is currently Chief Resident in the Department of Diagnostic
Radiology, Yale University School of Medicine, New Haven, CT. She
earned her ScB in Neuroscience from Brown University, her MMS in
History of Medicine and Pharmacology from Brown Graduate School,
and her MD from Brown Medical School, Providence, RI. She will
begin a fellowship in women's imaging at Brigham and Women's
Hospital in Boston, MA, in July 2005.
The use of magnetic resonance imaging (MRI) to visualize a fetus
in utero was first reported in 1983.
Initially, fetal MRI was largely limited to imaging of the central
nervous system (CNS). More recently, however, technical advances
have made possible MRI of in-tratho-racic abnormalities. These
developments have paralleled advances in fetal and neonatal surgery
for thoracic pathologic conditions, which have increased the
relevance and utility of MRI. While ultrasound remains the mainstay
of fetal imaging, it is sometimes technically limited by small
field-of-view, maternal obesity, oligohydramnios, and obscuration
of fetal anatomy due to a vertex lie position late in pregnancy.
This article will discuss technical developments that have expanded
the role of MRI in prenatal diagnosis of thoracic abnormalities,
thereby facilitating treatment and patient counseling. Several
representative thoracic abnormalities will be discussed
specifically with respect to the impact of fetal MRI on diagnosis
Early limitations of fetal MRI
Fetal MRI was initially limited by technical factors.
Conventional spin-echo and gradient-echo sequences were slow and
produced relatively low-resolution images. Imaging times were
reduced by echoplanar techniques and initially applied to fetal
but images suffered from susceptibility and chemical shift
artifact, low signal-to-noise ratio (SNR), poor spatial resolution,
and the need for special hardware.
Although several early reports described fetal anatomy,
MRI in the pregnant patient was mostly limited to evaluation of
maternal anatomy such as pelvimetry
and pelvic masses complicating pregnancy.
Early fetal MRI was most useful in delineating CNS anomalies found
on ultrasound, particularly later in pregnancy when ossification of
the fetal skull and fetal vertex lie limited visualization by
ultrasound. Early attempts to reduce fetal motion during long pulse
sequences included neuromuscular blockade or sedation. Pancuronium
bromide was administered to the fetus by intramuscular or umbilical
vein injection, but this was abandoned due to impracticality of
umbilical vein access. Oral diazepam was also given to the mother
in an effort to reduce fetal motion.
Technical advances in fetal MRI
In the 2 decades since the first reported use of fetal MRI,
increased availability of high-field-strength systems and new pulse
sequences have made possible dramatic improvements in fetal
imaging. Since the 1990s, fetal MRI has primarily relied on
variants of the rapid acquisition with relaxation enhancement
(RARE) technique for fast T2-weighted imaging. These include
single-shot fast spin-echo (SSFSE; GE Healthcare, Milwaukee, WI)
and half-Fourier acquisition single-shot turbo spin-echo (HASTE;
Siemens, Erlangen, Germany).
A few technical considerations are helpful to illustrate recent
improvements over previous pulse sequences. SSFSE and HASTE use a
single radiofrequency pulse to excite a tissue slice with multiple
phase- encoding steps. Because the repetition time (TR) is
essentially infinite, heavily T2weighted images are produced that
are particularly well-suited to imaging fluid-filled fetal
structures. Each slice can be obtained in <1 second, thereby
minimizing motion artifact. Images are usually acquired using
single-slice technique instead of interleaved multislice technique.
Slices are usually acquired in 5-mm intervals. Aflip angle of 150°
may be used to improve SNR, and angles >150° may be avoided to
decrease the specific absorption rate (SAR).
Most protocols obtain T2-weighted SSFSE-type images in 3 planes,
often oriented with respect to the fetal body axis. Coakley and
recently pro-vided a sample protocol for fetal MRI.
T1-weighted images are obtained primarily for the visualization
of fat and hemorrhage, plus special applications like spectral
water suppression to evaluate the skeletal system.
Most protocols use spoiled-gradient echo imaging limited to the
area of clinical interest.
High-field (3T) magnets, parallel imaging, and real-time imaging
are recent developments in MRI technology that have potential
benefits for fetal imaging. Improved SNR and higher spatial
resolution afforded by new 3T magnets could improve visualization
of small fetal structures and, possibly, shorten imaging time.
Unfortunately, depending on implementation, SAR deposition may
increase at 3T, which is an especially important consideration for
fetal imaging. Several of the currently used modifications to
reduce SAR deposition, such as limiting total number of slices and
reducing flip angle, will likely prove useful in implementing 3T
systems in fetal MRI examinations. Parallel imaging offers faster
image acquisition with the potential benefit of SAR reduction.
McKenzie and colleagues
reported im-proved quality of fetal MRI images via increased SNR
efficiency strategy in array spatial and sensitivity-encoding
technique (ASSET; GE Medical Systems), a form of parallel imaging.
Levine and colleagues
recently described the use of real-time single-shot fast spin echo
(RT-SSFSE) in fetal MRI. In this technique, SSFSE images are
obtained through a prescribed region-of-interest, and image
reconstruction is available nearly immediately after acquisition of
a single slice. They reported improved orthogonal views with
respect to the fetal body axis and increased SNR due to re-duced
cross-talk (as occurs when multiple slices are obtained at the same
Technical and safety considerations
Patients may be positioned feet-first within the magnet to
minimize claustrophobia. Maternal sedation is rarely needed; oral
or sublingual diazepam may be used if necessary. Fetal sedation is
no longer commonly used. Fasting for 4 hours prior to the
examination helps reduce postprandial bowel peristalsis.
Examinations are best performed after 20 weeks' gestation for
several reasons. First, there is better conspicuity of fetal
anatomy as the fetus gets larger. Second, most examinations are
prompted by abnormal findings from the prenatal ultrasound
examination, usually performed at approximately 20 weeks. Third,
timing of the study is important to determine its clinical utility.
Termination of pregnancy and fetal surgery are time-dependent
in-terventions. Fetal surgery is usually performed between 26 and
29 weeks, and imaging is best obtained in close proximity to the
time of surgery because the second trimester is a period of rapid
growth and change.
has advocated for the use of an ultrasound examination immediately
preceding MRI, to show change or even resolution of an anomaly
diagnosed on a previously performed ultrasound, to narrow the
differential diagnosis, or rarely, to detect fetal demise that
obviates the need for fetal MRI.
Although no known risk exists for either fetus or mother, no
prospective human trial has been conducted to prove the safety of
fetal MRI, and written consent may be obtained prior to performing
the examination (this practice varies in different locations).
Theoretical risk during organogenesis ordinarily limits the use of
fetal MRI to the second and third trimesters. Gadolinium is not
required for fetal MRI but may be used for maternal indications if
the benefits are felt to outweigh the risks.
Gadolinium presents a theoretical risk to the fetus due to
dechelation and the release of free gadolinium within the amniotic
fluid and fetal circulation. Nevertheless, no adverse effect on
fetal mice was found when gadolinium was administered to pregnant
Discussion of the risks and benefits with the patient is of
Fetal MRI in the evaluation of thoracic
Because the fetal lungs are fluid-filled, they are easily
visualized on T2-weighted sequences (Figure 1), and with the advent
of faster sequences, they have been the subject of much research.
Pulmonary hypoplasia is defined as lungs that are too small in size
for the gestational age, and it may result in neonatal respiratory
distress and occasionally death. Causes include intrathoracic
masses, oligohydramnios, neuromuscular dysfunction, or
abnormalities of the bony thorax. Rarely, it may be primary.
Estimation of fetal lung volume has previously relied on thoracic
circumference measurements on ultrasound and comparison to
nomograms to predict lung development.
This method indirectly measures fetal lung volume and may be less
accurate for fetuses with intrauterine growth retardation. The
development of fast T2-weighted sequences has enabled researchers
to directly measure fetal lung volumes with good success. MRI
provides greater resolution of lung tissue from surrounding
soft-tissue structures than does ultrasound and thereby may
facilitate more accurate measurements. Coakley and colleagues
used RARE sequences to measure fetal lung volumes and found
excellent correlation with biometric measurements obtained by
ultrasound. Recently, Osada and colleagues
reported that quantitative lung volume measurements on MRI
correlated directly with clinical outcome. Research is ongoing to
ascertain whether MRI can play a role in the evaluation of
intrinsic lung properties such as relaxation time, which may
predict the degree of lung maturity.
Congenital diaphragmatic hernia
Congenital diaphragmatic hernia (CDH) is caused by a defect in
the diaphragm, allowing herniation of abdominal viscera into the
thorax (Figure 2). CDH occurs in approximately 1 in 1000
pregnancies and in 1 in 3000 to 4000 live births. The diaphragm
forms from 6 to 14 weeks of gestation; CDH can occur at different
times during gestation and has a poorer prognosis with earlier
The diagnosis has traditionally been made on ultrasound upon
visualization of intra-abdominal contents above the diaphragm. The
diaphragmatic defect itself is occasionally visualized on MRI: 80%
are left-sided (of which 57% to 86% are associated with concomitant
liver herniation, so-called "liver up" CDH; the remainder lack
liver herniation and are termed "liver down") and 20% are
right-sided (all of which are "liver up" by definition); 3% are
bilateral (which is fatal); and 92% are posterolateral,
corresponding to the foramen of Bochdalek.
Mortality has been reported as 50% to 68% overall; mortality is
higher for liver-up CDH (57%) than liver-down CDH (7%).
Approximately one third have associated abnormalities (cardiac,
spinal, trisomies) and have an associated higher mortality rate
CDH causes pulmonary hypoplasia and, if large enough, may compress
the mediastinum and result in obstruction of venous return and
hydrops. Early attempts at reduction of liver herniation with in
utero surgery were unsuccessful due to obstruction of the ductus
venosus and resultant fetal demise.
Subsequent development of in utero tracheal occlusion via
fetoscopic approach has been successful for some fetuses; this is
thought to reduce the CDH by increasing pressure within the
developing lung and thorax and encourages lung development via
alveolar hyperplasia. The affected lung remains relatively
deficient in surfactant, however, and the fetus is at risk for
neonatal respiratory distress syndrome.
On ultrasound, CDH can present a diagnostic dilemma because lung
tissue is similar in echotexture to liver; thus, liver position may
be difficult to determine on ultrasound. Indirect signs of CDH on
ultrasound include posterior displacement of the stomach with
liver-up, left-sided CDH
and supradiaphragmatic displacement of the portal and hepatic veins
on Doppler ultrasound.
Success in diagnosing CDH on ultrasound is variable: for example,
in 92 fetuses diagnosed with CDH, the diagnosis was missed on
prenatal ultrasound in 44 (48%).
In contrast, liver tissue is easy to differentiate from lung tissue
on MRI because the lung is hyperintense on T2-weighted images and
the liver is hypointense (and vice versa on T1-weighted images).
Bowel is also hyperintense on T2-weighted images but can be
distinguished from the homogeneous pulmonary pa renchyma due to the
excellent soft-tissue resolution afforded by MRI.
Several studies have shown equal or greater accuracy of MRI
diagnosis of CDH compared with ultrasound (Table 1).
In cases where MRI and ultrasound were equally efficacious at
diagnosing CDH, MRI may more completely define the anatomy. In one
study, MRI was judged to have provided additional anatomic detail
in 14 fetuses in whom CDH was diagnosed on both ultrasound and MRI
(11 of which were liver-up).
The larger field-of-view afforded by MRI can also show additional
abnormalities that affect the fetus's prognosis and potential
eligibility for fetal surgery. MRI readily facilitates
differentiation of liver-up and liver-down CDH, which is important
for prenatal counseling due to the much poorer prognosis for
Liver position also determines eligibility for in utero tracheal
occlusion surgery (selection criteria for in utero tracheal
occlusion surgery are provided in Table 2).
Although Levine and colleagues
reported 100% concordance between ultrasound and MRI in determining
liver position, lower success rates have been reported by other
Comprehensive visualization of anatomy can help physicians and
patients anticipate a need for birth at a tertiary care center and
thus facilitate prenatal planning. For example, Huppert and
reported a case of a right-sided CDH that was seen on MRI (but not
ultrasound) and prompted referral to a tertiary care center for
MRI helps to distinguish CDH from other intrathoracic masses
that may be indistinguishable on ultrasound. For example, a
left-sided liver-down CDH may be differentiated from a cystic mass,
such as cystic adenomatoid malformation, due to the hyperintensity
of these entities on T2-weighted images. In one article, 2
right-sided and 1 left-sided CDHs were misdiagnosed as congenital
cystic adenomatoid malformations (CCAMs) on ultrasound but were
correctly identified on MRI.
Finally, MRI may be useful for volumetric measurements of the lungs
to predict, although further research is needed to better define
the role of MRI volumetry.
In summary, the best role of MRI in prenatal diagnosis of CDH is
probably in identifying liver position and differentiating CDH from
lesions that appear similar on ultrasound.
Congenital cystic adenomatoid malformation
A cystic mass formed by abnormal proliferation of bronchioles
(Figure 3), CCAM comprises 25% of congenital lung lesions, is
usually unilobar, and is not usually associated with other
Three types are classified according to cyst size: type 1
(macrocystic), type 2 (intermediate), and type 3 (microcystic).
All lesions should be resected postnatally due to the risk of
recurrent infection and carcinomatous transformation. Macrocystic
CCAMs usually have a benign course and are resected postnatally.
Rarely, these can exert mass effect and cause hydrops;
thoracoamniotic shunting may be used if the lesion is composed of a
single large cyst. Microcystic CCAMs are more likely to cause in
utero complications; in utero lobectomy or pneumonectomy may be
performed if the fetus is <32 weeks' gestational age, or
emergent delivery (with anticipation of postnatal respiratory
distress) may be advocated after 32 weeks' gestation.
Ultrasound appearance of CCAM varies according to the size of
the cysts. On ultrasound, CCAM can be misdiagnosed as CDH; the
microcystic form appears as a solid mass and mimics a liver-up CDH,
and the macrocystic form may mimic loops of aperistaltic bowel in a
All CCAMs are hyperintense relative to lung parenchyma on
T2-weighted images, but not as hyperintense as amniotic fluid.
MRI helps to differentiate the macrocystic form from fluid-filled
loops of bowel in CDH by excluding a diaphragmatic defect that
would be seen in CDH and better outlining the diaphragmatic contour
(convex on the abdominal side in the case of CCAM) than on
Numerous entities have been reported in the literature as having
been misdiagnosed as CCAMs, including CDH, tracheal atresia,
pulmonary agenesis, neurenteric cyst, bronchial stenosis, and
In a study by Hubbard and associates,
out of 18 patients, 16 of whom were originally diagnosed with CCAM
on ultrasound, 9 were subsequently diagnosed with CCAM on MRI (8 of
which were concordant on pathology; 1 thought to be CCAM on MRI was
ultimately diagnosed as bronchopulmonary sequestration). Not only
does MRI make a more conclusive diagnosis of CCAM, it may also be
used in the future to calculate lung volume and growth after fetal
surgery if required in the setting of hydrops.
Bronchopulmonary sequestrations (BPSs) are foregut malformations
in which lung tissue develops without connection to the normal
bronchial tree, most commonly found in the posterolateral lower
lobes (Figure 4). Arterial supply is systemic, usually from the
aorta or celiac artery. Seventy-five percent are intralobar, with
venous drainage via the pulmonary veins; 25% are extralobar and
contained in their own pleural investment, with most venous
drainage occurring via the inferior vena cava or azygos systems
(25% via the pulmonary veins). Ten percent of extralobar BPSs are
subdiaphragmatic and may or may not communicate with the
gastrointestinal tract. Most occur in isolation, although a
minority may occur in association with other foregut abnormalities
and/or CDH. Extralobar BPSs are more likely to be detected
prenatally than are intralobar sequestrations. While BPSs usually
regress during gestation, follow-up is recommended because they may
increase in size and cause hydrops; this complication is much more
common with extralobar than intralobar BPS. Postnatal complications
include hemoptysis and recurrent infection.
On ultrasound, BPS appears as a well-demarcated, wedge-shaped,
echogenic mass; ultrasound uncommonly shows the systemic feeding
artery. MRI shows BPS as a well-defined, uniformly hyperintense
mass on T2-weighted images that is just below the signal intensity
of surrounding amniotic fluid. Over time, regressing BPS may appear
A unilateral pleural effusion may be seen with extralobar BPS. When
subdiaphragmatic, BPS may be confused with congenital neuroblastoma
or adrenal hemorrhage on ultrasound.
MRI helps to distinguish between these entities because hemorrhage
is hyperintense on T1-weighted MR images, whereas BPS will be
hypointense. BPS is homogeneous on MRI compared with the
heterogeneous appearance of neuroblastoma.
This feature also helps differentiate it from a macrocystic CCAM
and CDH, both of which are heterogeneous. The primary role of MRI
in diagnosis of BPS is differentiating it from other lesions that
are more likely to require in utero treatment, and also may be
beneficial for follow-up to monitor for growth and development of
hydrops. Treatment of BPS is indicated if hydrops or other
complications develop and is similar to that performed for CCAM, as
Miscellaneous intrathoracic abnormalities
Other miscellaneous intrathoracic lesions have been
characterized on MRI, including congenital high airway obstruction
(CHAOS), in which there is intrinsic tracheal obstruction. CHAOS
can be detected prenatally on MRI because the fluid-filled airways
are hyperintense on T2-weight-ed images, the lungs appear
distended, and the diaphragms are everted due to increased
A similar appearance may be seen with tracheal or bronchial
atresia. The fetus is at risk of respiratory distress and/or death
at birth because of an inability to aerate the lungs; the fetus may
require delivery via the ex utero intrapartum treatment (EXIT)
procedure. In EXIT, the fetus is partially delivered and the airway
secured before disconnection from the placental circulation, or the
fetus may immediately begin extracorporeal membrane oxygenation
(ECMO). Cystic hygromas can extend into the chest and mimic cystic
lung masses; the wider field-of-view of MRI helps show extension
from the neck, and the lack of soft-tissue nodularity helps exclude
similarly appearing cystic masses such as teratoma.
Neck masses with intrathoracic extension are well evaluated by MRI
for better depiction of the extent of anatomical involvement.
Neurenteric cyst, foregut duplication cyst, mediastinal
lymphangioma, bronchogenic cyst, and congenital lobar emphysema
have also been described on MRI imaging of the fetal chest.
Prenatal diagnosis of a bronchogenic cyst was correctly made on MRI
(ultrasound suggested CCAM or sequestration), and EXIT procedure
was successfully per-formed.
The role of MRI in diagnosis and treatment of in utero
intrathoracic pathologic lesions is still being defined. Certainly,
ultrasound will remain the mainstay of fetal imaging. MRI offers
several technical advantages over ultrasound, including a larger
field-of-view, less limitation due to maternal habitus, and ability
to visualize fetal anatomy regardless of fetal presentation. Fetal
MRI may provide information in addition to that from ultrasound and
may affect care of fetuses in whom intra-thoracic pathologic
lesions have been diagnosed (Table 3).
Developments in fetal surgery, such as temporary tracheal occlusion
for CDH, EXIT procedure for CHAOS, and in utero resection of CCAM,
all benefit from the superior anatomical depiction and mass
characterization that MRI offers. Less quantifiable, but perhaps
even more important, is the greater ease of recognition of anatomy
that MRI provides that facilitates patient counseling and
consultation with referring clinicians. MR spectroscopy of the
lungs and volumetric assessment of pulmonary hypoplasia are just 2
of many future research developments on the horizon.