PRENATAL DIAGNOSIS

Prenat Diagn 2009; 29: 326–339.

Published online 10 November 2008 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/pd.2146

REVIEW

Normal sonographic development of the central nervous

system from the second trimester onwards using 2D, 3D
and transvaginal sonography
Ana Monteagudo* and Ilan E. Timor-Tritsch
Division of Obstetrical and Gynecological Ultrasound, Department of Obstetrics and Gynecology, Professor of Obstetrics and
Gynecology, NYU School of Medicine, 530 First Avenue NB9N26, New York, NY 10016, USA

The developmental changes of the fetal central nervous system (CNS) during the second and third trimesters,
specifically the brain, relate mostly to changes in size. However, other changes do occur in the fetal brain
during the second and third trimester such as: the union of the cerebellar hemispheres, development of the
corpus callosum (CC), and increasing complexity of the cerebral cortex. These changes follow a well-defined
developmental timeline recognizable by sonography.
The fetal neuroscan can be divided into a ‘basic scan’ which is performed transabdominally and a
‘targeted Exam or neurosonogram’ which uses a multiplanar approach, which preferably should be performed
transvaginally. During the ‘basic scan’, several brain structures are imaged in addition to obtaining important
biometric measurements. The ‘neurosonogram’ is a more extensive or detailed fetal study during which the
emphasis is on the addition of coronal and sagittal planes. The easiest way to obtain these planes, if the fetus is
in a cephalic presentation, is the transvaginal route. Three-dimensional (3D) sonography should, if possible, be
performed transvaginally using the multiplanar approach. An added benefit of 3D sonography is the ability to
display and render the volume in a variety of ways which may enhance the detection of pathology. Copyright
 2008 John Wiley & Sons, Ltd.
KEY WORDS: neurosonography; transvaginal sonography

INTRODUCTION drawback of the transvaginal technique was that the axial

Sonography is the best and most used tool to docu-
ment, study and understand the anatomy, pathology and
developmental changes of the fetal central nervous sys-
tem (CNS). Over the past 30 years, as the technology
has evolved so has our understanding and our ability
to image the fetal brain. When the first ultrasound (US)
machines were introduced, the bony skull was the first to
be imaged; this enabled the development of nomograms
of fetal growth. Since at that time only transabdomi-
nal probes were used, the fetal brain was studied using
only or mostly the axial planes. One major draw back
was that as the gestational age increased, the density
(ossification) of the cranial bones increased; therefore,
the hemisphere close to the transducer appeared blurred
permitting to study mainly the hemisphere distal to the
probe which was clearly imaged. The introduction of the
transvaginal probes allowed us to place the transducer in
close proximity to the head and obtain coronal and sagit-
tal views through the acoustic window provided by the
fontanels and sutures. This way both hemispheres could
be seen simultaneously (Monteagudo et al., 1991). The
*Correspondence to: Ana Monteagudo, Division of Obstetrical
and Gynecological Ultrasound, Department of Obstetrics and
Gynecology, Professor of Obstetrics and Gynecology, NYU
School of Medicine, 530 First Avenue NB9N26, New York, NY
10016, USA. E-mail: Ana.Monteagudo@med.nyu.edu
plane could rarely be imaged and that serial sections had
to be obtained one at a time. At present, volume scanning
(3D sonography) allows us to scan transabdominally or
transvaginally, obtaining images in all three classic scan-
ning planes and thus giving us the ability to view the
brain through serial sections in all three classic planes
as well as in any other desired planes of our choice
(Monteagudo et al., 2000). In addition, several post-
processing features assist us in highlighting pathology
that may not be otherwise obvious. Therefore, in current
obstetrical scanning, especially as it relates to the fetal
CNS, multiple technical approaches are simultaneously
used (i.e. 2D and 3D transabdominal and transvaginal
sonography).
THE FIRST TRIMESTER
A detailed description of the CNS in the first trimester is
not the central topic of this review; however, before we
proceed several important issues about the development
of the CNS necessary to set the stage for this review
should be mentioned.
The first trimester ends at the 14th week of the
pregnancy. It is during this period of its development,
that the CNS undergoes tremendous transformation. The
embryo starts as a flat disc that undergoes cranial,

Copyright  2008 John Wiley & Sons, Ltd. Received: 1 July 2008
Revised: 25 September 2008
Accepted: 25 September 2008
Published online: 10 November 2008
 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER
lateral and caudal folding. This process is completed
by approximately the 6th postmenstrual week.
Using sonography, we can begin to examine the devel-
oping embryonic brain from the 7th postmenstrual week,
when the head becomes discernible from the rest of the
body and the primitive embryonic ventricular system can
be imaged. The 8th postmenstrual week reveals the four
convoluted sequential sonolucencies in the embryonic
head that correspond to the telencephalon, diencephalon,
mesencephalon and metencephalon. From approximately
the 9th postmenstrual week, the fetal period begins and
the falx cerebri and the choroid plexuses (CPs) in the
lateral ventricles can be imaged; these are important
landmark in the development of the CNS.
SECOND AND THIRD TRIMESTER
DEVELOPMENTAL CHANGES OF THE FETAL
BRAIN
The second trimester begins during the 14th week of
the pregnancy and extends through the 27th week of the
gestation. During the second and the third trimesters, the
CNS slows its developmental pace. However, this period
is characterized by an unparalleled growth of the brain
volume; there is nearly a 40-fold increase in the weight
of the brain between the end of the embryonic period and
birth (O’Rahilly and Muller, 2008). In addition, some of
the brain structures, which began their developmental
journey during the first trimester, continue to evolve or
change through the second and third trimester. Some
structures may not reach their full ‘mature state’ until
several months after the birth of the infant. Changes that
occur in the fetal brain are: the union of the cerebellar
hemispheres, development of the corpus callosum (CC),
the cerebral cortex, which becomes thickly populated
by neuronal migration and more complex, the insula
which becomes buried by the opercula. There is a
backward projection of the occipital lobes and formation
of the posterior horns (PHs) of the lateral ventricles,
development of gyri and sulci, and asymmetry of the
right and left hemispheres (O’Rahilly and Muller, 2008).
Some of these changes can be imaged by US especially
those that relate to the CC, cavum septi pellucidi (CSP),
ventricular system, cerebellum, vermis, and finally the
development of gyri and sulci.
Before we go over the developmental changes that
occur in the fetal brain during the second and third
trimesters of pregnancy, it is imperative to review the
anatomy of the brain using the multiplanar approach.
The multiplanar approach (which in fact means scrolling
or navigating within the acquired volume of the brain in
the orthogonal planes) should always be used when brain
pathology is present or suspected.
SONOGRAPHIC NEURO-ANATOMY IN THE
AXIAL, CORONAL AND SAGITTAL PLANES
The axial plane is the most frequently used plane in
obstetrics, since this is the plane in which the biometric
measurements of the head [e.g. biparietal diameter
Copyright  2008 John Wiley & Sons, Ltd.
327
(BPD)] are performed. The three most clinically useful
levels or sections at which the axial images are produced
are: transventricular, transthalamic and transcerebellar
(ISUOG Guidelines, 2007) (Figure 1).
• The landmarks for the transventricular axial plane
from anterior-to-posterior are as follows: the CSP,
flanked in each side by the anterior horns (AHs)
of the lateral ventricles; caudally the PHs of the
lateral ventricle, which contain the hyperechoic CPs.
The walls of the ventricles are echogenic and are
clearly demarcated by the fluid contained within the
ventricles. At this level, the lateral ventricles are
measured at its widest part; at the level of the glomus.
In this section, the CP is seen filling bilaterally
the cavity of the ventricles. The calipers are placed
perpendicular to the axis of the ventricles touching
the inner aspect. A measurement of up to 10 mm is
deemed normal (Almog et al., 2003) (Figure 1A).
• Inferior to the transventricular plane, the transtha-
lamic plane can be obtained. The landmarks from
anterior-to-posterior are: the frontal horns of the lat-
eral ventricles, CSP, thalami and the hippocampal
gyri (HG). It is at this level that most of the bio-
metric measurements of the head are obtained: BPD,
head circumference (HC) and occipitofrontal diameter
(OFD) (Figure 1B).
• The transcerebellar axial plane is inferior to the
transthalamic plane and is slightly tilted posteriorly to
adequately image the posterior fossa. The landmarks
from anterior-to-posterior are: frontal horns of the
lateral ventricles, CSP, thalami, cerebellum, and the
cerebello-peduncular cistern [cisterna magna (CM)].
A CM measuring greater than 10 mm is considered
abnormal; also considered abnormal is the lack of
its visualization strongly suggesting a spinal defect
(Figure 1C).
In contrast to the axial plane easily obtainable by
transabdominal sonography, the coronal and sagittal
planes are easier to obtain by transvaginal sonography;
that is, if the fetus is in cephalic presentation. However,
transabdominally the frontal suture can be used as an
acoustic window to obtain the transfrontal view of the
brain. This view can be use to image the median brain
structures such as CC, CSP, and cerebellum (Visentin
et al., 2001). This view can be routinely obtained during
the screening anatomical scan; however, when a targeted
neuroscan is performed the transvaginal route provides
better resolution especially if the fetus is in a cephalic
presentation.
When scanning transvaginally, the sections are
obtained through the anterior fontanelle or one of the
sutures of the skull; therefore, both hemispheres can
be effectively imaged therefore compared to each other
for symmetry. Although, a large number of coronal as
well as sagittal sections are technically possible, con-
centrating only on four coronal and two sagittal sections
will yield valuable and diagnostically necessary addi-
tional information to those obtained by the axial sections
(Timor-Tritsch and Monteagudo, 1996; Monteagudo and
Timor-Tritsch, 1997; ISUOG Guidelines, 2007). In the
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328 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH

Figure 1—The three standard views of the fetal brain using the axial plane are demonstrated. (A) Transventricular plane is the plane in which
the lateral ventricle is routinely measured. The anatomic structures seen are: cavum septi pellucidi (CSP), the anterior horn (AH), the posterior
horn (PH) and the choroid plexus (CP). (B) Transthalamic plane is the plane in which most of the biometric measurements of the fetal head [i.e
biparietal diameter (BPD) and head circumference (HC)] are performed. In this plane, in addition to the anterior horn, cavum septi pellucidi, the
thalami (TH) and the hippocampal gyri (HG) are seen. (C) Transcerebellar plane is a plane that is tilted posterior. The anterior landmarks of the
brain are similar to those seen in the transthalamic plane; but posteriorly the cerebellum (C) and the cisterna magna (CM) are seen

majority of cases, the combination of these sections is
sufficient to arrive at the diagnosis.
CORONAL SECTIONS
The four sections to be described here from anterior-
to-posterior are: the frontal-2 or transfrontal plane,
mid-coronal-1 or transcaudate plane, mid-coronal-2 or
transthalamic plane and the occipital-1 and -2 or tran-
scerebellar plane (ISUOG Guidelines, 2007) (Timor-
Tritsch and Monteagudo, 1996) (Figure 2).
• The landmarks for the frontal-2 or transfrontal plane
are as follows: interhemispheric fissure (IHF), which
equally divides the right and left hemispheres; the
AHs of the lateral ventricles. The bony structures
seen are the sphenoidal bone as well as the orbits
(Figure 2A).
• In the mid-coronal-1 or transcaudate plane moving
from superior-to-inferior, the structures seen are: the
IHF, the hypo-echoic horizontal lines of the CC, the
anechoic triangular CSP, flanked on both sides by the
anechoic frontal horns of the lateral ventricles. The
most inferior structure evident is the caudate nuclei.
Bilaterally, close to the bones of the cranium, the
indentations of the insula are apparent (Figure 2B).
• Moving more posterior, the next plane is the mid-
coronal-2 or transthalamic plane. This is an important
view, since a significant number of pathologies can
be identified by carefully studying this plane. The
structures from superior-to-inferior are similar to
those viewed in the previous section but instead of
the caudate nucleus (CN) the thalami are seen. The
3rd ventricle is situated in the midline between the
thalami; if prominent it is usually a part of a generally
dilated ventricular system (Figure 2C).
• The occipital-1 and -2 or transcerebellar plane is
the most posterior plane. The structures seen from
superior-to-inferior are: the IHF, the occipital horns of
the lateral ventricles, which on this plane are devoid
of CPs seen on the previous planes and appear round,
rendering this plane the owl’s face configuration. Infe-
rior, below the tentorium, the contents of the posterior

Copyright  2008 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 326–339.
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 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER 329

Figure 2—Using transvaginal sonography the fetal brain is scanned using four serial coronal planes. (A) Frontal-2 or transfontal plane; this is a
very anterior plane that cuts through the orbits. The brain structures seen are the anterior lobe of the brain separated into two equal parts by the
interhemispheric fissure (IHF). (B) Mid-coronal-1 or transcaudate plane is slightly posterior to the frontal-2 plane. The anatomic landmarks seen
from top to bottom are: the interhemispheric fissure (IHF), the corpus callosum (CC), the cavum septi pellucidi (CSP), anterior horns (AH) and
caudate nucleus (CN) to each side of the CSP and the insula (INS) just below the fetal cranium. (C) Mid-coronal-2 or transthalamic plane. Many
of the anatomic landmarks seen on the mid-coronal-1 are seen in this plane as well. However, the thalami (TH) replace the candate nucleus.
Occasionally, the third ventricle can be seen as a slit-like anechoic structure between the thalami. (D) Occipital-1 and 2 or transcerebellar plane.
In this posterior plane, the posterior horns (PH) of the lateral ventricles appear as rounded structures devoid of the choroid plexus. Below the
posterior horn, the posterior fossa is seen containing the cerebellum (C) and the cisterna magna (CM)

fossa are seen: the cerebellum, the vermis and the
cerebello-peduncular cistern (CM) (Figure 2D).
SAGITTAL SECTIONS
hemorrhage), the quadrigeminal plate and cistern
(frequent place of arachnoid cysts). Sectoring more
posteriorly, the vermis of the cerebellum, the 4th
ventricle and the CM can be seen (Figure 3B).

The two clinically significant sagittal sections are the
median plane and the two left-and-right oblique-1 or
parasagittal planes (Figure 3).
• The right-and left-oblique-1 or parasagittal planes
reveal the anterior, posterior and at times the infe-
rior horns of the lateral ventricle and are seen
as an inverted ‘C’ containing the echogenic CPs
(Figure 3A).
• The median plane is one of the most important
and diagnostically useful planes depicting all of the
midline structures, namely the CC, pericallosal artery
(PCA) (using power Doppler evaluation), located
superior to and hugging the CC, the area of the
3rd ventricle. The tela choroidea (TC) covering the
thalamus (locus of the germinal matrix prone to
VOLUME OR MULTIPLANAR SONOGRAPHY: 3D
ULTRASOUND
Volume sonography is better known as 3D sonography;
it shortens the process of obtaining the serial sagittal
and coronal sections (Monteagudo et al., 2000; Timor-
Tritsch et al., 2000a). There are differences between the
planes obtained by two-dimensional (2D) transvaginal
or transabdominal sonography from 3D transvaginal
sonography. Using 2D US, all sections arise from a
single point (the transducer tip) usually at the anterior
fontanelle, and fan-out in a radial fashion; the planes
are oblique to one another. However, when using 3D
transvaginal sonography the sections derived from the
volume are parallel to each other similar to those
obtained by computed tomography (CT) or magnetic

Copyright  2008 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 326–339.
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330 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH

Figure 3—The sagittal plane is seen mostly when transvaginal sonography is used. (A) Oblique-1 or parasagittal plane is a very useful plane
since the three components of the lateral ventricles can be seen: the anterior horn (AH), the posterior horn (PH) and the inferior horn (IH). In
addition, the thalami and the choroid plexus are also evident in this section. (B) Median or mid-sagittal plane is an essential plane since the
corpus callosum (CC) can be seen in its entirety. Below the corpus callosum the anechoic cavum septi pellucidi (CSP) is seen, as well as the
area where the third ventricle (3V) is located between the two portions of the thalami; the tela choroidea (TC) is the choroid plexus of the third
ventricle. Posteriorly the posterior fossa is seen, the most echogenic structure present is the vermis (V) of the cerebellum, the fourth ventricle
(4V) is an anechoic, triangular in shape and is located anterior to the vermis and the cisterna magna (CM) is the anechoic area between the back
of the vermis and the cranium. Using color Doppler the pericallosal artery (PCA) is seen

resonance imaging (MRI) (Figure 4). The images of the

sections that are below the fontanelle and sutures have
higher resolution than those that are more lateral or distal
from the acquisition plane. Another difference between
the 2D and 3D transvaginal sonography is that with 3D
sonography a reconstructed axial plane (the C -plane)
is possible; therefore, all three scanning planes can
be simultaneously displayed on the screen (orthogonal
planes) (Figure 5). The user can scroll to navigate in a
continuous fashion through each plane at will.

HOW IS TRANSVAGINAL OR
TRANSABDOMINAL 3D NEUROSONOGRAPHY
DONE?
Acquisition, storage and display are the three basic steps
in performing a 3D US study. This section will review
these basic steps.
Step 1: Data acquisition:
This first step (the data acquisition) is the most important
step in the process of creating clinically diagnostic
images. Remember that poor quality 2D images will
create poor quality 3D images! Therefore it is not
only worth, but also mandatory to optimize the
Figure 4—Three dimensional rendered faces are used to demonstrate
the difference between the direction of the transvaginally generated
2D planes and those studied from a 3D volume of the brain.(A) When
scanning using 2D US through the anterior fontanelled, the planes
arise from a single point (fontanenlle) and fan-out laterally. The
sectional planes are comparable to those obtained by neonatal trans-
fontanelle imaging. (B) Successive planes obtained using 3D volume
scanning are parallel to each other similar to those obtained when
using a CT or an MRI
grayscale 2D image. Once the brain is clearly seen on
the screen, several volumes should be captured; if the

Copyright  2008 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 326–339.
DOI: 10.1002/pd
 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER
Figure 5—After a brain volume has been acquired, the three orthog-
onal planes are displayed; in ‘box A’—the coronal section, in ‘box
B’—the sagittal with the fetus facing the left side of the screen and
in ‘box C’—the axial
volume is being captured transvaginally one should
be in the sagittal plane and one in the coronal plane.
The volume acquired in the sagittal plane enables
a diagnostic view of the structures in the median
plane. The one acquired in the coronal plane permits
scrolling in the coronal plane. The ‘reconstructed’
plane; in this case the axial, may be of somewhat
lower resolution; however, it still is instrumental in
making clinically relevant observations. When the
volumes are captured transabdominally, we obtain
one in the axial plane at the level of the BPD and the
second either in the coronal or sagittal depending on
the fetal position. We display the orthogonal planes on
the screen as follows: in box A, the coronal section of
the head; in box B, the median sagittal with the fetal
face facing the box A and box C, the axial section
with the posterior fossa being superior on the screen
(Figure 5).
Step 2: Data Storage.
The volume data is stored in the computer as a volume
of data points in a Cartesian system and can be reused
to display images using different technologies.
Step 3: Display
There are multiple displays that may enhance certain
features of the volume and assist in making the
clinical diagnosis. We have arranged the displays in
the order that we usually use them.
Multiplanar imaging (orthogonal planes) is the first
type of display that we use. The three scanning planes
(sagittal, coronal and axial) can simultaneously be dis-
played at right angles to each other on the US monitor. In
this display, it is possible to scroll or navigate in a con-
tinuous fashion through each plane at will. If the volume
was obtained either in a coronal or sagittal plane, the
axial plane generated is a reconstructed plane (Figure 5).
The tomographic display is useful since it allows
visualization of multiple parallel slices at different
spacing through a volume at the same time on the
US screen; therefore, serial sections of any of the
Copyright  2008 John Wiley & Sons, Ltd.
331
Figure 6—Tomographic display showing serial coronal sections from
anterior (A) to posterior (P). The central picture is highlighted by the
box around it and the thicker white line. The marker dot is seen in
the midline on the corpus callosum. The slices between the interval
is 3 mm. Arrows point to the occiput
Figure 7—This figure shows a tomographic display of Sagittal
sections. Similar to Figure 7, the central picture is highlighted by
the box around it and the thicker white line. The marker dot is in
the midline on the corpus callosum and the slice interval is 3 mm.
However, the arrows point to the right and left side of the face;
therefore both right (R) and left (L) of the median sections are seen
planes similar to those seen by CT or MRI are possible
(Figures 6 and 7).
The thick slice display in which the selected area of
the volume is collapsed into a 2D image can enhance
edges, improve contrast detection and at times give
more depth to the image (Figure 8). Volume contrast
imaging (VCI ) is another software application enabling
the display of a number of slices ‘collapsed’ into one
2D picture enhancing tissue borders. The thick slice and
the VCI are essentially the same. Thick slice rendering
requires several steps: placing a rendering box on the
orthogonal planes, narrowing it to a minimum and
displaying the rendered image, which represents the 2D
(thick slice) ‘image of many collapsed 2D images’. This
process basically is an edge enhancement process. VCI
is essentially the same process, which is achieved by
touching one of the control knobs. It represents the 2D
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332 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH
Figure 8—The thick slice display is demonstrated. The box shows
the selected area of the volume in all three planes which has been
‘collapsed’ into a 2D image with enhanced edges, contrast and
apparently more depth to the image (lower right image)
(collapsed) image of a certain number of 2D slices. It
is possible to control the slice thickness from 2–5-mm
thick slices.
3D sonoangiography which enables selective imaging
of blood vessels after a 3D acquisition of a power
or color Doppler containing volume is very useful,
especially in agenesis of CC where absence of the PCA
aids in the diagnosis (Figure 9).
The inversion mode is one in which the selected fluid
filled areas of the acquired volume can be ‘inverted’
and therefore, the areas, which were initially anechoic
become echogenic. The on-screen appearance is that of a
cast representing the fluid filled space—in this case the
lateral ventricles. This is useful in cases of hydrocephaly
in which the ventricles are enlarged with cerebral spinal
fluid (CSF) (Figure 10).
Surface rendering is the most widely known display.
The surface features can be seen and recognized resem-
bling a photograph (e.g. the face) (Figures 1–4). This
is useful since certain brain anomalies are associated
Figure 9—The 3D sonoangiography display allows selective imaging
of blood vessels after a 3D acquisition of a power or color Doppler
containing volume has been acquired. Arrows represent the perical-
losal artery
Copyright  2008 John Wiley & Sons, Ltd.
Figure 10—In the inversion rendering a selected, fluid filled areas of
the acquired volume (in this case: ventricles) can be seen, which were
initially anechoic thus become echogenic. (A) A parasagittal view of
the on-screen appearance of the ‘cast’ like fluid filled space of the
lateral ventricle. (B) The ‘inverted’ image now demonstrates the two
ventricles parallel to each other. Between the two, the interventricular
foramina connecting to the third ventricle can be appreciated
with facial dysmorphism, such as is the case with alobar
holoprosencephaly.
The X-ray, maximum (‘bone’) or transparency mode
allows selective imaging of the fetal cranium (or bones),
as well as defining the sutures. In neurosonography, this
is probably the display that is least used. In contrast,
when searching for anomalies of the bony skeleton this
is an invaluable tool.
At this point, we will review the developmental
changes of fetal brain that occur during the second and
third trimesters of pregnancy. It is relevant to point
out that many of the developmental changes of the
brain follow a very specific and defined developmental
timeline. Therefore, establishing the correct gestational
age of the fetus is the key to the correct interpretation
of the anatomy seen.
THE CORPUS CALLOSUM
The CC, the CSP and the cingulate gyrus are devel-
opmentally very closely related. On the median section
the CC is located between the cingulate gyrus, which
is above it and the CSP, which is below it. The CC
arises from the commissural plate and is a pathway of
fibers that connect the cerebral hemispheres with each
other. Initially, the CC is a compact mass of tissue, but
as the pregnancy progresses it significantly lengthens in
size. The CC develops in a front-to-back (or rostral-
to-occipital) fashion creating a cover over the roof of
the third ventricle; the underlying portion of the com-
missural plate becomes thinned and forms the septum
pellucidum (O’Rahilly and Muller, 1992, 2001). The
development of CSP is closely associated with that of
the CC; there cannot be a CSP without a covering CC;
however, a CC can be present in the absence of the CSP
such as in septo-optic dysplasia (Figures 11 and 12).
Transvaginal 2D and 3D sonography allows imaging
of the CC relatively quickly and easily; however,
this can also be done by transabdominal sonography.
Sonographically, the CC is anechoic. When color or
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 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER 333

A B C

Figure 11—This figure targets the corpus callosum in the median plane. (A) At 34 weeks, the corpus callosum is seen just below the cingulate
gyrus. (B) The ‘anatomy’ of the corpus callosum is depicted at 22 weeks. CSP represents Cavum septi pellucid; CV represents Cavum vergae
(C) At 16 weeks of gestation, the median section is normal for age. However, the corpus callosum, cavum septi pellucidi and cingulate gyrus
are still absent due to their later appearance

Figure 12—The normal and pathological findings of the median section. (A) In the median plane, a normal appearing corpus callosum (CC) and
cavum septi pellucidi (CSP). (B) In a coronal section, the cavum septi pellucidi (CSP) is seen below the corpus callosum. Note the thin walls of
the CSP separating it bilaterally from the anterior horns (AH) of the lateral ventricles. (C) In this median section, the corpus callosum and the
CSP are seen appearing normal. (D) The same fetus as in C; when scanned coronally the thin walls of the CSP that normally separate it from
the anterior horns are not evident. This can be seen in cases of lobar holoprosencephaly as well as in septo-optic dysplasia. (E) In the median
plane, the corpus callosum cannot be seen; instead a relatively large anechoic structure is seen. 3V represents third ventricle. (F) In the coronal
plane, the upwardly displaced third ventricle is touching the lower most part of the falx

power Doppler US is added, the pericallosal arteries
(there are two of them: one on each hemisphere) can be
seen superior to the CC following their inner margin.
The CC has several parts: the rostrum (beak), genu
(knee), corpus (trunk) and the splenium (tail) (Figures 11
and 3B). It can be seen in its full developmental shape
from 18–20 weeks of the gestation. The CC continues
to grow reaching its final adult-like appearance at around
the 28th postmenstrual week.
THE CAVUM SEPTI PELLUCIDI
The CSP is a fluid filled space; its boundaries are
superiorly the CC and laterally the two thin and
translucent membranes of the septum pellucidum and
the fornices. At times, a posterior portion is seen and is
called the cavum vergae (Figure 11B). We can begin to
image the CSP as early as the 15th postmenstrual week;
however, it cannot be consistently imaged until the
16th–17th week of the pregnancy. As term approaches,
the CSP begins to narrow in an occipital-to-rostral fash-
ion. In normal pregnancies, a CSP should be seen in
all fetuses between 18th and 37th postmenstrual weeks.
After the 38th postmenstrual week, it is only imaged in
approximately 70% of the fetuses. It has been reported
that as many as 50% of term neonates will have a CSP
present, but by the 3–6 months of life only 15% of
infants will have a CSP. In adults, the CSP is totally

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334 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH

Figure 13—In the axial section: (A) The sonographic appearance of the fornix is that of two hypo-echoic parallel with a central echogenic
line. (B) The cavum septi pellucidi resembles a box-like structure located between the anterior horns of the lateral ventricles with a central
anechoic core

obliterated and appears as an echogenic line. The sono-
graphic appearance of the CSP is that of a rectangular
box-like structure located between the AHs of the lat-
eral ventricles. This should not be confused with the two
hypo-echoic parallel columns of the fornix, which have
a central echogenic line and these are seen in a slightly
inferior section to the one in which the CSP is seen
(Figure 13). The size of the CSP increases gradually
from the 18th postmenstrual week to 27th week and then
plateaus. The mean width of the CSP is 5.3 ± 1.7 mm;
therefore a CSP greater than 10 mm is deemed to be
dilated. Lack of visualization of the CSP between 18
and 37 weeks of gestation should raise the suspicion
that it is absent. Absence of CSP is a feature age-
nesis of the CC, holoprosencephaly, septo-optic dys-
plasia, schizencephaly, porencephaly/hydranencephaly,
basilar encephaloceles and severe hydrocephaly. At this
time, it is virtually impossible to use US to differenti-
ate between septo-optic dysplasia and lobar holoprosen-
cephaly. Some of the isolated lobar holoprosencephalies
may carry a good prognosis. At this time there is contro-
versy in the literature about the significance of a dilated
CSP; however, it has been associated with chromosomal
aneuploidy as well as congenital anomalies (Jou et al.,
1998; Falco et al., 2000; Sherer et al., 2004; Pilu et al.,
2005; ISUOG Guidelines, 2007; Callen et al., 2008).
THE VENTRICULAR SYSTEM
The ventricular system consists of the lateral ventricles,
the third and fourth ventricle, and the interventricular
foramina (Monro) which connects the lateral ventricles
to the third ventricle, the cerebral aqueduct (Sylvius)
which connects the third ventricle with the fourth ven-
tricle, median aperture (Magendi) which connects the
fourth ventricle with subarachonoid space and cere-
bellomedullary cistern (CM) and the lateral apertures
(Luschka), which connect the fourth ventricle with the
subarachnoid space as well as the cistern of the great
cerebral vein.
The lateral ventricles are positioned in a parallel man-
ner within the cerebral hemispheres and have three horns
anterior, posterior and inferior, a body and a triangu-
lar atrium (Figures 3A and 14). The lateral ventricles
undergo significant changes in size and shape during the
second and third trimesters of the pregnancy. Initially,
late-first-trimester-to early-second trimester, the lateral
ventricles appear large due to the thin brain parenchyma
and consist mostly of an AH and inferior horn, but as the
pregnancy progresses it gradually become more slender.
The PHs of the lateral ventricle develop late in compar-
ison to the AH and inferior horns. The occipital lobes of
the brain grow by projecting backward which enables
the formation of the PHs of the lateral ventricles. At
12 weeks of gestation, the lateral ventricles are essen-
tially ‘C-shaped’ and no PHs are present; however, as

A B C

Figure 14—Using 2D transvaginal US the ‘three-horn view’ of lateral ventricles are seen in the oblique-1 or parasagittal section. (A) At 12 weeks,
the lateral ventricles appear relatively large due to the thin brain parenchyma and consist mostly of an anterior and inferior horn. The choroid
plexus appear relatively large and almost fills the entire ventricle. (B) By 15 weeks, the choroid plexus has ‘moved’ posteriorly leaving a relatively
large anterior horn. (C) By the 20th week of gestation, due to growth of the fetal brain the lateral ventricles are slit-like

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DOI: 10.1002/pd
 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER
pregnancy progresses the PHs grow and at the 18th week
of gestation a clearly defined PH is seen (Figure 14).
The width of the lateral ventricles, as measured in the
axial transventricular plane, remains constant through-
out the pregnancy with a normal measurement at less
than 10 mm. Using 2D transvaginal sonography, the
lateral ventricles can be imaged in the coronal and
sagittal planes. In the coronal section, the normal sono-
graphic appearance of the AHs of the lateral ventricles
before the 18th week is that of a ‘plump’ comma-like
fluid filled structure flanking the CSP; after 18th week,
the width decreases eventually becoming ‘slit-like’. The
three horns of the lateral ventricles can be visualized
with 2D transvaginal sonography when an oblique sec-
tion of the brain is obtained; this section is lateral to
the median section of the brain. When using 3D, a
‘3-horn view’, is possible after the volume has been
tilted so that a plane is generated to reveal all three
horns (Timor-Tritsch et al., 2000b) (Figure 15).
Dilation of the lateral ventricles can be a clue to
several pathologies such as spina bifida and agenesis of
the CC. The size of the lateral ventricles is influenced by
fetal gender and in the absence of any other structural
and karyotypical abnormalities, normal male fetuses are
more likely to have lateral ventricles measuring slightly
more than 10 mm when compared to normal female
fetuses of the same gestational age (Signorelli et al.,
2004; Gaglioti et al., 2005).
The third ventricle can be imaged in the majority of
fetuses during pregnancy. Early in the second trimester,
the appearance of the third ventricle by transabdominal
Figure 15—To display ‘three-horn views,’ when a brain volume has been obtained, the coronal plane has to be tilted to the right and subsequently
to the left to see the entire ventricle. Using the tomographic display, the coronal section was tilted to the right and multiple parasagittal sections
of the brain were displayed
Copyright  2008 John Wiley & Sons, Ltd.
335
sonography is that of a single echogenic line between
the thalami. However, during the third trimester the
cerebro-spinal fluid fills the cavity of the third ventricle
and the transabdominal appearance changes to two
parallel lines separated by an anechoic area between the
thalami. During the second trimester, the size of the third
ventricle ranges from 1–2 mm. Its mean ventricular
width after 32 weeks is 2.7 ± 0.4 mm; 3.6 mm (two
standard deviation above the mean) is the upper level
of normal (Sari et al., 2005).
The fourth ventricle is located posterior to the pons
and upper part of the medulla and anterior to the cere-
bellum. It has a characteristic diamond shape in cross-
sections of the human brain. Cerebro-spinal fluid enter-
ing the fourth ventricle through the cerebral aqueduct
can exit to the subarachnoid space of the spinal cord
through two lateral aperture (Luschka) and a single,
median aperture (Magendie). When scanning transvagi-
nally in the median section, the fourth ventricle can be
clearly seen by its anechoic fluid filled contents. Only
the median aperture is seen sonographically (on axial
planes) and only at ages less than 15–16 postmenstrual
weeks.
The CPs are an integral part of the ventricular system.
They are made of multiple villi with rich blood supply,
which provide a large surface area to produce the
cerebro-spinal fluid filling the ventricular system. During
the first trimester the CP fills the entire lateral ventricle;
but as the pregnancy progress, their size compared to
that of the lateral ventricle decreases. Early in pregnancy
they are located in the AH of the lateral ventricles;
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336 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH

Figure 16—The posterior fossa. A and B are axial sections and C and D are median (Sagittal) sections (A) The upper surface of the cerebellum
(C) and the midline vermis (V). (B) Posterior to the cerebellum the cisterna magna (CM) is seen containing the cisterna magna septa. (C) Median
section demonstrates anteriorly the corpus callosum and in the posterior fossa, the echogenic vermis is clearly seen. The fourth ventricle (4V)
appears as a triangular indentation in the anterior aspect of the vermis. (D) A magnified view of the vermis, fourth ventricle (4V), cisterna magna
and the tentorium of the cerbellum (T)

but as the CP ‘moves’ posteriorly and assume their
final position within the atrium of the lateral ventricle,
the lateral ventricle appears relatively large. Therefore,
when scanning the fetal brain at 14–15 weeks the lateral
ventricles appear prominent; this is most obvious in the
axial as well as the parasagittal sections. Abnormalities
of the CP, such as thin or dangling choroids, are
associated with ventriculomegaly and/or hydrocephaly.
A separation of the CP from the median wall of the
lateral ventricle of up to 3 mm is considered to be
normal. However, if measured beyond 3 mm, a careful
evaluation of the fetal brain is necessary. When isolated,
CP separation of more than 3 mm is seen during the
second trimester; it is usually a transient finding and in
majority of the cases resolution occurs within 1 month;
most infants will have no abnormalities (Bronsteen
et al., 2006).
and 17). It recently has been suggested that deviation
from its normal appearance (i.e. the lack of them) may
be an early marker of abnormalities of the cerebellum,
vermis and brain stem, therefore in these cases a targeted
scan of the posterior fossa using multiplanar imaging is
suggested (Robinson and Goldstein, 2007). In pregnan-
cies of less than 20 weeks, obtaining low axial section,
that is too inferior, may falsely give the impression of a
vermian defect (Figure 18). This is due to the fact that
the development of the cerebellar vermis occurs from
a superior (rostral) to an inferior (caudal) fashion and
a normal connection between the fourth ventricle and
cerebellomedullary cistern can be demonstrated until the
development of the vermis is complete (Bromley et al.,
1994; Babcook et al., 1996; Malinger et al., 2001; Ben-
Amin et al., 2002) (Figure 18).

THE CEREBELLUM AND THE VERMIS
The posterior fossa includes the cerebellum, cerebellar
vermis and cerebellomedullary cistern (CM). In the tran-
scerebellar plane, in addition to evaluating the size of the
cerebellomedullary cistern, the cerebellar hemispheres
as well as the cerebellar vermis can be assessed. Within
the cerebellomedullary cistern thin septa are commonly
seen; this is a common and normal finding (Figures 16
THE CORTEX
The surface of the fetal brain at the beginning of the
second trimester is smooth and lacks gyri and sulci.
As the pregnancy reaches the third trimester, there is a
growth spurt of the fetal brain cortex. This growth spurt
results in the development of new gyri and sulci giving
the brain its typical (convoluted) appearance (Chi et al.,
1977; Dorovini-Zis and Dolman, 1977; Monteagudo
and Timor-Tritsch, 1997; Cohen-Sacher et al., 2006)

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DOI: 10.1002/pd
 DEVELOPMENT OF THE CNS BEYOND THE FIRST TRIMESTER 337

Figure 17—Using the tomographic display, serial sections through the posterior fossa are seen. Note the rounded bilateral posterior horns (PH)
of the lateral ventricle. Inferiorly the posterior fossa is imaged. C represents cerebellum

Figure 18—At 16 weeks, tomographic sections of the posterior fossa. (A) A most superior section; the marker dot (cyan) is seen over the vermis.
(B) In approximately the midsection of the cerebellum, both the cerebellar hemispheres are evident connected by the echoic vermis (in cyan the
marker dot is over the area of the vermis). (C) A most inferior section; a gap appears to be between the cerebellar hemispheres where the fourth
ventricle connects with the cisterna magna. Although, it appears that the vermis is missing, at this gestational age this is a normal finding

(Figure 19). Sonographic identification of the sulci and most active sonographic period in respect to cortical
gyri lags behind the anatomical evaluation as much development (Cohen-Sacher et al., 2006). As the gyri,
as 4–6 weeks. The 28–30 weeks of gestation is the sulci and fissures appear and deepen, there is an increase

Copyright  2008 John Wiley & Sons, Ltd. Prenat Diagn 2009; 29: 326–339.
DOI: 10.1002/pd
338 A. MONTEAGUDO AND I. E. TIMOR-TRITSCH

Figure 19—Transvaginal US demonstrating the median plane (A) At 16 weeks of gestation, the surface of the median plane is relatively smooth,
lacking any gyri and sulci. (B) At 34 weeks of gestation, the median plane of this fetus demonstrates many interlacing echoic lines which
represent the sulci

Figure 20—The insula. (A) A transabdominal scan at the level of the thalami demonstrating the insula (arrow). (B) A transvaginal scan slightly
posterior to the mid-coronal-2 or transthalamic plane demonstrating the insula

in linear bright echoes at the surface of the brain. This CONCLUSIONS

result from the echogenicity of the pia matter and the
pia arachnoid complex (soft-brain coverings).This can
best be imaged on a median section of the fetal brain.
Using transvaginal and transabdominal sonography, the
gestational age at which several sulci and fissures are
first sonographically apparent are: the callosal sulcus
from the 14th postmenstrual week; the parieto-occipital
and calcarine fissures from 18 weeks; the cingulate
gyrus and cingulate sulcus from 24 to 26 weeks.
The region of the insula and the lateral sulcus anatom-
ically appears as a linear groove at the 13th gestational
week and by 18 gestational weeks it becomes macro-
scopically identifiable. Sonographically, the area of the
insula and lateral sulcus first appears as a smooth inden-
tation on the lateral surface of the brain at around
17–18 weeks (Monteagudo and Timor-Tritsch, 1997;
Toi et al., 2004; Cohen-Sacher et al., 2006; Afif et al.,
2007). As the pregnancy progresses the shape of the
insula relative to the deepening lateral sulcus (oper-
cularization) takes the shape of an obtuse angle and
eventually an acute angle (Toi et al., 2004) (Figure 20).
As the growth spurt of the brain proceeds and opercu-
larization advances, the insula is buried by the parietal
(anterior) and temporal (posterior) opercula; this process
is not complete until term (Govaert et al., 2004).
The fetal brain compared to other organ systems con-
tinues to evolve and grow during the fetal period and
beyond. The complexity of this development results in
a variety of malformations that at times appear very
challenging to diagnose. However, we believe that the
key to correctly diagnose these malformations lie in
understanding the embryology, remembering that ges-
tational age is crucial in the development of certain
structures and lastly being very familiar with the nor-
mal anatomy of the brain in all three scanning planes.
Three-dimensional US generates volumes which can be
evaluated using a variety of planes and rendering modal-
ities will become an indispensable tool to evaluate the
developing brain.
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