Fetal growth restriction.

Hokanson et al. (1970, 1972) developed a phaselocked echo-tracking system that enables the assessmentof arterial wall motion using phase-related tracking gates.
Several studies have employed a phase-locked echotracking system to examine fetal vascular pulsation(Gennser and Isberg 1987; Luterkort and Gennser 1987;
Mori et al. 2000; Sindberg Eriksen and Gennser 1984;
Stale et al. 1991; Struijk et al. 1992), and Fujita et al.
(2002) reported a linear relationship between the pressure
and internal diameter of the fetal descending aorta in an
animal model. Of note, a more recent echo-tracking system can measure arterial internal diameter changes within
one-sixteenth of the ultrasound wavelength used by an instrument (e.g., a precision of approximately 20 mm with atransmission frequency of 5 MHz) (Niki et al. 2002).
Struijk et al. (2013) published a study on assessment offetal pulse pressure using the echo-tracking system.
Kanai et al. (1996) developed another ultrasonictracking system called the phased-tracking (PT) method,

INTRODUCTION
Recent developments in high-resolution ultrasound systems have enabled the precise observation of fetal organs
at an early gestational age. However, the measurement ofvery small structures and their fine movements remains aformidable challenge, because of the various physicalproperties (e.g., transmitting ultrasonic frequency or
wavelength) that limit measurement accuracy. In particular, conventional diagnostic ultrasound systems have difficulty measuring small displacements less than the
wavelength; this has prevented examiners from measuring
the fine motion of objects such as the fetal vessel wall.

Address correspondence to: Susumu Miyashita, Miyagi Children’s Hospital, 4-3-17, Ochiai, Aoba borough, Sendai City, Miyagi,
Japan 989-3126. E-mail: ssmu.miyashita@nifty.ne.jp
Conflicts of interest: The authors have no conflicts of interest to
declare.
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which uses small phase differences in raw radiofrequency(RF) signals to obtain measurements. Accurate tracing
and a very high spatial resolution of 0.5 mm can beachieved when PT is used to evaluate fine movements.
Further, the simultaneous recording of RF signals fromdifferent beam directions would hypothetically allow
evaluation of fetal pulse wave velocity (PWV). However,to date, no study has evaluated fetal PWV while using PT.
Because these parameters allow the estimation of fetal
pulse pressure (PP), their accurate measurement is essential for understanding hemodynamic alterations, especially in compromised fetuses.
Recent study revealed histologic changes and deteriorated compliance in the arterial walls in growthrestricted fetuses of animal model (Dodson et al. 2013).
Here, the study aims were to evaluate fetal arterial pulse
waveform and PWV and to estimate fetal blood pressure
and changes in growth-restricted fetuses using PT.

Volume 41, Number 5, 2015

Table 1. Characteristics of the patients
Growthrestrictedfetusesp-value

Number of fetuses analyzed
100
15
Number of fetuses with available
data
Pulse waveform
97
15
Pulse wave velocity
65
15
Estimated fetal pulse pressure
54
15
Fetal age at measurement (wk)
27.5 6 6.3* 31.0 6 5.6Maternal age
30.1 6 4.6 30.3 6 5.4
Nulliparous
38
9
Maternal pre-eclampsia
00
Non-reassuring fetal status
00
Oligohydramnios
0
1
AEDV in umbilical artery01
CPR , 1
0
3

0.099
0.78
0.092
—
—
0.13
0.13
0.0018

Normalfetuses

AEDV 5absent end-diastolic velocity; CPR 5 cerebroplacental ratio
in the Doppler examination.
* Mean 6 standard deviation.

METHODS
Patients
One hundred fifteen women with singleton pregnancies were enrolled in this study. One hundred fetuses (16–40 wk of age) exhibited normal growth, and 15 (24–34 wk
of age) were growth restricted. Fetuses with apparent
fetal anomalies, including structural heart disease,arrhythmia, hydrops, macrosomia, multiple pregnancy,
chromosomal abnormalities and congenital infection
and fetuses of mothers with complications such as diabetes, anemia, drug abuse, alcoholic/smoking history, hypertension and significant heart/liver/renal disease were
excluded from the study. This study was approved by
the institutional ethics committee, and all measurements
were performed with written informed consent at the
Department of Maternal and Fetal Medicine of Miyagi
Children’s Hospital, Sendai City, Japan, from June 2010
to May 2013. A fetus was defined as growth restricted
when the Z-score of the estimated weight was equal toor less than 21.5 SD of the Japanese standard. No
repeated measurements were performed in any of thecases during the gestational period. Table 1 lists the characteristics of the patients.
Ultrasonic phased-tracking method
With the use of ultrasonic diagnostic equipment (Hitachi-ALOKA ProSound F75, Tokyo, Japan), the direction of the ultrasonic beam was fixed, and the received
RF signals were sampled at 20 MHz for several cardiac
cycles. Quadrature demodulation was applied to thesampled RF signals off-line. The principles underlying
PT, including theoretical and in vivo evaluations of themeasurements, have been described previously (Kanai
et al. 1996).

Radiofrequency pulses with an angular frequency ofu0 5 2pf0 (f0 5 5 MHz) are transmitted at time intervalsof DT. The phase difference, Dq(x; t), between the phaseq(x; t) of the quadrature-demodulated signal z(x; t) of thereceived signal, y(x; t), and the phase q(x; t 1 DT) of thequadrature-demodulated signal z(x; t 1 DT) of the subsequently received signal, y(x; t 1 DT), is given by
Dqðx; tÞ 5 qðx; t1DTÞ2qðx; tÞ 5 2

2u0$DxðtÞ
c0(1)

where Dx(t) 5 x(t 1 DT) 2 x(t) is the movement of theobject during the short period DT around time t, and c0
is the acoustic velocity in the soft tissue.
In the present study, DT was set at 2.38 ms. That is,
the frame rate was 421 Hz, so that the measurable velocity
was set at a fair limit of 0.32 m/s (at f0 5 5 MHz). By
dividing the movement Dx by the period DT, the averagevelocity v(t 1 DT/2) of the object during the period DT isgiven by


DT
DxðtÞ
c0 Dqðx; tÞ
5
(2)
v t1
$
5
2
DT
2u0 DT
The phase difference Dq(x; t) is accurately determined by the constrained least-squares approach basedon the complex cross-correlation between z(x; t) andz(x; t 1 DT) under the condition that signal waveforms
change only in phase values during DT. It is impossible
to accurately determine the true lag value from the complex correlation function, which is derived from the standard normalized mean squared difference between thequadrature-modulated signals of the successively
received signals (Sabbah et al. 1981). However, the introduction of the constraint is effective for determining theUS phased-tracking method in growth-restricted fetuses d S. MIYASHITA et al.

lag between these complex signals. By multiplying theresultant velocity v(t 1 DT/2) by DT, the next depthx(t 1 DT) of the object is estimated asDTDxðt1DTÞ 5 xðtÞ1v t1
$DT
(3)
2
With the estimated depth position x(t 1 DT), the position of the region of interest on the vessel wall is successfully tracked. The initial positions of the sampling
points on the vessel wall were manually set along the ultrasonic beam.
In this study, a high-speed analogue-to-digital converter with large-scale memory was employed to analyze
the complex signal resulting from the quadrature modulation of the signal received by a 5-MHz convex-type ultrasonic transducer connected to standard ultrasonicdiagnostic equipment. The lower limit of resolution ofvessel wall displacement was 0.5 mm, and the higher limitof measurable velocity was about 0.32 m/s, which was
determined by aliasing of the conventional Doppler
system.
Pulse waveforms of the dimensions of the descending
aorta
The fetal descending aorta was identified in the longitudinal direction on the transabdominal B-mode plane
using a 5-MHz convex matrix-array probe. RF signals
were captured for 2 to 4 s from an adjusted beam direction
perpendicular to the arterial axis at the level of the dia-1313

phragm (Fig. 1). PT was employed for off-line analysis
of pulsatile movement of the proximal or distal borderof the arterial lumen, which was assumed to be the intima
of the vessels, and the initial positions for tracking wereindicated manually using a mouse. The velocities of theproximal or distal border could be analyzed as primarydata, and the differential between these parameters
implied the velocity of the changes in internal dimensions, whereas the time integral of these parameters revealed changes in internal diameter. On the basis of thisanalysis, we evaluated the following parameters: Vs, themaximum velocity in the systolic phase; Vd, the minimum
velocity in the diastolic phase; Dmax, the maximum internal diameter in the systolic phase; and Dmin, the minimum
internal diameter in the diastolic phase. The difference ininternal dimensions (DID) was obtained from the differential between Dmax and Dmin. All measurements were
performed in resting fetuses; background fetal motion,such as breathing movements, were avoided. The averages of five cardiac cycles were analyzed. Figure 2 illustrates an example of the analyzed waves of a changing
velocity and the displacement of an internal diameter.

Pulse wave velocity
At the same setting used for measuring the dimensions of the descending aorta, RF signals were captured
simultaneously from different directions. PT was applied
to the proximal border of the lumen at different positionsin the descending aorta. A measuring point was set on theFig. 1. Analysis of pulse waveforms for the dimensions of the fetal descending aorta. (a) Each velocity of the proximaland distal border of the lumen was analyzed using the phased-tracking method (PT). (b) Differences between the two
waves in (a) were used to determine the velocity of the change in internal diameter. (c) The time integral of the wavein (b) yielded the change in internal diameter. (d) The direction of the beam transmission was set perpendicular to thearterial axis at the level of the diaphragm.

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Volume 41, Number 5, 2015

Fig. 2. Definitions of the parameters analyzed in this study. Vs 5 maximum velocity in systolic phase; Vd 5 minimum
velocity in diastolic phase; Dmax 5 maximum internal diameter in systolic phase; Dmin 5 minimum internal diameter indiastolic phase; DID 5 difference in internal dimensions.

upper side of the diaphragm, and another on the lower
side (Fig. 3). The velocities of the proximal borderwere analyzed at each position, and the time delay

between them was measured; the average of five cardiac
cycles was used for the analysis. PWV was obtained by
dividing the distance between the analyzed positions by
the time delay of the pulse wave. The time delay in thevelocity waves of the arterial wall was analyzed anddefined as the peak-to-peak interval in the systolic phase.
Estimation of fetal pulse pressure
In the Moens–Korteweg equation, PWV (m/s) is
given bysﬃﬃﬃﬃﬃﬃﬃﬃ
Eq h
(4)
PWV 5
rd
where Eq is the circumferential elastic modulus of thewall, h is the wall thickness, d is the internal diameterand r is the blood density. The elastic modulus was
defined as the ratio of circumferential wall stress to strain
and is given by
Eq 5

Fig. 3. Analysis of pulse wave velocity (PWV) for the fetal descending aorta. Radiofrequency signals were captured simultaneously from different directions. The velocity of the proximal
border of the lumen at different positions on the descending
aorta was analyzed with the phased-tracking method. PWV
was obtained by dividing the distance between the analyzed
points (D) by the delayed time (Dt) of the velocity wave.

stressðd=2hÞDp
d2
5
5
Dp
strain ðpðd1DdÞ2pdÞ=pd 2hDd

(5)where Dd is the difference in internal diameter, and Dp isthe PP. Substitution of Eq in (5) with (4) yieldssﬃﬃﬃﬃﬃﬃﬃﬃ sﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃﬃ
Eq h
dDp
5
PWV 5
rd
2rDd

(6)

US phased-tracking method in growth-restricted fetuses d S. MIYASHITA et al.

The PP (Dp [N/m2]) can be estimated as
Dp 5

2rDd
$PWV2
d

(7)

Statistical analysis
All measured data were analyzed using JMP 10.0.2(SAS, Cary, NC, USA, 2013) or R 2.6.2 (The R Foundation for Statistical Computing, 2012). Both linear andnon-linear regression analyses were applied to the building of regression models. Fisher’s exact test, the Mann–
Whitney U-test and two-way factorial analysis of variance (ANOVA) were employed to compare growthrestricted fetuses with normally growing fetuses throughgestation. We verified intra-observer variability with thecoefficient of variation (CV) and intra-class correlation
coefficient (ICC) of repeated measurements (68 cases
for pulse waveforms of dimensions and 53 cases for
PWV). There were only two ultrasound observers inthis study. Inter-observer variability was also examinedusing Bland–Altman analysis of alternate measurements
in two cases of normal development for 28 wk. Statisticalsignificance was set at p , 0.05.
RESULTS
Pulse waveforms of the dimensions of the descending
aorta
Data for 97 of the 100 normal fetuses and all of thegrowth-restricted fetuses were available for analysis; datafor 3 normal fetuses were excluded because of poor
recording. Analysis of the measurements by gestational
week is illustrated in Figure 4(a, b). Table 2 summarizes
the results of the regression analyses for each parameter
evaluated.
Pulse wave velocity
After the exclusion of data for 32 normal fetuses
because of poor recordings or missed measurements,
data for 65 normal fetuses and all growth-restricted fetuses were available for analysis. Fetal PWV by gestational week is illustrated in Figure 5 for the two study
groups. Results of regression analyses for the normal
and growth-restricted fetuses are summarized inTable 2. PWV of the descending aorta was significantly
higher in growth-restricted fetuses compared with normal
fetuses (mean 6 standard error: 3.8 6 0.32 m/s vs. 2.2 6
0.069 m/s, p , 0.001).
Estimated fetal pulse pressure
Measurements for 54 normal fetuses and all growthrestricted fetuses were available for estimating fetal PP(Fig. 6). It was possible to estimate fetal PP with eqn(7) using DID/Dmin and PWV when the blood density

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was set at 1.05 (Hinghofer-Szalkay and Greenleaf
1987). Estimated PP was significantly elevated in
growth-restricted fetuses (6.9 6 0.90 kPa vs. 2.5 6
0.18 kPa, p , 0.001).
Intra-observer and inter-observer variability
The CV, ICC and Bland–Altman analysis of measurements are summarized in Table 3. The CV was less than
10% overall for the parameters analyzed, and there wasno specific tendency toward a change in the evaluation
during the gestational period. Bland–Altman analysis
revealed no significant differences between observers.
DISCUSSION
Pulse waveforms of arterial dimensions
Ultrasonic PT, which has superior measurement accuracy compared with the phase-locked echo tracking
system (Hasegawa and Kanai 2006), was newly employed in the present study to measure pulse waveformsof arterial dimensions in the fetal period. Dmin and Dmax
increased linearly with gestational age; however, DID
had a negative squared correlation. DID exhibited a rapid
increase before 28 wk, but the rate of increase subsequently slowed until no further increase was observed,
suggesting an increase in cardiac stroke volume or PP occurs during the fetal period. Sugawara et al. (2000) reported a positive linear relationship between pulsepressure and the internal diameter of human arteries.
This previous finding indicates that the increases in
Dmin, Dmax and DID with gestational age reflect a developmental rise in systolic, diastolic and pulse pressures,
respectively. The CV and ICC in measurements arethought to be acceptable, as they seem to be on thesame level as those from Doppler examinations orspeckle tracking for fetal cardiovascular investigation(Mavrides et al 2001; Van Mieghem et al. 2010).
Bland–Altman analysis revealed no systematic interobserver errors in these measurements.
It has been recognized that both structural development and functional development of the myocardium
occur during the fetal and neonatal periods. In the fetal
myocardium, only relatively small numbers of sarcoplasmic reticuli, transverse tubules and mitochondria
are present, and only limited ATPase activity is observed(Brook et al. 1983; Ingwall et al. 1981; Nakanishi et al.
1986, 1987). Several studies have investigated calcium
channels in fetal cardiomyocytes, which provide
myocardial contractility (Nguemo et al. 2007; Wetzel
et al. 1993). L-Type Ca21 currents exhibit rapid
increases during the fetal period, especially during thefirst half (Masuda et al. 1995), that may explain theplateau in DID after 28 wk. However, few details of
increasing fetal arterial function are known; nonetheless,

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Volume 41, Number 5, 2015

Fig. 4. (a) Vd and Vs in relation to gestational week in normal and growth-restricted fetuses. The solid line represents theregression line, and the dotted lines indicate the 95% confidence interval. (b) Dmin, Dmax, DID and DID/Dmin in relation togestational week in normal and growth-restricted fetuses. The solid line represents the regression line, and the dotted lines
indicate the 95% confidence interval. FGR 5 fetal growth restriction; GW 5 gestational week.

this structural and functional development in the myocardium may explain the increases in blood pressure as
relating to Dmin, Dmax and DID of the arterial pulse waveform. After establishment of a developmental pattern for
Dmin, Dmax, DID and DID/Dmin in normally growing fetuses, we found no statistical differences between thetwo study groups in relation to these parameters, suggest-

ing minimal or concealed changes in internal diameteroccurred in the growth-restricted fetuses relative to thenormal fetuses during the fetal period.
Pulse wave velocity
Measurement of PWV is a well-established method
for the non-invasive evaluation of arterial stiffness afterUS phased-tracking method in growth-restricted fetuses d S. MIYASHITA et al.

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Table 2. Results of regression analysis for normally developing fetuses and two-way ANOVA for growth-restricted fetuses
Regression analysis
2

Two-way ANOVA: normal vs. FGR

Parameter

Estimated equationR

p-valuep-valueVd (mm/s)
Vs (mm/s)
Dmin (mm)Dmax (mm)DID (mm)
DID/DminPWV (m/s)
Estimated PP (kg m21 s22)

20.31 3 GW 1 0.074
0.65 3 GW 2 2.13
0.17 3 GW 2 1.25
0.20 3 GW 2 1.44
1.33 3 GW2 1 104 3 GW 2 1148
0.00005 3 GW 1 0.204
0.0018 3 GW 1 1.73
0.0025 3 GW 1 2.46

0.43
0.55
0.84
0.87
0.70
0.000030
0.00430.00015,0.001,0.001,0.001,0.001,0.001
0.76
0.098
0.93

0.42
0.60
0.73
0.98
0.20
0.13
,0.001,0.001ANOVA 5 analysis of variance; DID 5 difference in internal dimensions; FGR 5 fetal growth restriction; GW 5 gestational week; PP 5 pulsepressure; PWV 5 pulse wave velocity.

birth. Positive correlation of PWV with mean blood pressure was also reported in adult patients (Stewart et al.
2003). However, to date, only a few studies have attempted to measure fetal PWV. In the present study, we employed the phased-tracking method to measure fetal
local PWV in normal and growth-restricted fetuses.
Intra-observer and inter-observer reliabilities were
thought to be acceptable in this study (Table 3).
Traditionally, PWV has been measured at the time oftransit of the foot of the pressure or displacement wave
and not the peak derivative of pressure. The foot of thepressure wave is not affected by reflected waves, whichmakes the positions of the peaks in pressure and its derivative change with respect to the foot because of the backward moving waves; therefore, PWV changes during the
cardiac cycle and depends on diastolic pressure. However, in the present study, changes in the diameters of somewaves were difficult to measure because of the uncertainty of the bottom point of the fetal cardiac cycle. We
decided, instead, to use velocity waves with clear peaks.
The differences were thought to be small because themeasurement sites were close and the peak velocity
occurred very close to the foot of displacement and wasminimally affected by reflections. Five serial waves
were analyzed, and their average was employed in thisstudy. In all cases, five serial waves were almost thesame in its figure and time scale, and we could not pointout significant differences among the waves in the samecase. We thought it sufficient to measure velocity waves
to evaluate fetal PWV even though the systolic and diastolic phases could not be distinguished accurately.
Fetal PWV was typically around 2 m/s and exhibiteda slight elevation during the fetal period, which is lower
than the range of 4–8 m/s reported for healthy children
and young adults (Koivistoinen et al. 2007; Reusz et al.
2010), suggesting low arterial stiffness or low pulsepressure in the fetal period. In the present study,
elevated PWV was observed in growth-restricted fetuses,
which can likely be explained by the alteration of arterial
wall properties. Several studies have focused on the

structural remodeling of arterial walls in growthrestricted fetuses in animal models and human patients.
In particular, the elastin-versus-collagen ratio has beenreported to be a major determinant of arterial stiffness(O’Rourke et al. 2002), and increased collagen content
has been reported to provide a good measure of thedecrease in compliance of arterial walls (Dodson et al.
2013; Thompson et al. 2011). Further, Kinzler et al.
(2005) reported that the mRNA of collagen I and III
was increased in the cord blood of growth-restricted fetuses, and a negative relation between arterial stiffness
and birth weight has been observed (Cheung et al.
2004). However, there is no evidence of increased diastolic pressure in the fetal period, even in animal models
of growth restriction.
Various investigators have described a prenatal programming effect on blood pressure. Prenatal hyponutrition or hypoxia results in small numbers of nephrons,
which is a strong predictor of adult hypertension (Ritz
et al. 2011). Liao et al. (1999) reported that decreased
arterial stiffness is related to the development of hypertension in normotensive patients. Low birth weight is

Fig. 5. Pulse wave velocity in relation to gestational week innormal and growth-restricted fetuses. The solid line represents
the regression line, and the dotted lines indicate the 95% confidence interval. FGR 5 fetal growth restriction; GW 5 gestational wk; PWV 5 pulse wave velocity.

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Ultrasound in Medicine and Biology

Volume 41, Number 5, 2015aorta. The circumferential elastic modulus (Eq) was taken
into account in the Moens–Korteweg equation, but theradial and axial elastic moduli might be the causes of
non-linearity. The fetal descending aorta is bound firmly
on the dorsal side, which could have resulted in asymmetric wall motion and thereby affected PWV. In addition, estimated PP assumed a constant PWV, but PWVchanges during the cardiac cycle. Finally, the fetal bodyis inside the amniotic cavity. As such, it remains controversial whether intrauterine static pressure can be ignored
and whether blood pressure functions the same way as exutero.
The estimated PP was elevated in growth-restrictedfetuses in the present study. There was no clear evidence
of enlarged arteries in growth-restricted fetuses in thesame gestational week; therefore, estimated PP wasthought to represent fetal PP, but the absolute values
were nonetheless too high. However, estimated PP might
be used as an index of fetal PP and could be sufficient for
ontogenic evaluation. A future direction of this study will
be to use PWVand estimated PP to relate blood pressure tofetal compromise in, for example, structural heart diseases, arrhythmia and twin-to-twin transfusion syndrome.

Fig. 6. Estimated pulse pressure in relation to gestational week
in normal and growth-restricted fetuses. The solid line represents the regression line, and the dotted lines indicate the 95%
confidence interval. FGR 5 fetal growth restriction; GW 5
gestational wk; PP 5 pulse pressure.

reported to be associated with increased stiffness of large
arteries and reduced compliance and with increased
blood pressure in adult life (Martyn et al. 1995). Thus,
fetal PWV measurement may be helpful in the earlyrecognition of persons with a high risk of adult-onset hypertensive diseases.
Estimated pulse pressure
Struijk et al. (1992, 2013) reported on the estimationof fetal PP; however, an echo-tracking system was employed for measurements of the diameter of the descending aorta. In the present study, we could analyze data froma sufficient number of individuals with the superior measurement accuracy of PT. Nonetheless, the estimated PP
values were around 2.5 kPa (19 Torr), which seemed
too high, and the values varied widely in normal fetuses,
but were typically less than 5 kPa in most cases. These results indicate our estimation model is not appropriate andrequires further modification. Several reasons could account for the high values. A non-linear relationship between pressure and compliance can be assumed with avery low pressure range in an actual fetal descending

Study limitations
This study had several limitations. First, calibrationof blood pressure is quite difficult in fetuses. Second,
there was no conclusive proof of a linear relation between
pressure and internal diameter in the low pressure range
in fetuses during early gestation. Third, the initial points
at which to begin tracking on the arterial wall were set
manually in our system. Hence, the spatial resolution of
the initial internal diameter depended on the fundamental
transmission frequency in the B-mode of the ultrasoundinstrument. Also, the temporal resolution of 2.38 ms
was fair, but not quite sufficient for estimating PWV.
Finally, the method used to measure PWV differedfrom that commonly used in infants or adolescents
because arterial tonometry is almost impossible in the

Table 3. Intra- and inter-observer reliability of measurements in phased-tracking method
Bland–Altman analysis
Parameter
Vd
Vs
Dmin
Dmax
DID
PWV

Number ofpatients
68
68
69
69
56
53

Number ofmeasurements
340
340
345
345
280
265

Coefficient ofvariation (%)
y6.4 6 0.46
4.8 6 0.38
6.3 6 0.42
5.0 6 0.33
5.4 6 0.56
9.3 6 0.87

DID 5 difference in internal dimensions; PWV 5 pulse wave velocity.
* p-Value for significant difference in average of measurements.
yMean 6 standard error.

Intra-class correlation
coefficient

Pairs ofmeasurements

p-value*

0.90
0.93
0.95
0.96
0.95
0.95

74
74
74
74
74
58

0.58
0.48
0.79
0.80
0.39
0.91

US phased-tracking method in growth-restricted fetuses d S. MIYASHITA et al.

fetal period. In the future, improved spatial and temporal
resolution will enable direct measurement of foot-to-footof displacements, which will facilitate accurate measurements of PWV, especially for the small distance in tiny
fetuses.
CONCLUSIONSThe ultrasonic phased-tracking method was found to
be feasible for evaluating the dimensions and PWV of the
fetal descending aorta with fair accuracy. It was possible
to estimate fetal PP with the Moens–Korteweg equation,
but this estimation model was found to be incomplete andwill require further modifications to be suitable for fetuses.
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