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Correlation of the fetal cerebellar volume with other fetal growthindices by three-dimensional ultrasound
EDWARD ARAUJO JUNIOR, CLAUDIO RODRIGUES PIRES,
LUCIANO MARCONDES MACHADO NARDOZZA,
HELIO ANTONIO GUIMARAES FILHO, & ANTONIO FERNANDES MORON
Obstetrics Department, Sao Paulo Federal University (Unifesp/EPM), Sao Paulo, SP, Brazil
(Received 5 March 2007; revised 4 April 2007; accepted 4 April 2007)
Abstract
Objective. To verify the correlation of fetal cerebellar volume by three-dimensional ultrasound (3D US) with other indicesof fetal growth in normal fetuses.
Methods. This was a longitudinal prospective study involving 52 normal pregnant women between 20 and 32 weeks ofgestation. The assessments of the fetal cerebellar volume were carried out at intervals of two weeks, and the method used wasVOCAL (virtual organ computer-aided analysis) with a 308 rotation angle. At each assessment, the following biometricindices were evaluated using the two-dimensional method: biparietal diameter, head circumference, transverse cerebellardiameter, femur length, and estimated fetal weight. We used Pearson’s correlation coefficient to evaluate the correlationbetween fetal cerebellar volume and these indices; we also used polynomial regression analysis with fetal cerebellar volume asthe dependent variable and the other indices as the independent variable.
Results. The fetal cerebellar volume was highly correlated with gestational age (r¼ 0.94; p5 0.001) and with all other fetalgrowth indices (p5 0.001).
Conclusions. The assessment of the fetal cerebellar volume by 3D US is an important tool to evaluate fetal growth.
Keywords: Three-dimensional imaging, fetus, cerebellum, organ volume
Introduction
The cerebellum can be identified in an ultrasound
test by the end of the first trimester [1]; however,
early diagnosis of posterior fossa abnormalities
should be avoided before 18 weeks of gestation [2].
It is also well known that the characteristics (shape,
echogenicity) of the cerebellum change with increas-
ing gestational age [3].
The cerebellar volume seems to be the most
objective method for the detection of cerebellar
hypoplasia when evaluating cerebellar growth. The
cerebellum is a small organ with a unique shape, and
for this reason the measurement of its volume using
two-dimensional ultrasound (2D US), from the
product of its largest diameters with the constant
0.52, can lead to major mistakes [4].
In the last ten years, the development of three-
dimensional ultrasonography (3D US) has offered us
new options in the assessment of the volume of fetal
organs [5–8]. Its main advantage over 2D US is the
possibility of getting a global outline of the organ,
which theoretically enables a more accurate volu-
metric analysis, especially for structures with irregu-
lar outlines.
The first studies using 3D US in the evaluation of
the fetal cerebellum were published recently, both of
them on populations in Taiwan. 3D US was found to
be better than 2D US for measuring the cerebellar
transverse diameter (CTD) and the cerebellar
antero-posterior diameter (CAD), and was found
to be useful in the evaluation of cerebellar growth
and gestational age, and to detect anomalies [4].
In another study, the high correlation of fetal
cerebellar volume with growth indices was verified
[9]. However, we should stress the great ethnic
differences between the Brazilian population and the
population of Taiwan.
In the last five years, a new technique for volume
calculation with 3D US has been used – the VOCAL
Correspondence: Edward Araujo Junior, Antonio Borba Street, 192 apt. 43, Alto de Pinheiros, 05451-070 Sao Paulo – SP, Brazil.
Tel: þ55 11 3022 8538/þ55 11 9368 5430. Fax: þ55 11 3672 8114. E-mail: [email protected]
The Journal of Maternal-Fetal and Neonatal Medicine, August 2007; 20(8): 581–587
ISSN 1476-7058 print/ISSN 1476-4954 online � 2007 Informa UK Ltd.
DOI: 10.1080/14767050701482928
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method (virtual organ computer-aided analysis) –
which is an extension of the 3-D View program
(General Electric Medical Systems, Kretztechnik,
Zipf, Austria). An experimental study in vitro has
demonstrated that this technique is more sensitive
than the multiplanar technique for the volume
calculation of objects with irregular shape [10], and
its reproducibility has also been proven in vivo [11].
There a very few studies reported in the medical
literature on the use of 3D US for volume calculation
of the fetal cerebellum; what we do know is that
CTD varies in different ethnic groups at the same
gestational age [12]. Therefore, the objective of this
study was to evaluate the correlation of the fetal
cerebellar volume using of the Brazilian population
using 3D US with other fetal growth indices.
Methods
We carried out a longitudinal prospective study, with
normal pregnant women between 20 and 32 weeks of
gestation, from January to October 2005. The
patients were selected from the Ultrasound Training
Center of Sao Paulo (CETRUS), and all the parti-
cipant patients signed a consent form. The study was
approved by the ethics research committee of the
Federal University of Sao Paulo (Unifesp/EPM).
The inclusion criteria were: single gestation with
gestational age between 20 and 32 weeks; women
with known last menstruation period (LMP) and
gestational age confirmed by ultrasound before the
16th week; absence of maternal pathologies that
could interfere in fetal growth; and absence of fetal
malformations. Fifty-two pregnant women were
selected and the ultrasound evaluations were carried
out every two weeks. The patients were arbitrarily
subdivided into three groups (A, B, and C), and all
patients were first evaluated at 20 weeks of gestation.
Group A underwent subsequent evaluations at 22
and 28 weeks, group B at 24 and 30 weeks, and
group C at 26 and 32 weeks.
The equipment used in all the evaluations was the
VOLUSON1 730 (General Electric Medical Sys-
tems, Kretztechnik, Zipf, Austria), equipped with a
multi-frequency volumetric transducer with auto-
matic scan (RAB 3.5–5.0 MHz). All of the evalua-
tions were carried out by the same examiner (Araujo
Junior).
In each evaluation the following indices were
checked using the 2D method: biparietal diameter
(BPD), head circumference (HC), CTD, femur
length (FL), estimated fetal weight (EFW), amniotic
fluid volume, and placenta maturation and fetal
morphological evaluation. The EFW was calculated
according to the arithmetic average of the values
obtained from the fetal weight prediction charts
[13,14].
We were able to get the 3D view of the cerebellum
during fetal absolute rest and we also requested the
patient hold their breath for some seconds. The view
of the cerebellum was obtained with an automatic
scan transducer, which allows the capture of a
sequence of parallel planes with a scanning angle of
up to 908, with 4-second duration.
To get a view of the fetal cerebellum, we initially
scanned in real-time (2D method) searching for the
standard measures of the CTD, as described by
Goldstein et al. [1]. After obtaining the standard
view, we carried out the automatic 3D scan; thus we
were able to obtain the multiplanar and the surface
reconstruction modes.
We used the VOCAL method to obtain the
volume calculation. Initially, plane A was selected
(axial) as the reference plane; the tips of the organs
were delimited with the use of measure calipers and
the organ manually delimited in its external surface
with a 308 rotation angle (Figure 1). At the end of the
rotational process, the program automatically calcu-
lated the volume and it also supplied the 3D image of
the organ (Figure 2).
In order to evaluate the correlation of the
cerebellar volume with gestational age and with the
BPD, HC, CTD, FL, and EFW indices, we used
the Pearson’s correlation coefficient (r). Polynomial
regression models were created; gestational age was
used as the independent variable and the fetal cere-
bellar volume, as well as all of the indices of fetal
growth (BPD, HC, CTD, FL and EFW), were used
as the dependent variable. The definition of the order
of the polynomial was established starting from the
visual analysis of the dispersion diagram, and the
determination coefficient (r2) was used to evaluate
the adjustment of the estimated equation.
In all of the analyses a significance level of 5% was
used, and descriptive values that were inferior were
considered significant.
Results
All of the 52 selected patients fulfilled the inclusion
criteria, and they were included in the final analysis.
We carried out 141 measures of fetal cerebellar
volume; however, we were not able to measure two
fetuses at 32 gestational weeks, as we were unable to
obtain a clear visualization of the lateral limits of
the cerebellum. Therefore, for the final analysis, 139
measures were considered, corresponding to a
success rate of 98.6%.
The pregnant women were aged from 16 to 40
years (average 26.7 years, standard deviation 7.7
years). The number of gestations varied from one to
eight with an average of 2.1 gestations (standard devia-
tion 1.6 gestations). Postnatal results were obtained
from 40 patients (76.9%), and the weight of the
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Figure 2. Sonogram of the fetal skull using the VOCAL (virtual organ computer-aided analyses) method shows the three-dimensional
reconstruction of the cerebellum after its rotation in six consecutive planes, with its volume in cm3.
Figure 1. Sonogram of the fetal skull using the VOCAL (virtual organ computer-aided analyses) method shows the manual delimitation of
the cerebellum external surface on the axial plane (A) (top right).
Fetal cerebellar volume by 3D-sonography 583
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newborns varied from 2528 g to 4150 g, with an
average of 3185 g (standard deviation 410 g).
Our results indicate that the fetal cerebellar
volume is highly correlated with gestational age and
with all growth indices (BPD, HC, CTD, FL, and
EFW), with the best-fit polynomial regression
equation of a second-order to predict the fetal
cerebellar volume (r¼ 0.94; p5 0.001), and
p5 0.001 in all cases (Table I). As far as the fetal
growth indices are concerned, the best-fit equation to
predict the fetal cerebellar volume is also one of a
second-order (Figures 3–6), with the exception of
EFW, for which the best-fit equation is a linear one
(Figure 7).
Discussion
One of the greatest contributions of 3D US is linked
to volume calculation, especially for small structures
with irregular shape [15]. In the specific case of the
fetal cerebellum, which has a unique shape, the
calculation of its volume by multiplying its largest
axes by a constant (0.52) can lead to major mistakes
[5]. Since the cerebellar volume is the most objective
method for diagnosing cerebellar hypoplasia, 3D US
is a methodology more accurate and more appro-
priate than the 2D method when there is a suspicion
of malformations of the central nervous system
(CNS) with the presence of risks factors for the
posterior fossa [9].
In this study, we established the lower and upper
measurement limits of the fetal cerebellar volume at
the gestational ages of 20 weeks and 32 weeks,
respectively. The lower limit of 20 weeks was
determined due to the fact that up to 18 weeks some
structures of the posterior fossa such as the fourth
ventricle, the cisterna magna, the vermis, and the
cerebellar hemispheres, are still not completely
developed and, therefore, they can simulate abnor-
mal images [2]. The upper limit of 32 weeks was
chosen due to the difficulty in determining the
lateral parts of the cerebellum starting from the
35th week, for the following reasons: the insinuated
head, the relative lack of amniotic fluid around the
head, the closer contact with the uterine muscula-
ture, the shallow penetration of the ultrasound beam,
Table I. Pearson’s correlation coefficient (r) and polynomial
regression models for fetal cerebellar volume measured by three-
dimensional ultrasound, and various fetal biometrics.
Fetal
growth
indices r (p) b0 b1 b2 r2
GA 0.94 (50.001) 23.66 72.316 0.06 0.95
BPD 0.91 (50.001) 12.841 70.557 0.007 0.88
HC 0.90 (50.001) 18.855 70.203 0.0006 0.88
FL 0.91 (50.001) 11.404 70.649 0.01 0.92
CTD 0.87 (50.001) 4.578 70.466 0.015 0.95
EFW 0.96 (50.001) 71.91 0.006 0.92
GA, gestational age; BPD, biparietal diameter; HC, head
circumference; FL, femur length; CTD, cerebellar transverse
diameter; EFW, estimated fetal weight.
Figure 3. Dispersion graph of the fetal cerebellar volume from three-dimensional ultrasound with biparietal diameter (BPD).
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the darkening of the posterior fossa content, and the
fetal head in an occipital posterior position [16].
In this study we opted for the use of the VOCAL
method for volume calculation, because this meth-
odology, in spite of being a new one, has already
proven its reproducibility both in vivo [11] and
in vitro [10]. When compared to the multiplanar
method, this technique has the advantage of allowing
the modification of the outline of the organ, which is
of great interest as far as the fetal organs (which have
irregular shapes) are concerned [17].
In this study, we were unable to measure the
cerebellum volume in only two patients, both of
them at 32 gestational weeks. This high success rate
is partly due to the upper gestational age limit of the
study being set at 32 weeks, because of difficulties in
Figure 4. Dispersion graph of the fetal cerebellar volume from three-dimensional ultrasound with head circumference (HC).
Figure 5. Dispersion graph of the fetal cerebellar volume from three-dimensional ultrasound with cerebellar transverse diameter (CTD).
Fetal cerebellar volume by 3D-sonography 585
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obtaining clear images of the fetal cerebellum after
that gestational age.
We observed a high correlation of the fetal
cerebellar volume with gestational age, a result
similar to that obtained by Chang et al. [9] in the
Taiwanese population (r¼ 0.91; p5 0.0001). With
regard to the polynomial regression models using the
volume of the fetal cerebellum as the dependent
Figure 6. Dispersion graph of the fetal cerebellar volume from three-dimensional ultrasound with femur length (FL).
Figure 7. Dispersion graph of the fetal cerebellar volume from three-dimensional ultrasound with estimated fetal weight (EFW).
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variable and the indices of the fetal growth as
independent variables, the best-fit equation to pre-
dict the fetal cerebellar volume was the second-order
one, with the exception of EFW in which the best-fit
equation was a linear one. Our results were similar to
those obtained by Chang et al. [9]. As we analyze
these results, it becomes clear that the fetal cerebellar
volume is an important index to evaluate fetal
growth. However, it is important to stress that the
regression coefficient models obtained in this study
were different from those obtained by Chang et al.
[9], which demonstrates the need for us to obtain our
own equations.
We should stress the strong correlation between
the CTD and the fetal cerebellar volume (r¼ 0.87;
p5 0.001). This correlation was not evaluated in
Chang’s study [9]. Since it is known that the CTD
varies in different ethnic groups at the same gesta-
tional age [12], and since the cerebellar volume is
highly correlated with this index, we could also infer
that the cerebellum volume should vary in different
populations. Therefore, the reference volume inter-
vals of fetal cerebellum determined in homogeneous
populations such as the one in Taiwan cannot be
applied to heterogeneous populations such as that of
Brazil. Also, as the CTD is an important index for
establishing gestational age in fetuses with a suspicion
of intrauterine growth restriction [18,19], the volume
of the fetal cerebellum could be an appropriate index
for the evaluation of fetuses with a suspicion of this
pathology.
In short, we believe that this study has contributed
to the establishment of a new index for the evaluation
of fetal growth. However, it is important to stress
that other studies are necessary, especially multi-
center ones, to determine the real applicability of this
parameter.
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