Donald School Journal of Ultrasound in ObstetricsM Lituania andet al Gynecology, July-Sept. 2007;1(3):60-76 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

1M Lituania, 2MP Fondelli, 1U Passamonti, 2L Saitta, 2A Cerchiaro, 2T Arcuri

1SS Medicina Fetale e Perinatale, Dipartimento di Scienze Genetiche, Perinatali e Ginecologiche, EO Ospedali Galliera - Genova 2SC Neuroradiologia e Radiologia Interventistica, Dipartimento di Neuroscienze e Cardio-vascolare, EO Ospedali Galliera – Genova

Correspondence: Lituania Mario, Via Ippolito D’Aste 3/7, 16121 Genova, Italy Mail: [email protected], Tel. +39-010-561961, Fax: +39-010-57481068

Abstract: Even if ultrasonography still remains the primary prenatal of the fetal head, advanced skull ossification). The absence of investigation technique for the assessment of fetal development, bone artefacts allows to accurately evaluate the magnetic resonance imaging (MRI) plays an important role for the and the overlying subarachnoid spaces. Moreover the study of fetal morphology and pathology. reproducibility of the technique makes it possible to repeat the MRI has been shown to be particularly useful for the evaluation examination every time a pathologic condition needs to be of the central (CNS), the latter being a common site of monitored in time. pathology such as cerebral and spinal malformations. MRI is contributive in defining fetal neck, thoracic, abdominal, Although the harmlessness of MRI still has to be proven and pelvic masses. This can be especially helpful when differing and no harmful effects are described so far on the fetus (studies opinions exists as to the etiology of a mass. on potential harmful effects on the fetal hearing depending on Ultrasonography, a non invasive, low cost, real time technique, the scanner noisiness are in progress), fetal MRI is usually still represents the investigation of choice in prenatal screening, not performed as a second choice investigation,15 when indicated only regarding the CNS. Nevertheless several cases need a diagnostic by the sonographer, only starting from 18 weeks of pregnancy, complement by means of MRI, that increases the diagnostic potential the fetal morphogenesis being ended and the fetal dimensions of ultrasound . allowing to obtain a sufficient spatial and contrast resolution. The additional information from MRI is important in prenatal The disadvantages of MRI mainly depend on the high costs counseling, delivery planning and planning for pre- or postnatal (that considerably overcome those of ultrasonography), on the intervention. scant literature related to its relatively recent applicability and Key words: Magnetic resonance imaging, congenital anomalies, prenatal which is limited to a few ultraspecialistic centers and on the diagnosis, pregnancy, fetus. scarcity of controlled studies, especially referring to fetal lesions acquired during late pregnancy. INTRODUCTION Even if ultrasonography still remains the primary prenatal Technique investigation technique for the assessment of fetal development, The need for eliminating fetal and maternal movements in order nowadays magnetic resonance imaging (MRI) plays an important to obtain images of sufficient diagnostic quality has been 1-7 role for the study of fetal morphology and pathology. MRI representing a sometimes insurmontable limit to perform fetal has been shown to be particularly useful for the evaluation of MRI. Fetal sedation by means of curare used to be indispensable 8-14 the central nervous system (CNS), the latter being a common during the first clinical applications of MRI because of the length site of pathology such as cerebral and spinal malformations of spin echo sequences lasting 4 to 10 minutes. When such that are frequently detected on prenatal screening ultrasound. invasive techniques were abandoned fetal immobility was later Due to its easiness to perform and possibility of producing obtained by either oral or intravenous administration of multiplanar images and obtaining easy-to-reproduce anatomical benzodiazepines to the mother. Thanks to the advent of ultrafast planes, MRI represents the investigation of choice in imaging (echo planar and single shot fast spin echo techniques), sonographic uncertain cases or in some fetomaternal conditions high definition images of the fetus can now be obtained in less that may hinder a correct visualization of the fetus by means of than one second with no need for invasive techniques and ultrasound (maternal obesity, oligohydramnios, low position thus eliminating the problem of fetal movements; T1-weighted

60 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations sequences only still require relatively long acquisition times (echo planar imaging) can visualize the cytotoxic and/or (about 18 seconds) and remain sensitive to fetal and maternal vasogenic edema resulting from recent ischemic lesions, and movements. Ultrafast imaging is a prerogative of high field they can furthermore provide important informations for the magnets and highly performing gradients. The combination of evaluation of pre-myelinated white matter bundles and cortex, 1.5 T magnets and multiple torso/phased array coils is associated earlier than with conventional sequences. The purpose of with high signal homogeneity and very good spatial and contrast diffusion tensor imaging is to study the water diffusion within resolution both in fetal brain and spine. the cerebral tissue by measuring the apparent diffusion The MRI examination is performed, after centering the coefficient (ADC) and the fractional anisotropy (FA). For this anatomical region of interest, both with T1-weighted (T1W) purpose multishot echo-planar imaging (EPI) techniques with and T2-weighted (T2W) sequences, acquired while the mother diffusion gradient (amplitude: 30 mT/m, b: 600 s/mm2) are applied is freely breathing on the three spatial planes according to the in six non-collinear axis to obtain transverse sections of the fetal anatomy. To study the brain and the , contiguous fetal brain (acquisition time of about 1 minute). The parameters slices respectively 3 and 2 mm thick are obtained, with no gap ADC and FA are then measured in different anatomical regions, interposition. such as the corpus callosum, the frontal white matter, the basal The good quality of images is favored by the cephalic ganglia, the cerebral peduncles. presentation of the fetus, a condition in which the transmission MR spectroscopy,17 even though successfully applied, requires of maternal respiratory movements to the fetal head is reduced. fetal immobility through maternal sedation, resulting in non- Ultrafast T2W sequences (single shot FSE), thanks to the routinary application. Spectroscopic studies are based on the excellent signal to noise ratio (SNR) and the extremely good variation of the resonance frequency of a nucleus according to contrast resolution (depending on the high water content of the molecular structure. Hydrogen, consisting of one proton fetal brain), represent the basis of fetal MRI; such sequences only, is the most studied nucleus. It is possible to determine the are primarily meant to outline the anatomy and to study the concentration of several biologic molecules contained in a given cerebral sulci, besides being useful in biometric analysis. Each tissue by studying the amplitude of the different spectroscopic individual slice is acquired separately with a duration of about frequencies emitted by a small volume of such tissue. The 400 ms, so that these sequences are not particularly affected by molecules of interest in the CNS include: N-acetyl-aspartate (a fetal movements. New generation MRI equipments allow to marker of neurons and axons density), creatine (a marker of perform 3D T2W acquisitions with a substantial reduction of cellular metabolic energy), coline (a marker of cell membrane the examination time. Several anatomical structures such as the integrity and myelination) and lactate (a marker of anaerobic corpus callosum, the cavum of the septum pellucidum, the metabolism). vermis and the cerebellar hemispheres can be easily pointed A spectroscopy pattern showing reduced N-acetyl-aspartate out by T2W sequences. On the other hand there are lesions, levels and increased lactate levels is highly suggestive of such as small calcifications and some types of hemorrhagic impaired neural development. lesions, and the cerebral myelination pattern that they cannot Functional MRI18 is a relatively new technique which gives accurately assess. information on the pre- and poststimulus blood flow to various Fast gradient echo sequences with low flip angles are used parts of the brain. When an external stimulus causes increased to obtain T1W images. They are characterized by longer neuronal activity in one part of the brain there is increased acquisition times than the former sequences and they are often blood volume to this site. Functional MRI can identify the brain sensitive to movement artefacts; also they are less indicated response to various stimuli by estimating the amount of for the study of the cerebral anatomy, but they find indication oxyhemoglobin in venous blood at different sites. This in the evaluation of cerebral myelination, in the detection of technique may allow to identify fetal brain dysfunction even in intra and pericerebral hemorrhage, calcifications (subependimal absence of anatomical anomaly. nodules of tuberous sclerosis), lipomatous tissue (corpus Since gadolinium is able to pass through the placental callosum lipomas). filter entering repeatedly the fetal circulation, paramagnetic Gradient echo T2* sequences are able to depict hemosiderin contrast agents are not at the moment used in fetal MRI. deposits and calcific tissues as areas of signal loss, due to paramagnetic interferences; also they easily outline osseous Examination Protocol and osteocartilaginous structures: nevertheless these sequences have a low SNR with a poor definition of the anatomy Fetal MRI is performed by a standardized protocol, by using 4- and of the cerebral parenchyma. 5 mm thick slices orientated parallel and perpendicular to the brainstem. If necessary the examination can be complemented Angiographic images can be obtained when suspecting a with more slices of lower thickness aimed to the region of interest vascular malformation.16 Diffusion weighted images (DWI) orientated in the different spatial planes.

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CNS Normal Anatomy occipital fissure, calcarine fissure). The hippocampal fissure and the collateral and external occipito-temporal sulci are better The normal anatomy of a developing fetal brain is characterized identified in coronal sections, as well as the superior and inferior by considerable morphologic changes involving the volume temporal and occipital sulci and the intraparietal sulcus. The and shape of the ventricles, the contraction of the pericerebral Sylvian fissure and its opercularization are evaluated in the liquoral spaces, the reduction of the germinative matrix, the three orthogonal planes. development of cerebral sulci. The gyration pattern becomes Study of myelination: cerebral myelination can be assessed in almost completely visible only at gestation week 34-35. axial sections by T1W sequences where it shows high signal Subarachnoid spaces usually remain wide, especially in the intensity. Myelination of several structures can be evaluated:20 parieto-occipital region. The maturation process underlying the pons tegmen, the cerebellar vermis and cerebral peduncles, neuronal migration and cerebral myelination is characterized by the internal capsule and basal ganglia. DWI can also be used. several MR signal changes occurring simultaneously.19 Such changes reflect modifications in the water content and cellular CNS Anomalies density, especially evident in the brainstem at gestation week 20, of the germinative matrix and of the white matter, where the Ventriculomegaly: is defined by the evidence of a ventricular intermediate zone formed by migratory neurons can be visible atrium width of more than 10 mm and it can have a malformative, until week 30. obstructive or clastic origin (Fig. 1). In 70-84% of cases is MR signal changes can be already identified at 20 weeks of associated with chromosomal anomalies and with other organs pregnancy in the posterior limb of the internal capsule and in and CNS malformations (neural tube defects, agenesis of the the optic tracts, and in the semioval centers at gestation week corpus callosum, Dandy-Walker malformation, cortical 35. Considering MR analysis, it is important to point out how dysplasias, gyration anomalies). It can also be associated with the normal multilaminar presentation of fetal brain and the subependimal and intraventricular hemorrhages and regular sequential appearance of the fissures and cerebral sulci . The prognosis of isolated ventriculomegalies is represent essential parameters of a normal CNS development. favorable, while in case of ventriculomegaly with associated On the other hand when such patterns are modified, they can CNS malformations the probability of late psychomotor be sign of severe pathologic events. development increases. The detection of the latter is therefore Fetal MRI should be essentially considered as a of critical importance and fetal MRI represents the reference complementary and supplementary investigation technique in technique for such purpose: the literature reports that fetal MRI the assessment of the fetus in the second and third trimester, has detected CNS malformation associated with particularly when facing ultrasonography limits and doubtful ventriculomegaly in 40-50% of the cases and such anomalies cases. were not previously diagnosed by ultrasonography (Fig. 2). Fetal biometry on MRI20-22 is strictly related to Agenesis of the corpus callosum. Complete or partial, this ultrasonographic biometry and it can be used to obtain malformation has been reported both in asymptomatic patients supplementary information on the fetal CNS. A biometric study and in association with various neurological deficits includes the measuring of several anatomical structures, for (psychomotor delay, epilepsy). In about 85% of cases it is example: fronto-occipital diameter, biparietal osseous and associated with other CNS malformations, such as Dandy- cerebral diameter, corpus callosum length, lateral ventricles, III Walker, Chiari II, cortical dysplasias, oloprosencephaly, and IV ventricles, interhemispheric distance, anteroposterior and cranio-caudal interopercular distances, vermis height and anteroposterior diameter, vermis surface, transverse cerebellar diameter. Such measures are obtained directly during the examination and then compared to statistical data. The study of gyration20,23 aims to the assessment of the sulci. They can only be called sulci when they are clearly identifiable as real depressions on the cerebral surface. Cerebral sulci are divided into primary and secondary, the latter arising as ramifications from the first and being more easily assessed in later stages of the fetal development. The central, pre and postcentral sulci can be studied in axial sections at the vertex. The sulci of the internal surface and of the basis of the cerebral Figs 1A and B: Bilateral ventriculomegaly at 26 weeks of pregnancy. hemispheres can be better assessed in sagittal and coronal Symmetrical dilatation of the lateral ventricles; cavum septi pellucidi sections (cingulate sulcus, marginal, callosal, internal parieto- and cavum vergae (A and B) axial sections

62 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

Figs 3A and B: Agenesis of the corpus callosum at 33 weeks of pregnancy. Parallel course of the lateral ventricles, with colpocephalic configuration, telencephalic pseudocyst and eversion of the cingulate Figs 2A and B: Untreated Toxoplasma infection at 31 weeks of pregnancy. with small iuxtaependymal cysts (arrow). Slight expansion of the periencephalic liquoral spaces. (A and B) axial and coronal sections, but above all it allows to detect the sections absence of the corpus callosum besides the possibly associated ultrasound invisible CNS anomalies. cephalocele, , Aicardi’s syndrome. Callosal The posterior fossa malformations that can be diagnosed agenesis can now be diagnosed by ultrasound, both with by fetal MRI include the Dandy-Walker complex (Dandy-Walker indirect signs and with a direct visualization of the lack of the malformation and Dandy-Walker variant), the mega cysterna corpus callosum. magna, the Blake’s pouch, arachnoid cysts, cerebellar In some cases of partial agenesis and/or of inadequate malformations (hypoplasia and dysplasia), and the Chiari II visualization of the corpus callosum caused by malformation. oligohydramnios or maternal obesity, the diagnosis can only In the Dandy-Walker malformation MRI shows a cystic be confirmed by a fetal MRI examination. Sometimes a dilatation of the IV ventricle, a widening of the posterior fossa particularly flexed or deflexed position of the fetal head and with high confluence of the sinuses, a hypoplasia or agenesis some positions of the maternal pelvis make a fetal MRI necessary of the inferior cerebellar vermis, which appears anticlockwise to complement an ultrasonographic suspect. Ultrasonographic rotated (Figs 4 and 5) . In the Dandy-Walker malformation variant, suspicious findings can be represented by a lack in the in which the posterior fossa shows normal dimensions, the visualization of the septum pellucidum, by a widening of only finding can be an abnormal widening of the Magendie occipital horns and atria in a typical teardrop configuration, by foramen associated with a slight anticlockwise rotation of the an upward positioning of the III ventricle or a radial convergence vermis. The Blake’s pouch cyst is characterized by an expansion of the mesial cerebral sulci towards the III ventricle. In such of the IV ventricle in association with supratentorial cases fetal MRI allows a direct or indirect visualization of the hydrocephalus. Although the classic Dandy-Walker corpus callosum (Fig. 3)24 after 20 weeks of pregnancy in sagittal

Figs 4A and B: Dandy-Walker malformation at 29 weeks of pregnancy. Anticlockwise rotation of the cerebellar vermis and communication of the IV ventricle with a large liquoral retrocerebellar “cyst” with Figs 5A and B: Dandy-Walker malformation at 18 weeks of pregnancy. associated internal theca scalloping. Note the enlarged posterior fossa. The anticlockwise rotated vermis, appearing hypoplasic in its inferior Upward displacement of the torcular Herophili. (A) sagittal section, portion, and the cystic IV ventricle are easily visualized. (A) sagittal (B) coronal section section, (B) coronal section

63 M Lituania et al malformation can be easily diagnosed by ultrasound, sometimes depending on the time elapsed from the injury and on the the differential diagnosis between a less severe variant of the affected anatomical structure. malformation and a mega cysterna magna or an arachnoid cyst may arise from several familiar, infective, toxic (conditions in which the agenesis/hypogenesis of the cerebellar and metabolic causes. It can be primitive or associated with vermis is not described) can be very difficult, especially in other malformations, such as and presence of an advanced cranial ossification of the fetus that . In cases of primitive microcephaly presenting hinder a correct ultrasonographic assessment of the posterior with simplified gyration pattern (microlissencephaly), the lesions fossa. In such cases MRI is very important because it can seem to be caused by a defect in the neuronal proliferation of accurately describe the morphology and position of the the germinative matrix or by an excessive cellular death program, cerebellar vermis and the relationship between the posterior with a subsequent reduction of glioneuronal units and reduction fossa cyst and the IV ventricle. of the amount of white matter (Fig. 6). These are cases in which Once the presence of a Dandy-Walker complex malformation MRI plays a determinant role not only for the detection of is verified, MRI is necessary for accurately searching the signs microcephaly but above all for the analysis of cortical gyration, of the most frequently associated malformations (agenesis of that is simplified when only the primary sulci are visible, and the corpus callosum, , neurons heterotopia, they have a widened and flattened unusual appearance. The occipital cephalocele). This is very important for the prognosis, secondary sulci, usually already visible at gestation week 24, because a strict relation between associated malformations and are absent. The most appropriate time for the execution of MRI psychomotor development delays has been demonstrated. should be gestation week 30-34, which is not too early for the secondary sulci not to have appeared yet, nor too late, when Abnormal proliferation and migration of neurons and cortical the liquoral spaces appear reduced in thickness. Both in the organization anomalies. The diagnostic potential of MRI in cases of macrocrania and of macrencephaly or 25 this field is very high compared to ultrasound. The etiologic (increase of the cerebral volume), MRI allows an accurate spectrum of such pathologies is extremely broad: genetic, assessment of the relations among the theca, the cranial base infectious, metabolic, toxic, ischemic, traumatic. The resulting and the cerebral structures, because it is able to accurately lesions, independently form the underlying cause, are similar in visualize the pericerebral liquoral spaces. Besides it allows to all cases and they substantially differ from one another identify other possibly associated abnormalities, especially hydrocephalus.

Figs 6A to F: Microlissencephaly associated with midline malformation (Dandy-Walker) at 28 weeks of pregnancy. Fetal MRI shows a very small agyric brain, enlargment of the subarachnoid space, with a thin cortex in a micrencephalic fetus. Moreover, other associated anomalies are detected: Dandy-Walker malformation, hypoplastic and brainstem: (A, B) sagittal sections; (C, D) coronal sections; (E, F) axial sections

64 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

In the cases of , a condition in which a lissencephaly the cortex has an aberrant appearance, lacking or part of it grows in excess, possibly the normal lamination. In the Walker-Warburg syndrome, in associated with areas of , lissencephaly, which dilatation of ventricles, posterior fossa anomalies (similar polymicrogyria, heterotopia and gliosis, MRI can accurately to Dandy-Walker), ocular abnormalities and cephalocele are detect anatomical asymmetries because it allows to also observed, MRI allows an accurate assessment of the simultaneously visualize both hemispheres and to acquire posterior fossa structures. biometric measures, whatever the position of the fetus is. Fetal MRI imaging is also superior to ultrasound in The term complete lissencephaly or agyria (type I identifying schizencephaly, polymicrogyria27 and grey matter lissencephaly) refers to a complete absence of sulci; pachygyria, heterotopia . Subependymal heterotopia is characterized by or incomplete lissencephaly, is characterized by shallow and nodules that are isointense to the germinal matrix and located smooth sulci and thickening of the cortex.26 Type I along the ventricular walls. They cannot be reliably lissencephaly, observed in patients with of genes DCX distinguished from subependymal nodules seen in tuberous and LIS1, at histology shows a four layered cortex, in which the sclerosis; therefore, it is important to search for other signs of most internal and thick layer is made of neurons that have tuberous sclerosis, such as cortical hamartomas (which are interrupted their physiological migration process between hypointense compared to normal unmyelinated white matter on gestation week 12 and 16. A deletion of the gene LIS1 has been SSFSE images) and cardiac rhabdomyomas. Schizencephaly observed in all patients with Miller-Dieker syndrome, appears as a grey matter-lined cleft extending from the ventricles characterized by lissencephaly and facial anomalies. MRI to the subarachnoid space. Polymicrogyria appears as a localized accurately highlights the typical “8” configuration of the brain or generalized absence of the normal sulcation with multiple due to an absent opercularization of the Sylvian fissures and to abnormal infoldings of the affected cortex. an abnormally thick internal cortical layer (Fig. 7). In holoprosencephaly MRI can be useful to recognize the The most common form of lissencephaly is type II lobar forms, especially when the fusion of the frontal lobes is lissencephaly (cobblestone lissencephaly). It has been so slight that it cannot be detected by ultrasound. In such observed in several syndromes (Walker-Warburg syndrome, cases MRI is indicated on the basis of extracerebral findings congenital Fukuyama muscular dystrophy, cerebro-oculo- such as hypotelorism, microcephaly, labio-palatal schisis. Fetal muscular syndrome) deriving from deficits of proteins involved MRI allows a detailed prenatal evaluation of the upper lip and in muscular contraction and in CNS development. In the palate for the diagnosis of cleft lip and cleft palate.28 The Fukuyama syndrome, the deficit of merosin affects the migration identification of a secondary palate is particularly important of oligodendrocytes precursors, with a resulting altered because it is not often adequately seen by ultrasound. The myelination process, associated with alteration of the final knowledge of the appearance of isolated cleft secondary palate migration stage and of cortical organization. In this type of may enable prospective diagnosis of this anomaly by MRI.

Figs 7A to C: Miller-Dieker syndrome (confirmed by DNA analysis) at 34 weeks of pregnancy. Lissencephaly with verticalization of the Sylvian cisterns and slight ventriculomegaly associated with hypomyelination. (A) axial section, (B) coronal section, (C) posterior coronal section

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Although the sensitivity and specificity of MRI in the detection MRI allows better evaluation of the brain structure and the of cleft lip and palate and cleft secondary palate have not been skull defect, providing additional information for prenatal determined yet, we can easily predict a very useful application counseling, delivery planning and planning for postnatal of fetal MRI in the analysis and vigilance of fetal facial anomalies intervention30 (Figs 8-10). due to a combination of the improving visualization of several Spinal malformations. One of the major indications for fetal bony structures and of facial soft-tissue.29 MRI is the study of spinal osseous abnormalities detected by ultrasound. MRI can contribute to point out and analyze rare Fetal Cephalocele anomalies of the spinal cord, such as and segmentary dysgenesis, that are not always detected by Cephaloceles are defined as a herniation of intracranial contents ultrasound. Nevertheless, the most common spinal anomaly through a bony defect in the skull. Herniation of the meninges seen on ultrasound is myelomeningocele. Myelomeningocele alone is termed meningocele and if there is brain tissue present is always associated with Chiari II malformation and MRI is as well, . able to demonstrate the reduced dimensions of the posterior An encephalocele may simply result from a cranial defect, fossa, the downward displacement of the sinuses confluence or it may occur concurrently along with other more complex and of the trunco-cerebellar structures, the degree of vermis brain anomalies. herniation in the foramen magnum (directly dependant on the The contents of an encephalocele often undergo significant severity of the malformation) and the frequently associated rotation and distortion. The so-called “Chiari III malformation” CNS malformations (anomalies of the corpus callosum, cortical specifies a cerebellar herniation through a cervico-occipital dysplasias). defect. Brain injury. It represents one of the most common indication The exquisite contrast resolution of MRI should allow easy for fetal MRI.31,32 Regarding brain injury it is necessary to state differentiation between a CSF filled herniation and one filled in advance that harmful events occurring very early can interfere with brain parenchyma, especially at the skull base. with the normal development of the nervous structures, and may result in real malformative conditions. MRI, due to its anatomical accuracy and its capability of tissue differentiation, plays an important role in the diagnosis of this type of lesions (Figs 2, 11 and 12) . The destruction of fetal brain can be caused by several conditions: hypoxia, congenital infections (especially toxoplasmosis and cytomegalovirus), vascular and cardiac malformations, pregnancies with high risk for fetal brain damage (toxic and coagulative risk factors, maternal hypoxia, mechanic factors), hereditary metabolic defects (especially mitochondrial pathologies), tumors (Figs 13-17). In hemorrhagic lesions MRI, allowing to simultaneously Figs 8A and B: Atretic cephalocele at 33 weeks of pregnancy. (A) A visualize the whole brain and liquoral spaces, is more helpful, small extracranial mass containing a semifluid, desomogeneous tissue compared to ultrasound, in the detection of intraventricular (arrow) is seen at the posterior parietal lobe in a median location. (B) bleedings and especially, thanks to the high contrast resolution, Neonatal MRI: nearby the cephalocele a venous vestigial collector (arrow) draining into the superior sagittal sinus is seen

Figs 10A and B: Parieto-occipital cephalocele at 20 weeks of Figs 9A and B: Meningocele at 23 weeks of pregnancy. A sac with a pregnancy. The cerebral tissue and meninges protrude extracranially liquoral content is seen at a median parieto-occipital level. (A) sagittal through an evident opening of the theca. (A) sagittal section, (B) axial section, (B) axial section section

66 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

Figs 13A and B: Hemorrhagic cyst of the choroid plexus (arrow) at 30 weeks of pregnancy. (A) sagittal section, (B) coronal section

Figs 11A to D: Complicated malformation of the midline associated with a clastic lesion involving the cerebral hemispheres at 22 weeks of pregnancy. It might be referred to corpus callosum agenesis associated with a large telencephalic pseudocyst, that has progressively expanded determining a maturation arrest of the rostro-mesial portion of the Figs 14A and B: Hemorrhage of the choroids plexus at 36 weeks of cerebral hemispheres: (A, B) sagittal sections; (C, D) axial sections pregnancy. The bleeding is extended to the adjacent parenchyma with associated hydrocephalus. (A) fetal MRI coronal section. (B) the neonatal ultrasonographic examination shows a large hypoechoic area representing the resulting involutive-malacic lesion

Figs 15A and B: Cerebral hemorrhage at 30 weeks of pregnancy. A nucleo-capsular lesion, of desomogenous signal, mostly hypointense, is seen associated with dilatation of the adjacent ventricular spaces. (A) axial section, (B) coronal section

of juxtaventricular and intraparenchimal hemorrhages, even the small ones. T2* sequences allow to identify occult bleedings caused by underlying vascular malformations and capillary Fig. 12: Same case of the Figure 11: autopsy findings telangiectasias. Indirect signs of cerebral edema caused by

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Figs 16A to C: Results of fetal trauma at 26 weeks of pregnancy. Marked tissue loss with destructive characteristic on the cerebral surface with centrencephalic area of pseudoporencephaly and ventricular dilatation (A, B, C) axial sections

ischemia are seen on MRI as a reduction of the pericerebral spaces and ventricles and, although more rarely, as a reduced visualization of the cortical-subcortical junction. Direct signs of acute ischemic lesion should be seen as focal changes of the white matter signal but, due to the physiological high water content of unmyelinated brain, the differentiation between normal white matter and ischemic lesions can be very difficult or even impossible. On the other hand focal ischemic lesions are easily identified when they show a cavitated configuration as they appear more hyperintense in T2 than edema and gliosis. Figs 17A to C: Posterior fossa hemorrhage at 22 weeks of pregnancy. Cerebral tumors and arachnoid cysts: the contribute of MRI in Large hemorrhage involving the pericerebellar liquoral spaces with these cases is limited, apart from the possibility of a more accurate associated hemorrhagic extension into the lateral ventricles. (A) sagittal section, (B, C) coronal sections localization of the tumoral or cystic lesion and of its relation with the adjacent anatomical structures (Figs 18 and 19).

Figs 18A to C: Intracranial teratoma at 27 weeks of pregnancy. Large midline expansive lesion, showing heterogenous signal for the presence of cystic, calcified and hemorrhagic components. Note the associated supratentorial marked ventriculomegaly. (A) sagittal section, (B) coronal section, (C) axial section

68 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

Figs 19A to C: Temporal arachnoid cyst at 30 weeks of pregnancy. Isoliquoral area determining mass effect on the right temporal pole and with controlateral extension and posterior dislocation of the brainstem. (A) Axial, (B) coronal section, (C) Neonatal CT scan Vascular malformations: the most common are the aneurysm Chest Anomalies of the vein of Galen (Vein of Galen aneurysmal malformation – Lesions of considerable dimensions such as lymphangiomas VGAM),16 dural sinus malformation (DSM) (Fig. 20), and pial are commonly deforming the neck and extending to the arteriovenous fistulas. mediastinum, while lesions occupying the anterolateral region The role of MRI, besides that of a possible use of of the neck that are often represented by theratomas may cause angiographic sequences, mainly consists in the assessment of compression and dislocation, with severe obstruction of the the cerebral parenchyma and in the identification of associated airways.33 The fetal airways are seen as high signal intensity ischemic and hemorrhagic lesions, that can be related to a areas due to the presence of fluid in the tracheobronchial tree. negative prognosis. Ischemic and hemorrhagic lesions show The normal fetal lung on T2-weighted images is different characteristics depending on when they occurred, and homogeneous, and has moderate signal intensity. With fetal may appear with different patterns such as periventricular lung maturation, increased alveolar fluid production results in leukomalacia, focal atrophy, cortical necrosis, stenogyria. higher signal intensity. Low signal intensity of lungs may be suggestive of pulmonary hypoplasia; MRI can also accurately determine the volume of the lungs.34-36 Fetal pulmonary hypoplasia occurs as result of several disorders, including bilateral renal agenesis, congenital diaphragmatic hernia (CDH), pleural effusions, thoracic masses, skeletal dysplasia and preterm premature rupture of the membranes. Magnetic resonance spectroscopy of fetal lungs has also been attempted.37 The rationale is to noninvasively assess the relative concentrations of phosphatidylcoline (lecithin) and other phospholipidic components of the surfactant. There are several technical limitations left that need to be overcome before magnetic resonance spectroscopy becomes routinely available for this purpose. Once such problems are solved, this may get round the need for amniocentesis to assess the maturity of lungs. The main thoracic anomalies for which MRI is performed are CDH (Figs 21 and 22) congenital cystic adenomatoid malformations38 (Figs 23 and 24) and bronchopulmonary sequestration, bronchogenic cyst (Fig. 25) and tracheolaringeal Fig. 20: Sinuses confluence dilatation (arrowheads) and thrombosis atresia.39 at 22 weeks of pregnancy. An oval shaped, hypointense lesion referable to a blood clot (arrow) can be seen within an abnormally dilated torcular Congenital diaphragmatic herniations, with an incidence of Herophili 1/2400-3000 live births, includes a group of diaphragmatic defects 69 M Lituania et al

Figs 21A to C: Diaphragmatic hernia at 27 weeks of pregnancy. The left hemithorax appears almost completely occupied by the abdominal viscera, herniated through a mid-posterior diaphragmatic defect. (A,B) sagittal sections (C) coronal section Figs 24A and B: Hybrid form of congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) with subdiaphragmatic involvement at 22 weeks of pregnancy. Area of hyperexpansion of the right inferior lobe with tendency to transdiaphragmatic extension (arrow). (A) sagittal section (B) coronal section

Figs 25A to C: Bronchogenic cyst at 27 weeks of pregnancy. Large fluid-filled lesion of the right lung at the confluence of the lobes. (A) coronal section, (B) sagittal section, (C) axial section Figs 22A and B: Eventration of the diaphragm at 27 weeks of pregnancy. On the left side the diaphragm and the underlying abdominal viscera appear elevated in a dome-shaped configuration. (A) coronal section, (B) paramedian sagittal section when the stomach lies in its normal position. It can be accurately diagnosed by MRI before birth in almost 60% of cases.40 This has two major advantages: the exclusion of commonly associated defects and the possibility to plan the delivery in appropriate facilities for neonatal intensive care and for surgical repair of the defect. Despite recent advances in postnatal care, the mortality rate of patients with congenital diaphragmatic hernia remains high: most of these patients die from respiratory failure due to pulmonary hypoplasia. In the cases of isolated congenital diaphragmatic herniation the lung-to-head-ratio (LHR) is probably the most efficient Figs 23A to C: Cystic adenomatoid malformation (macrocystic type) sonographic predictor of outcome. MRI could also be useful as at 26 weeks of a twin pregnancy. The inferior lobe of the right lung is an additional tool for the quantitative and qualitative evaluation mainly involved, the lesion showing a bunch-shaped configuration. of the fetal lungs,41 with FLV measurements.42,43 Good agreement (A) sagittal section (B) coronal section (C) axial section between lung volumes measured by MRI and those measured by 3D ultrasonography is demonstrated. in which some portions of the abdominal content protrude into Traditionally, MRI produces static images and is inferior to the chest cavity, through a posterolateral defect in 95% of cases. ultrasound in assessing cardiac anomalies. Newer MRI MRI enables the recognition of small parts of herniated liver. techniques include rapid hybrid sequences able to produce The diaphragmatic defect can be difficult to detect by ultrasound cine images of the cardiac motion.

70 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

Gastrointestinal Anomalies MRI appears to be accurate for establishing or ruling out a prenatal diagnosis of esophageal atresia, and should be Fetal gastrointestinal tract disorders are usually diagnosed by considered in fetuses who are at high risk based on ultrasound ultrasound. Small bowel dilatation, polihydramnios and findings.38,44,47 hyperechoic intestine are the most common findings that may Esophageal and gastric duplication can be detected by MRI identify a gastrointestinal malformation. However, many of these (Figs 26 and 27). The stomach and gallbladder are readily findings are not specific, may occur late in pregnancy, and may identified due to a bright signal on T2W images. The colonic be related to transient normal variants or functional obstruction. haustral pattern is visible after 25 weeks. The main cause of MRI provides a complete visualization of the fetal GI tract proximal bowel obstruction are duodenal (Fig. 28) and jejunal showing its specific signals44 and may locate the level of bowel atresia; the causes of distal bowel obstruction include ileal obstruction,45,46 and detect a microcolon. It is helpful in atresia, meconium ileus and small left colon syndrome. Intestinal identifying intra-abdominal hemorrhage. atresia presents on MRI with three signs: proximal intestinal dilatation, abnormal signal of the content and microcolon. MRI shows a very thin rectum, of much reduced diameter and with abnormal signal. Abdominal wall defects are usually detected by ultrasound, but MRI is useful in case of gastroschisis to diagnose the associated intra-abdominal bowel obstruction48 (Fig. 29).

Figs 26A and B: Esophageal duplication and double renal collecting system on the left side at 33 weeks of pregnancy. A liquid mass without an apparent communication with the esophageal lumen (arrow) is seen at the mediastinum in a median paraesophageal location posterior to the tracheal bifurcation. On the left side a non dilated Figs 27A and B: Non communicating gastric duplication at 28 weeks double renal collecting system is visualized. (A) coronal section, of pregnancy. A small cystic round lesion (arrow) is seen adjacent to (B) paramedian sagittal section the gastric fundus (A, B) coronal sections

Figs 28A to C: Duodenal atresia at 30 weeks of pregnancy. Marked dilatation of the stomach and of part of the duodenum in association with esophageal dilatation (arrows) due to reflux (A, B, C) coronal sections

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Figs 29A and B: Gastroschisis with associated signs of bowel obstruction at 30 weeks of pregnancy. (A) Marked dilatation of the intestinal lumen due to malrotation. (B) Through the paraumbilical defect free loops of bowel (arrow) can be seen in the amniotic fluid Figs 32A and B: Adrenal cyst at 32 weeks of pregnancy. The rounded cystic lesion involving the left adrenal space was identified as a cystic neuroblastoma at histology. (A) sagittal section (B) coronal section

Genitourinary Anomalies The application of MRI in urinary pathology3,49,50 is based on the high signal intensity of the urine within the excretory system and on the possibility of always visualizing the urinary bladder, which constitutes a very good reference point. Figs 30A to C: Intrahepatic lymphangioma at 27 weeks of gestation. Anomalies of the genitourinary system are common. Multiseptated lesion of the right hepatic lobe. (A) coronal section, (B) Sonography is an excellent tool for the assessment of the fetal sagittal section, (C) axial section genitourinary tract. However, some factors, including the patient’s body habitus and oligohydramnios, often prevent an optimal assessment of anomalies of the genitourinary system using sonography. MRI is extremely useful in evaluating suspected anomalies and it is especially valuable for the imaging of fetuses with abnormalities of the genitourinary system that have resulted in oligohydramnios and in whom lethal pulmonary hypoplasia is suspected. Fetal MR urography performed using T2W sequences, especially in coronal sections, can show both the ureters and their size, and the ectopic position of kidneys. MRI can accurately identify the different forms of renal cystic disease, especially when the diagnosis is not confirmed on ultrasound. Multicystic dysplastic kidneys appear as enlarged Figs 31A and B: Hemangioendothelioma at 30 weeks of pregnancy. kidneys with randomly scattered cysts of different size (Fig. Marked hepatomegaly. The liver presents a lobulated, disomogeneous 34). Prenatal diagnosis of autosomal recessive polycystic kidney appearance with abnormal high signal areas at the right lobe. (A) sagittal section, (B) axial section disease is usually performed by sonography. Prenatal diagnosis of fetal renal masses can be performed by ultrasound and MRI (Fig. 35). Liver masses can be detected by MRI (Figs 30 and 31). The diagnosis of cloachal malformations is difficult by The retroperitoneal space and the surrounding soft tissues means of ultrasound; MRI may demonstrate a moderately dilated can be well visualized by MRI and retroperitoneal masses can rectum with an abnormal fluid signal. The rectum appears to be be evidenced (Figs 32 and 33). normally located under the bladder neck, but it is separated

72 The Role of Magnetic Resonance Imaging in the Diagnosis of Fetal Malformations

Figs 33A to C: Cystic lymphangioma at 32 weeks of pregnancy. Hyperintense, irregularly outlined lesion extending in the right retroperitoneal region with invasion of the ipsilateral subcutaneous soft-tissues (arrows). (A, B) coronal sections (C) sagittal section

Figs 34A to C: Multicystic dysplastic kidney disease (right side) at 30 weeks of pregnancy. (A) coronal section (B) sagittal section (C) axial section. The controlateral normal kidney can be recognized in this axial view (arrow) Fig. 35: Mesoblastic tumor of the kidney at 34 weeks of pregnancy – coronal section. Increase of the right kidney volume, due to a from the bladder by a low signal structure corresponding to a homogeneous polilobated mass at the inferior pole (arrow) dilated genitourinary tract.

Sacrococcygeal Teratoma It is now generally accepted that these tumors originate Although rare, is the most common from totipotent cells from Hansen’s node or primitive germ cells tumor of the fetus and neonate, with a reported incidence of 1/ during their migration from the yolk sac to the genital ridge and 35,000-40,000 live births. escape the normal inductive influences. It has been considered either a neoplasm composed of The natural history of prenatal diagnosed sacrococcygeal tissues arising from all three germ layers or a neoplasm composed teratomas differs from that of the postnatally diagnosed ones. of a wide variety of tissues foreign to the anatomic site in which Malignant degeneration, the primary cause of death in postnatal they arise. sacrococcigeal teratoma, is rare in utero. Prenatal assessment

73 M Lituania et al of the fetus is critical for counseling and prenatal/postnatal and to study placental anomalies. Besides, some cerebral lesions management. caused by metabolic diseases or by a decreased oxygen supply Also, with the development of in utero treatment for could be detected by protonic MRI spectroscopy on the basis sacrococcygeal teratoma it is important to select appropriate of the altered cerebral tissue metabolism. candidates for fetal surgery. Thanks to spectroscopy and MR angiography some crucial Because of the acoustic shadowing due to the fetal pelvic points of the fetomaternal unit (such as apparently isolated bones, sonography cannot always define the most cephalic ventriculomegalies detected on ultrasound, high risk of fetal extent of sacrococcygeal teratomas. MRI is superior to anomalies in mothers with an already affected fetus or child, sonography in assessing the intrapelvic and/or intraspinal extent reduced intrauterine growths, the course and monitoring of of the tumor and in evaluating the possible compression effects hydrocephalus and posterior fossa anomalies associated with on the pelvic organs by the tumor.51 MRI is also able to assess myelomeningocele in the Chiari II syndrome) will be better the content of sacrococcygeal teratoma.52 Both on ultrasound managed. and on MRI it may appear cystic, solid or mixed and it may contain typical patterns secondary to areas of tumor necrosis, REFERENCES cystic degeneration, internal hemorrhage and calcification. The 1. Casele H, Meyer J. The selective use of magnetic resonance prognosis of prenatally detected sacrococcygeal teratomas imaging in prenatal diagnosis. Ultrasound Obstet Gynecol seems to be related non only to the size of the mass but also to 2004;23(2):105-10. its content. Fetuses with predominantly solid and highly 2. Huisman TA, Kellenberger CJ. MR imaging characteristics of vascularized masses have a poorer prognosis than fetuses with the normal fetal gastrointestinal tract and abdomen. Eur J Radiol tumors that are mainly cystic and avascular. The presence of 2007. hemorrhage in the tumor can be detected by MRI with T1W or 3. Laifer-Narin S, Budorick NE, Simpson LL, et al. Fetal magnetic echo-planar sequences, and an evaluation of the possible fetal resonance imaging: a review. Curr Opin Obstet Gynecol anemia should be promptly made. MRI is also an extremely 2007;19(2):151-6. valuable tool in the assessment of the compression or 4. Saguintaah M, Couture A, Veyrac C, et al. MRI of the fetal involvement of the adjacent organs, conditions that favor the gastrointestinal tract. Pediatr Radiol 2002;32(6):395-404. 5. Sandrasegaran K, Lall C, Aisen AA, et al. Fast fetal magnetic morbidity of sacrococcygeal teratoma. 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