European Journal of Radiology 93 (2017) 273–283

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Review

Fetal MRI of the central nervous system: State-of-the-art MARK

⁎
Lucia Manganaro , Silvia Bernardo, Amanda Antonelli, Valeria Vinci, Matteo Saldari,
Carlo Catalano
Department of Radiology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: Prenatal ultrasonographic (US) examination is considered as the first tool in the assessment of fetal abnormal-
Fetal MRI ities. However, several large-scale studies point out that some malformations, in particular central nervous
MRI system (CNS) anomalies, are not well characterized through US. Therefore, the actual malformation severity is
Prenatal CNS malformation not always related to prenatal ultrasound (US) findings.
Congenital CNS abnormality
Over the past 20 years, ultrafast Magnetic Resonance Imaging (MRI) has progressively increased as a prenatal
Fetal anomalies
CNS
3rd level diagnostic technique with a good sensitivity, particularly for the study of fetal CNS malformations. In
fact, CNS anomalies are the most common clinical indications for fetal MRI, representing about 80% of the total
examinations.
This review covers the recent literature on fetal brain MRI, with emphasis on techniques, safety and in-
dications.

1. Introduction scientific evidence [6–8].

Prenatal US examination is considered as the first tool in the as-
sessment of fetal abnormalities. However, several large-scale studies
point out that some malformations, in particular CNS anomalies, are
not well characterized through US. Therefore, the actual malformation
severity is not always related to prenatal Ultrasound (US) findings. The
divergence is due to several reasons, such as gestational age (GA), po-
sition of the fetus, type of malformation, operator experience etc. Euro-
fetus study suggests US is 88% sensitive for CNS malformations [1].
Over the past 20 years, MRI has evolved and these sequences are
increasingly being used, in particular in the study of fetal brain [2,3].
Fetal MRI is a 3rd level diagnostic tool after prenatal US, especially
when US examination is inconclusive or when a further investigation is
required, in order to confirm or improve the diagnosis and to decide on
appropriate pregnancy management. In clinical practice, fetal MRI is
also useful in parental genetic disorders and when genetic diseases af-
fected previous pregnancies [4].
In recent years, there has been an increasing interest in this tech-
nique and several articles deal with the role of fetal MRI. New horizons
are developing and some Authors are investigating on the use of 3 T
(3T), on functional studies and on three-dimensional (3D) reconstruc-
tion and segmentation of cerebral volumetry [5]. Recently, some sci-
entific societies have published guidelines and recommendations re-
garding the correct indications for fetal MRI based on clinical and
The aim of this review is to evaluate the state of art in fetal CNS MRI
and is divided into three parts: technique and protocols, safety, and
indications.
2. Search criteria
A structured search using PubMed was performed starting in April
2016 and included all relevant original and review articles published in
and after 1990. The search used the following key word combinations:
“Fetal US” AND “Fetal MRI” (> 1500); “Fetal MRI” AND “CNS
anomalies” (n = 624); “advances in Fetal MRI” (n = 181).
All papers on human subjects published were included. This yielded
a total of 805 articles. These were then evaluated for their content and
relevance to this review article; case reports were excluded. Studies
concerning MRI technical development (n = 12) were included.
Ultimately, 84 articles were deemed relevant and used as the literature
basis of this review.
With reference to these papers data, we describe imaging techni-
ques, recent developments, common clinical indications and safety is-
sues about fetal MRI.
3. Technique and protocols
In the last decade, MRI has increased its importance in the field of

⁎
Corresponding author.
E-mail addresses: lucia.manganaro@uniroma1.it (L. Manganaro), silviabernardo@live.it (S. Bernardo), amanda.antonelli@hotmail.it (A. Antonelli),
valeriavinci87@yahoo.it (V. Vinci), matteo.saldari@gmail.com (M. Saldari), carlo.catalano@uniroma1.it (C. Catalano).

http://dx.doi.org/10.1016/j.ejrad.2017.06.004
Received 10 August 2016; Received in revised form 31 May 2017; Accepted 5 June 2017
0720-048X/ © 2017 Elsevier B.V. All rights reserved.
L. Manganaro et al.
prenatal diagnosis. Fetal MRI of the CNS has to be considered as a 3rd
level examination after a 2nd level neuroultrasonography, performed
by an expert fetal neurosonographist in dedicated centres, resulted
doubtful or difficult to execute for fetal presentation or maternal ha-
bitus.
Generally, fetal MRI is performed using a 1.5T traditional super-
conducting magnet with a phased array surface coil allowing a suffi-
cient Signal-to-Noise Ratio (SNR) and an optimal imaging quality. In
most cases, the use of ultrafast imaging techniques provides good
imaging quality despite fetal motion [9], even without mother-fetus
sedation.
Phased array multi-channel coils (4–32 channels) or cardiac surface
coils can be used in relation to gestational age, size of the amniotic sac
and of the uterus. Phased array coils increase signal in the Z axis di-
rection, although still limited to around 60 cm.
Recently, some Authors have reported the potential benefits in using
stronger magnet fields (3T), nevertheless at the moment only a few
Centers use this technique in daily clinical practice. 3T imaging im-
proves SNR, when the technique is optimized. An important limitation
is represented by movement artifacts, but the development of new ac-
quisition techniques will overcome these problems [5].
Fetal MRI should only be performed after a high-quality fetal US
examination. This recommendation is based on the fact that US and
MRI are complementary imaging modalities and fetal MRI is used as a
problem-solving tool. The patient must be informed of benefits, risks
and limitations of the procedure.
The examination is recommended from 19 Gestational Age (GA).
Before 19 GA, the currently available technology cannot provide suf-
ficient spatial and contrast resolution to add diagnostic information
because the fetus is too small; furthermore, the corpus callosum or
vermis are not fully developed before 18 GA [10].
A fetal MRI study must be focused on a region of interest, either
head/neck or chest/abdomen. Total-body assessment should be per-
formed when some images show, even incidentally, radiological signs
of associated pathologies, or when a multidisciplinary team (radi-
ologist, genetist, gynecologist etc.) suspects an extra CNS involvement.
In these cases, the study should be widened, extending the MR CNS
examination to a total fetal body MR imaging.
3.1. Sequences
The study protocol includes primarily T2- and T1-weighted images
(WI); names and acronyms for these sequences vary among the MR
manufacturers [11].
T2WI fast or turbo spin-echo sequences represent the standard se-
quence for a fetal MRI examination using single Time Repetition (TR
single shot), acquiring a single slice. Commercially, this sequence is
known as Half-Fourier Acquisition Single-shot Turbo Spin Echo
(HASTE) or Single-Shot Fast Spin Echo (SSFSE) or Single-Shot Turbo
Spin Echo (SSTSE) [12]. The slice must be thin (3–4 mm) with axial,
sagittal and coronal orientation orthogonal to the organ/area of interest
to provide detailed evaluation of fetal anatomy. Thanks to single-slice
acquisition, artifacts related to fetal motion are reduced. This acquisi-
tion modality represents a compromise between spatial resolution,
contrast resolution and SNR providing a good visualization of the fetal
anatomy during all stages of pregnancy. In particular, this kind of se-
quence enhances the static fluids and structures mainly made of fluid
such as fetal brain, cavities (ventricles, nasal and oral cavities, pharynx,
trachea, stomach and proximal intestine, urinary tract, gallbladder),
lungs and amniotic fluid [13].
Breath-hold Gradient-Echo (GE) sequences with the Balanced
Steady-State-Free-Precession (b SSFP) are frequently employed (True-
FISP Siemens, BFFE Philips, Fiesta GE, etc). These sequences are useful
in all cases of excessive fetal motion causing artifacts. This sequence
uses a very short TR (< 3 ms) and is thus not influenced by motion. B-
SSFP sequences have a high spatial and a low contrast resolution and
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European Journal of Radiology 93 (2017) 273–283
with their intermediate T2–T1 signal, they are able to display fluid in
motion as hyperintense structures. For this reason, they can be used to
study the orbits, aqueduct of Sylvius and palate.
T1-w imaging with and without Fat Suppression (FS) are acquired
during breath-holding. The most important problem is represented by
acquisition time. Two different type of T1-w sequences are generally
used: GE with short TR and Time-Echo (TE) and Fast Spin Echo (FSE-
T1). FSE-T1 provides a better spatial resolution but about 20 s (s) of
apnea are required. GE yield a lower spatial resolution but require
about 14–15 s of apnea. T1 sequences can depict some fetal organs with
T1-hyperintensity, such as the pituitary gland, some structures as cortex
and myelinated fibers and allow detection of hemorrhage or fat- lesions.
However, the weak T1 contrast of the latter structures may demand
more acquisitions, making the images more sensitive to fetal motion
artifacts.
The fetal brain has a very high content of relatively ‘free’ water and
T1 sequences with FS help to enhance the contrast between myelin
(white matter) and densely packed neurons (cortex and basal ganglia)
improving the image quality even in early GA [14].
Diffusion-Weighted Imaging (DWI) and TSE Echo-Planar Imaging
(EPI) with the application of gradients oriented in three planes in space
(b0, b50, b 200, b400 and b700 s/mm2; with optimal contrast using b-
values between 400 and 700 ms/mm2) provide information on the
microscopic motion of the free and bonded water molecules. These
sequences are useful to display, with a high sensitivity, early cortical
and white-matter maturation [15–17] and also in the description of
ischemic areas within the brain [18,19]. Apparent Diffusion Coefficient
(ADC) maps are reconstructed and ADC values measured in corre-
spondence to the Region Of Interest (ROI).
Single-Shot Fluid Attenuated Inversion Recovery (FLAIR) sequences
have a low spatial resolution but they can be useful in intra-ventricular
hemorrhage or lesions.
An alternative to standard fetal T1-weighted GRE imaging, is the
inversion-recovery-prepared single-shot fast spin-echo T1-weighted se-
quence (SNAPIR): motion artifacts are less severe and less extensive
even if acquisition time is longer than GRE T1 (40 s) [20].
3.2. Study protocol
The examination is ideally performed after fasting for at least 4 h,
because in our clinical practice we noticed that hypoglycemia decreases
fetal motion [8]. The patient is placed in a comfortable position on the
table, usually in supine position, or if not tolerated (vena cava com-
pression, polyhydramnios, multiple pregnancies), left lateral position is
preferred.
In general, no sedatives are used for mother or fetus, and no contrast
agent is administered. The study protocol involves acquisition of var-
ious sequences, some of which are necessary, whereas others are op-
tionally performed according to the clinical indication.
Our protocol includes the following sequences:
- a localizer with fast sequence (generally a T2 SSFSE) using 6 mm
slices in the maternal coronal plane to identify fetal position with
respect to the mother (presentation) and determine the position of
the fetal head, spine and stomach.
- T2 HASTE images, (repetition time, TR, 1000 ms; echo time, TE,
149 ms; slice thickness 3 mm; field of view, FOV, 270 × 270 mm;
matrix 256 × 179; flip angle 150°; total acquisition time about
15–20 s) on coronal, sagittal and axial plane to evaluate cerebral
anatomy and cerebellar biometry parameters and to characterize
possible fetal malformation. The images obtained from each series
are used as scout images for subsequent sequences in order to
minimize problems of orientation related to changes in fetal posi-
tion.
- True Fast Imaging with Steady-State Precession (TRUE-FISP) se-
quences (TR 3.5; TE 1.5; slice thickness 4 mm; FOV 400 × 400;
L. Manganaro et al. European Journal of Radiology 93 (2017) 273–283

Table 1
Fetal CNS MR study protocol.

T2-W HASTE FLAIR TRUE-FISP T1-W FLASH 2D DWI

TR (ms) 1000 10,000 3,5 200 8000

TE (ms) 149 102 1,5 5 90
Slice thickness (mm) 3 4 4 4 4
FOV (mm) 270 × 270 300 × 300 400 × 400 350 × 300 420 × 300
Matrix 256 × 179 128 × 128 256 × 144 256 × 205 192 × 192
Flip angle 150° .. 60° 70° 90°
Concatenations 1 1 1 2 1
b values (s/mm2) – – – – 50, 200, 700
TI (ms) – – – – 185
Acquisition time (s) 15–20 40 15–20 30 45

matrix 256 × 144; acquisition time 40s);
- T1 FLASH 2D (fast low-angle shot) on the axial plane with and
without suppression of fat signal (TR 200 ms; TE 5 ms; slice thick-
ness 4 mm; flip angle 70°; FOV 350 × 300 mm. matrix 256 × 205;
acquisition time 30 s, divided in two concatenations during ma-
ternal apnea).
- Echo-Planar Diffusion-Weighted Imaging with gradient oriented on
the three planes (b50, b200 and b700 s/mm2; TR 8000 ms; TE
90 ms; TI 185 ms; slice thickness 4 mm; FOV 420 × 300 mm; matrix
192 × 192; acquisition time 45 s)
- FLAIR (fluid attenuated inversion recovery): TR, 10,000 ms; TE,
102 ms; thickness, 4 mm; FOV, 300 × 300 mm; matrix, 128 × 128;
TA, 40 s (Table 1).
Overall examination time is between 20 and 30 min, even in cases
where fetal motion causes several artifacts and the sequences have to be
repeated.
4. Safety
The American College of Radiology (ACR) guidelines state that
pregnant patients can undergo MRI at any stage of pregnancy.
Nevertheless, the use of MRI should be limited to cases of inconclusive
US outcome or unclear differential diagnosis [21].
To confirm this, a large study published in 2015 assessed the effects
of 1.5T fetal MRI exposure on pregnant women. No measurable adverse
effects on neonatal hearing or intrauterine growth were found in neo-
nates submitted to fetal MRI from 16 GA to term [22].
Another recent publication confirms this evidence and shows that
prenatal exposure to 1.5T MRI during the second or third trimester of
pregnancy in a cohort of healthy fetuses is not associated with dis-
turbances in functional outcomes or hearing impairment at preschool
age [23].
On the question of the maximum field strength that can be applied,
recent studies have shown that 3T can be performed safely using a very
low Specific Absorption Rate (SAR, a measure of the Radio Frequency
−RF- energy deposition, defined as power absorbed per unit mass of
the tissue, expressed in W/kg) [24].
A report published by the Canadian Task Force on Preventive Health
Care concludes that “Fetal magnetic resonance imaging is safe at 3.0 T
or less during the second and third trimesters” [7].
reported with the use of MRI; Kul et al. [28] reported an additional
contribution in 55% of CNS anomalies.
However, it must be kept in mind that the diagnostic accuracy of
prenatal cerebral imaging is not 100%, with disagreement between pre-
and postnatal imaging being observed in about 9% of cases. [29]. There
follows a list of the main indications for Fetal MRI of the CNS.
5.1. Ventriculomegaly
The first and most common indication for MRI is Ventriculomegaly
(VM) representing about 40% of the indications for fetal CNS MRI [30].
This pathology is characterized by an atrial width > 10 mm. There
are different classification systems [31]. One of the most frequently
used systems divides VM into three groups: mild (10–12 mm), moderate
(12–15 mm), and severe (> 16 mm). [30].
VM etiologies can be classified into developmental, destructive, and
obstructive pathologies. An important prognostic factor is whether VM
is isolated or associated with additional abnormalities [32] (Fig. 1).
Prenatal differentiation between isolated versus syndromic VM is cru-
cial for the prognosis [33].
Fetal MRI should be performed in severe VM (atrial width > 16
mm) and to detect associated CNS anomalies. In mild (10–12 mm) or
moderate ( > 12 to 15 mm) VM and when there are no risk factors, the
value of fetal MRI is debated [34,35].
In a large prospective multicentre study on 147 US-diagnosed iso-
lated VM, MRI found additional CNS abnormalities in 17%, and the
most frequent association was with agenesis of the corpus callosum
[36].
Parazzini et al. studied 179 fetuses with mild VM associated with
other CNS anomalies and found that MRI provided additional findings
in 19.5% [30].
Vergani and Griffiths reported a low incidence of associated mal-
formations (6%) in fetuses with mild VM [37] while Manganaro et al.
[38] pointed out that the 26.9% of borderline VM was associated with
further CNS abnormalities.
With regard to prognosis, previous studies indicated that the ma-
jority of live born children with prenatally-diagnosed isolated mild VM,
were developmentally normal [39–41]. However, fetuses with mild
isolated VM found on fetal MRI should undergo a US follow-up for
about 8 weeks from diagnosis, to control the evolution of ventricular
dilatation [42].

5. Indications 5.2. Hydrocephalus

CNS malformations are difficult to characterize before birth. In
addition to two-dimensional (2D) and 3D US, MRI is currently em-
ployed in the diagnosis of fetal CNS abnormalities, with different in-
dications and results. CNS abnormalities are the most common clinical
indication for fetal MRI representing about 80% of all examinations
requested. [25–27].
Statistically, significant improved detection rates have been
Severe isolated fetal hydrocephalus is a rare anomaly occurring in
approximately 1.6 per 10,000 births [43]. Hydrocephalus spectrum
includes primary hydrocephalus (congenital), due to abnormal devel-
opment, and secondary hydrocephalus (acquired), originating from
intracranial bleeding, infection or accompanying fetal brain tumors.
Most of the cases have been associated with stenosis/obliteration of the
aqueduct of Sylvius [44].

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Fig. 1. Two fetuses with ventriculomegaly and associated CNS abnormalities. a-c: Fetus at 20 + 4 weeks of gestation with MRI findings of Dandy-Walker malformation and ven-
triculomegaly. Sagittal (a), coronal (b) and axial (c) T2-weighted images of a fetus with hypoplasia of the vermisand cephalad rotation of the vermian remnant (white arrow), flat ventral
surface of the pons (whitearrowhead) associated with moderate dilation of the lateral ventricles (v; 14 mm) and of the IIIventricle (black line; 4 mm). There was also hypoplastic right
frontal lobe (black arrowhead). d-f: Axial (a), sagittal (b) and coronal (c) T2-weighted images of a different fetus at 19 weeks ofgestation with MRI findings of severe dilation of the III
ventricle (black line) and of the lateral ventricles (v). The corpus callosum was not visualized (black arrow). There was also a thin trunk, dorsal “kink” at the mesencephalic-pontine
junction (black arrowhead) along with agenesis of the cerebellar vermis, hypoplastic cerebellar lobes (white arrows) (Walker Warburg syndrome).

With a primary isolated fetal hydrocephalus, MRI is more useful
than US in investigating brain parenchyma damage, secondary to
ventricular hypertension and resulting in regional ischemia with altered
microenvironment of the neural cells. [45]
5.3. Midline anomalies (Corpus callosum [CC] and cavum septi pellucidi
[CSP])
Prenatal MR imaging demonstrated high sensitivity in detecting
midline malformations. Conte et al. reported 88,9% of sensitivity in the
evaluation of these pathologies [46]. Corpus Callosum Dysgenesis
(CCD) (complete agenesis, partial agenesis or CC hypoplasia) is the
second most important indication for fetal MRI; prevalence is about 1.8
per 10,000 live births and the majority are associated with other CNS
malformations [47]. CCD’s heterogeneous and uncertain prognosis
makes prenatal counseling more difficult. The main post-natal symp-
toms may vary a lot from speech delay, social behavior difficulties,
hyperactivity attention disorders, feeding problems, epilepsy or mental
retardation.
Callosal dysgenesis can be caused by different factors such as ma-
ternal alcohol use, TORCH infections and chromosomopathy, or can be
part of a mendelian condition. Genetic causes are highly heterogeneous
comparative genomic hybridization (CGH) has identified several
genomic loci involved in CCD, such as Aicardi Syndrome [48,49]
(Fig. 2).
The CC is the main commissural pathway in the brain. Beginning at
8 weeks of gestation, it assumes its final shape by 20 weeks [50]. In
view of this, caution should be exercised when evaluating the CC before
20 GA.
Routine prenatal US can detect direct and indirect signs of CCD such
as Cavum Septi Pellucidi Agenesis (CSPA), VM and colpocephaly, high
third ventricle roof and lack of pericallosal artery signal [51]. Thanks to
the high space and contrast resolution and a wide field of view, fetal
MRI is clinically helpful in US suspicion of CCD, because it is able to
confirm US diagnosis and detect additional abnormalities that fre-
quently occur along with CCD (Fig. 3).
As mentioned above CCD may be frequently associated with other
CNS malformations. This is undoubtedly the principal contribution of
MRI in the setting of CCD. MRI has been reported to detect additional
abnormalities in 22.5% of cases compared with US [52]. In particular,
cortical dysplasia (i.e. polymicrogyria) and focal cortical gyration
anomalies can be detected at a very early stage of the sulcation process
(< 24 weeks) [53,54].
Interhemispheric cysts and lipoma can occur with CCD. Lipoma of
the corpus callosum is rare and more frequently asymptomatic, but may
present with epilepsy, hemiplegia, dementia, or headaches. The degree

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Fig. 2. Female fetus at 21 + 4 gestational weeks. Coronal (a, e) sagittal (b) and axial (c, d) T2-weighted HASTE images on coronal (a, e), sagittal (b) and axial (c, d) planes found
interhemisferic cyst (d; white star), complete agenesis of corpus callosum (b; black arrowhead) severe tri-ventriculomegaly (15 mm; a, c, d; black asterisks and black line) and focal frontal
lobe cortical dysplasia (cortical bump; d, e; white circle). This findings in a female fetus are highly suggestive of Aicardi Syndrome.

Fig. 3. Fetus at 31 + 2 weeks of gestation with a vein of galen aneurysm. T2-weighted HASTE images on coronal (a), sagittal (b) and axial (c) planes show the presence of a huge vein of
galen ectasis (white arrowhead) and a hypoplastic corpus callosum (black arrowhead). The vascular malformation caused secondary destruction of corpus callosum, which is thinner than
normal at this GA.

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L. Manganaro et al.
Fig. 4. Fetus at 29 + 5 gestational weeks. T2-weighted HASTE images on coronal (a), sagittal (b, d) and axial (c) planes showed herniation of cerebellar tonsils (a, b; white arrowhead),
moderate tri-ventriculomegaly (13 mm; a, b, c; black stars), lemon sign (c), and myelomeningocele (d, black arrowhead). This ist he typical pattern of Chiari II Malformation.
of anomaly seems to be in relation with the size and location of the
lipoma. Generally, the diagnosis of lipoma can be done only in the third
trimester of pregnancy because in earlier stages of pregnancy fetal fat is
not visible on T1-WI. Two morphologic types of pericallosal lipoma
have been described on MR imaging: a Tubulo-Nodular type (round and
measuring > 2 cm) most frequent, usually anterior and associated with
extensive callosal and cranio-facial anomalies and a Curvilinear type
(thin, measuring < 1 cm in diameter), usually more posterior [55].
The most frequent subtentorial abnormalities associated with cal-
losal anomalies include Dandy Walker malformations, pontocerebellar
hypoplasia, Chiari II and rhomboencephalosynapsis (Fig. 4).
The co-occurrence of CNS and/or extra-CNS malformations (found
in 85% on autopsy) is one of the most important prognostic predictors
[35] in the prenatal diagnosis of CCD [56]. The complexity of the dif-
ferential diagnosis between isolated and not-isolated forms remains the
most important challenge. In a recent study published on 2016 in-
cluding 138 fetuses, Authors conclude no diagnosis could be established
in 67% of cases. [57] In view of this fetal MRI should be considered in
the suspicion of CCD to improve prenatal counseling and postnatal
management.
Cavum Septi Pellucidi absence is described as an isolated or asso-
ciated feature in several pathologies, with a wide variety of outcomes.
The most frequent associations are corpus callosum dysgenesis, alobar,
lobar and semi-lobar holoprosencephaly (HPE); septo-optic dysplasia
(SOD); aqueduct stenosis hydrocephalus mainly with Chiari II mal-
formation; schizencephaly; porencephaly/hydranencephaly; basilar
encephaloceles. SOD detection is complex: CSP agenesis with commu-
nicating frontal horns and mild VM, normal CC, columns of the fornix
and falx cerebry, may indicate SOD. [58]
5.4. CNS infections
Fetal MRI is useful in the detection of CNS anomalies after TORCH
infection. TORCH is an acronym meaning Toxoplasmosis, Other Agents,
Rubella, Cytomegalovirus (CMV), and Herpes Simplex. CMV infection is
the most common fetal infection with an estimated birth prevalence of
slightly less than 1% [59]. Infection may be completely asymptomatic
or cause severe lifelong neurologic impairment. It is a common cause of
mental retardation and the leading non-genetic cause of sensor neural
hearing loss. The main challenge in prenatal assessment of CMV in-
fection is accurate prognostic evaluation (Figs. 5 and 6). VM is most
commonly seen; other features include, microcephaly, ischemic-he-
morrhagic lesions, clastic lesions, subependymal cysts, intraventricular
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European Journal of Radiology 93 (2017) 273–283
synechiae, white matter signal alterations, callosal hypoplasia, sulca-
tion and gyral abnormalities, cerebellar and cisterna magna anomalies.
At MRI, anomalies of temporal lobes are indicative of congenital
CMV infection. This sign was described for the first time by Doneda
et al. [60]: temporal lobe lesions undetected at prenatal US, appeared in
37% of cases at fetal MRI. In this study, three different MR pattern are
reported: white matter hyper intensity on T2 images, temporal cysts
and dilatation of temporal horns. The latter pattern was the earliest
abnormality (20 weeks of gestation), followed by white matter hyper
intensity at T2-WI (26 weeks) and cystic lesions (30 weeks).
5.5. Ischaemic-haemorrhagic lesions
In the suspicion of ischemic-hemorrhagic lesions, MRI can have a
crucial role in the diagnosis and localization of the lesion and evalua-
tion of its extension [18] (Figs. 5 and 6).
In case of supratentorial damage, it is important to evaluate white
matter, cerebral cortex involvement and the extension of the lesion in
relation to main cerebral areas. If posterior fossa is involved, imaging
must determine if the cerebellar hemispheres and/or the vermis are
damaged. Most of the underlying causes of cerebral/cerebellar he-
morrhage can be evaluated on MRI, such as germinal matrix hemor-
rhage, vascular malformations, and congenital infections.
MRI is mandatory for such a work-up as it delineates more accu-
rately than US the different supra and infratentorial structures, whether
intra-axial or extra-axial. They present different pathophysiology and
these data are crucial to establish post-natal prognosis or the possibility
of fetal death [28].
5.6. Cortical malformations
Cell proliferation, neuronal migration and cortical organization are
the main overlapping steps in the development of fetal cerebral cortex
[56].
Migration disorders are very often related to genetic disorders [61]
even if in some cases are caused by sporadic events during the first four
months of pregnancy. There are several forms of gyration disorders
such as polymicrogyria, lyssencephaly, pachygyria, schizencephaly and
cerebral heterotopia. Lyssencephaly or agyria, is defined by a total
absence of cerebral circumvolutions and a major reduction of sulci and
fissures [62,63] (Fig. 7) and it represents the most severe neuronal
migration disorder. Pachygyria is characterized by broad based, flat,
thick and coarse gyri. Heterotopias are collections of neurons in an
L. Manganaro et al. European Journal of Radiology 93 (2017) 273–283

Fig. 5. Fetus at 22 + 1 weeks of gestation with CMV infection. Axial (a) and coronal (c, d) T2- weighted images show a hemorrhagic lesion, which is hyperintense on an axial T1-weighted
(b) image, at the level of the right occipital lobe (white arrowhead) with involvement of the occipital horn of the right lateral ventricle associated. MRI findings of associated sub-
ependymal heterotopia (white arrow) and bilateral hypoplastic frontal lobes (black arrowheads).

abnormal location, usually sub-ependymal. In polymicrogyria, nu-
merous small gyri with intervening sulci are present, which may or may
not be bridged by fusion of the overlying molecular layer of the cortex.
Schizencephaly is a grey matter cleft, extending from the ependyma to
the pial surface of the brain [64].
Several authors have reported that the ideal period to evaluate
cortical dysplasia is between 28 and 32 gestational weeks. After that
period, MRI does not allow good delineation of the sulci do to the de-
velopment of secondary gyration [65]. Some other Authors reported
earlier gestational ages to perform fetal MRI [55].
Righini described focal cortical gyration anomalies at early
formative stage (≤24 week) Four patterns were identified: wart like,
abnormal invaginating sulcus, saw tooth, and single or multiple bumps.
A thinned or blurred sub plate and intermediate zone in the site of the
focal cortical anomaly was detected in 80% of cases.
Conte and al. recently demonstrated that in the context of a large
referral fetal imaging center, with the assessment of pediatric neuro-
radiologists with > 10 years' experience in fetal neuroimaging, the di-
agnostic value of prenatal MR imaging within 25 weeks of GA is very
high, but limitations on the sensitivity regarding the early detection of
cortical dysplasia are present. A moderate sensitivity (64.7%) in de-
tecting heterotopic periventricular nodules has been found [49]. Data

Fig. 6. Fetus at 24 weeks of gestation with multiple ischaemic areas with laminar necrosis and ventricular bleeding due to CMV infection. Axial (a) and coronal T2-weighted (c) images of
a fetus with multiple ischaemic lesions, which are hyperintense on an axial T1-weighted image due to hemorrhagic infarction (b), localized on both the hemispheres (white arrowhead)
and with hypointense material inside the right ventricle due to the presence of blood. Destruction of both the cerebellar lobes with a ischaemic lesion on the right (white arrow). Same
ischaemic lesion (black arrow) at the level of the right hemisphere on a T2-weighted image (d) wich is hyperintense on axial DWI image (e) and hypointense on the ADC map (f).

279
L. Manganaro et al.
Fig. 7. Fetus at 27 + 6 gestational weeks. T2-weighted HASTE images on coronal (a), sagittal (b) and axial (c) planes found severe ventriculomegaly a, b, c; black stars) with dysmorphic
lateral ventricles and an immature gyration pattern, with the (> 1 mm; quasi-total absence of Sylvian Sulcus (a, b; white arrowhead), primary sulci formation delay and hypoplasic
frontal lobes.
are substantially in agreement with those of a previous study by Glenn
et al., which reported sensitivities of 75% and 44% in detecting poly-
microgyria and heterotopia, respectively, in fetuses younger than 24
weeks'. [65].
Cortical dysplasia associated to Tuberous Sclerosis (TS) include sub-
ependymal and cortical nodules, which are difficult to detect before 25
gestational weeks. Nodules show a typical hyper intense signal on T1-
WI [66,67].
5.7. Posterior fossa anomalies
Posterior Fossa (PF) is occupied by cerebellum and brainstem.
Normally, cisterna magna is < 10 mm. PF study is very challenging on
US, especially in the third trimester when the skull ossification could
limit US assessment of the posterior fossa structures.
With its multiplanar capabilities, fetal MRI can evaluate vermis
morphology as well as the anatomical relationship between a retro-
cerebellar cyst and fourth ventricle, which can help differential diag-
nosis with Dandy-Walker Malformation (DWM) (Fig. 1a–c).
In the evaluation of PF, fetal MRI is mandatory to examine the
position of the torcular and the orientation of tentorium cerebelli,
cerebellar lobes, vermis (axis, foliation, and morphology), biometry,
cisterna magna and fourth ventricle size.
The most frequent indications for the study of PF in this region are
the study of the vermis, especially in suspected DWM, cerebellar hy-
poplasia, cerebellar dysplasia, cerebellar hemorrhage and Chiari
Malformation (CM) [68].
5.7.1. Dandy-Walker malformation
DWM is characterized by elevated tentorium and torcular, rotation
of the vermian axis, abnormal foliation, reduction in size and altered
morphology of the vermis (Fig. 1a–c).
Fetal MRI should evaluate also the supratentorial structures, con-
sidering that the DWM spectrum is associated with supratentorial ab-
normalities such as agenesis of corpus callosum, polymicrogyria, neu-
ronal heterotopia, and occipital encephaloceles, and is associated with a
poorer clinical outcome.
On the other hand, the radiologist should also be aware of the
limitations of fetal MRI in the early gestational age, such as < 24 GA
because the vermis completes its rotation by 26 GA. For this reason, a
new radiological sign has been evaluated (the “tail sign”) to help the
diagnosis of DWM [69].
5.7.2. Joubert syndrome
The Joubert syndrome (JS) is a rare midbrain-hindbrain mal-
formation which is inherited with an autosomal recessive pattern in
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European Journal of Radiology 93 (2017) 273–283
almost all patients [70].
Fetal MRI diagnosis of JS is based on a characteristic neuroimaging
feature (Molar Tooth Sign, MTS) in which the brain stem resembles a
molar tooth on axial imaging. MTS is characterized by thickened,
elongated, and horizontally orientated Superior Cerebellar Peduncles
(SCP) and an abnormally deep interpeduncular fossa. Additional key
imaging features include partial or complete lack of the vermis on sa-
gittal imaging and a malformed fourth ventricle [71].
5.7.3. Pontocerebellar atrophy/hypoplasia
Pontocerebellar Atrophy/Hypoplasia (PCAH) are genetic conditions
with an autosomal recessive inheritance in a majority of cases.
Although a linkage to chromosome 7q11.21 has recently been identi-
fied, the molecular basis of PCAH remains largely unknown [72].
Vermian agenesis is usually associated with a poor neurological status.
The most common diagnosis associated with PCAH but with uncertain
prognosis are DWM, JS and Walker Warbourg syndrome (WWS).
In WWS (Fig. 1d–f), the cerebellum appears small and severely
dysplastic. Patients with WWS have pontine hypoplasia with a midline
longitudinal pontine cleft and cobblestone cortex, in some cases asso-
ciated with polymicrogyria in the cerebral hemispheres [73]
(Fig. 1d–f).
5.8. Twin-to-twin transfusion syndrome
Fetal MRI is especially appropriate after the death of one twin or as
a follow-up after laser therapy in order to identify possible cerebral
ischemic lesions in the remaining fetus (e.g. porencephaly) [74–76].
5.9. Neural tube defects
Neural Tube Defects (NTD) are a heterogeneous group of congenital
anomalies affecting the development of the spine early in gestation,
with an overall incidence of 1–2 per 1000 births [77].
NTD can be open (such as myelomeningocele and myelocele) or
closed and skin-covered and can be further subdivided into those with a
subcutaneous mass (meningocele, lipomyelomeningocele, lipomye-
loschisis or myelocystocele) or without an associated subcutaneous
mass (split cord; neurenteric cyst or caudal regression syndrome; filar
lipoma, tight filum terminale, persistent terminal ventricle and dermal
sinus). MRI has increasingly been used as a complementary tool of in-
vestigation when US is limited, being useful for the assessment of the
hindbrain herniation degree and the evaluation of fetal brain and spinal
cord anatomy. MRI additional information could be useful for prenatal
counseling, helping to establish if fetal surgery is a worthy option and
to plan delivery and postnatal management [78].
L. Manganaro et al.
Fig. 8. Fetus at 19 + 4 gestational weeks. MR T2-WI on coronal (a), sagittal (b) and axial (c) planes showed cleft of the primary palate and absence of cleft lip (a, c; white circles) and cleft
secondary palate. Vermian hypoplasia is also noted (b, white arrowhead), suggesting a systemic midline malformation.
Although myelomeningocele occurs usually in the lumbar region, it
can occur anywhere along the spine. In the assessment of an open spinal
dysraphism, it is crucial to look for associated abnormalities [79].
The detection of closed spinal dysraphism and vertebral abnorm-
alities without subcutaneous masses, could be challenging. In this case,
diagnostic path is complex and usually fetal MRI shows finding only in
latter gestational ages [80].
5.12. Cleft lip and palate
Cleft Lip and Palate (CLP) is the most common facial malformation,
having an incidence of around 1/700 live births [81]. Routine fetal MRI
for CLP do not appear to be justified clinically [82]. (Fig. 8) There are,
however, circumstances in which a MRI may provide significant addi-
tional information as in complex, bilateral clefts or in cleft cases in
which there is significant risk of associated brain anomalies [83]. In
fact, this malformation can occur isolated or associated with genetic
syndrome and CNS malformations (VM or midline malformation, i.e.
holoprosencephaly) [84].
6. Conclusion
The clinical interest on fetal MRI in prenatal diagnosis as a third
diagnostic tool is increasing, especially in the assessment of CNS mal-
formations, due to the high spatial resolution and for the opportunity to
detect associated fetal brain and body anomalies. If a complex mal-
formation is suspected, fetal MRI could be crucial to identify and
characterize CNS lesion, being helpful for prenatal counseling and
pregnancy management. Moreover, new horizons are developing and
some Authors are investigating new possibilities, such as the use of 3 T
(T) and functional CNS studies.
Conflict of interest
There are no conflicts of interest by none of the authors.
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