Assessment of fetal brain abnormalities

52 Assessment of fetal brain abnormalities Ritsuko K. Pooh introduction Recent advanced ultrasound imaging technologies such as high-frequency transvaginal scanning and three-dimensional (3D) sonography have been remarkably improved, and introduction of those technologies in clinical practice has contributed to prenatal evaluation of fetal central nervous system (CNS) development and assessment of CNS abnormalities in utero. Sonographic assessment of the fetal brain in the sagittal and coronal sections requires an approach through anterior/ posterior fontanelle and/or the sagittal suture. Transvaginal sonography of the fetal brain opened a new field in medicine, “neurosonography” (1). Transvaginal approach to the normal fetal brain during the second and third trimesters was introduced in the beginning of 1990s. It was the first practical application of 3D CNS assessment by two-dimensional (2D) ultrasound (2). Transvaginal observation of the fetal brain offers sagittal and coronal views of the brain (3–6) through the fontanelles and/or the sagittal suture as ultrasound windows. Serial oblique sections (1) via the same ultrasound window reveal the intracranial morphology in detail. This method has contributed to the prenatal assessment of congenital CNS anomalies and acquired brain damage in utero. Furthermore, the brain circulation demonstrated by transvaginal power Doppler was first reported in 1996 (7,8); brain vascularity and blood supply have become clearly detectable afterward. Three-dimensional ultrasound is one of the most attractive modality in a field of fetal ultrasound imaging. Automatic scan by dedicated 3D transducer produces motor-driven automatic sweeping and is called as a fan scan. With this method, a shift and/or angle change of the transducer is not required during scanning and scan duration needs only several seconds. After the acquisition of the target organ, multiplanar imaging analysis and tomographic imaging analysis are possible. Combination of both transvaginal sonography and 3D ultrasound (9–19) has been a great diagnostic tool for evaluation of 3D structure of fetal CNS. Recent advanced 3D ultrasound equipments have several useful functions as follows: l l l l l l l Surface anatomy imaging Bony structural imaging of the calvaria and vertebrae (13,14) Multiplanar imaging of the intracranial structure Tomographic ultrasound imaging of fetal brain in the any cutting section (Fig. 1) Thick slice imaging of the intracranial structure Simultaneous volume contrast imaging of the same section or vertical section of fetal brain structure Volume calculation of target organs such as intracranial cavity, ventricle, choroid plexus, and intracranial lesions (20–25) l Three-dimensional sono-angiography of the brain circulation (3D power Doppler) (8) Fetal neuroimaging with advanced 3D technology is an easy, noninvasive, and reproducible method. It produces not only comprehensible images but also objective imaging data. Easy storage/extraction of raw volume data set enables easy off-line analysis and consultation to neurologists and neurosurgeons. ventriculomegaly and hydrocephalus “Hydrocephalus” and “ventriculomegaly” are both the terms used to describe dilatation of the lateral ventricles. However, those two should be distinguished from each other. Hydrocephalus signifies dilated lateral ventricles resulted from increased amount of cerebrospinal fluid (CSF) inside the ventricles and increased intracranial pressure, while ventriculomegaly is the dilatation of lateral ventricles without increased intracranial pressure, due to cerebral hypoplasia or CNS anomaly such as agenesis of the corpus callosum (26,27). Of course, ventriculomegaly can sometimes change into hydrocephalic state. In sonographic imaging, those two intracranial conditions can be differentiated by visualization of subarachnoid space and appearance of choroid plexus. In normal condition, subarachnoid space, visualized around both the cerebral hemispheres, is well preserved during pregnancy. Choroid plexus is a soft tissue and is easily affected by intracranial pressure. Obliterated subarachnoid space and dangling choroid plexus are observed in the case of hydrocephalus. By contrast, the subarachnoid space and choroid plexus are well preserved in cases of ventriculomegaly. It is difficult to evaluate subarachnoid space in the axial plane because the subarachnoid space is observed in the parietal side of the hemispheres. It is suggested that the evaluation of enlarged ventricles should be done in the parasagittal and coronal views by transvaginal approach to the fetal brain or 3D multidimensional analysis (Fig. 2). As a screening examination, the measurement of atrial width (AW) is useful with a cutoff value of 10mm (28,29). In normal fetuses, blood flow waveforms of dural sinuses, such as the superior sagittal sinus, vein of Galen, and straight sinus have pulsatile pattern (30). However, in cases with progressive hydrocephalus, normal pulsation disappears and blood flow waveforms become flat pattern (30). Intracranial venous blood flow may be related to increased intracranial pressure. Variety of Mild Ventriculomegaly with AW 10–15mm Mild ventriculomegaly is defined as of a width of the atrium of the lateral cerebral ventricles of 10 to 15mm. It has been reported that mild ventriculomegaly with AW 10 to 15mm resolves in 29%, remains stable in 57%, and progresses in 14% of the cases during pregnancy (31). In cases of 52.1 52.2 CLINICAL MATERNAL–FETAL MEDICINE ONLINE Exp 5.7cm / 1.6 /28Hz 0000521 GA=20w2d –4–3 –3 TIs 0.1 10993-06-02-20-26 –4 –3 2010/10/04 9:01:37 PM –2 Default Qual high2 B90°/V100° 3D Static 0.0/9.3cm/19Hz 4 –3 2005/06/27 05:40:36 PM TIs 0.1 –2 Surface Qual max B124°/V90° SRI II 5 3D Static 3.0 mm –1 2 3 1 –1 4 2 1 3 4 Figure 1 Tomographic ultrasound imaging by three-dimensional transvaginal sonography. Normal brain at 20 weeks (left) and 31 weeks (right) on the coronal cutting sections. Note the changing cortical development between those two different gestational stages. –4–3 4 –3 –2 –4–3 Surface Qual max B147°/V 120 SRI II 3D static –3 –2 Default Qual max B118°/V 120 3D static 4.0 5.0 –1 2 4 5 1 –1 4 2 1 3 4 Figure 2 Hydrocephalus (left) and ventriculomegaly (right). Tomographic ultrasound imaging of X-linked hydrocephalus at 21 weeks (left) and ventriculomegaly at 25 weeks (right). Note the obliterated subarachnoid space in the hydrocephalic case compared with normal subarachnoid space in the ventriculomegaly case. ventriculomegaly with AW of 10 to 13mm at referral, the ultimate fetal outcome and prognosis depends on associated abnormalities. Generally, in cases of mild fetal ventriculomegaly with a normal karyotype and an absence of malformations, the outcome appears to be favorable (32). Pilu and his colleagues (33) reviewed 234 cases of borderline ventriculomegaly including an abnormal outcome in 22.8% and concluded that borderline ventriculomegaly carries an increased risk of cerebral maldevelopment, delayed neurologic development, and, possibly, chromosomal aberrations. Isolated mild ventriculomegaly with AW of 10 to 12mm may be normal variation. Signorelli and colleagues (34) described that their data of normal neurodevelopment between 18 months and 10 years after birth in cases of isolated mild ventriculomegaly (AW of 10–12mm) should provide a basis for reassuring counseling. Ouahba and colleagues (35) recently reported the outcome of 167 cases of isolated mild ventriculomegaly and concluded that in addition to associated anomalies, three criteria are often associated with an unfavorable outcome: AW greater than 12mm, progression of the enlargement, and asymmetrical and bilateral ventriculomegaly. Moderate to Severe Ventriculomegaly and Hydrocephalus with AW>15mm The term of “hydrocephalus” does not identify a specified disease, but is a generic term that means a group of pathologic conditions due to abnormal circulation of CSF. Treatment method of hydrocephalus should be selected according to age of onset and symptoms. Congenital hydrocephalus is classified into three categories by causes that disturb CSF circulation pathway: simple hydrocephalus, dysgenetic hydrocephalus, and secondary hydrocephalus (15,26). 1. Simple hydrocephalus Simple hydrocephalus, caused by developmental abnormality that is localized within CSF circulation pathway, includes aqueductal stenosis, atresia of foramen Monro, and maldevelopment of arachnoid granulation. 2. Dysgenetic hydrocephalus Dysgenetic hydrocephalus indicates hydrocephalus as a result of cerebral developmental disorder in early developmental stage and includes hydranencephaly, holoprosencephaly, porencephaly, schizencephaly, Dandy–Walker malformation, dysraphism, and Chiari malformation. 52.3 ASSESSMENT OF FETAL BRAIN ABNORMALITIES –1 2 1 3 4 Figure 3 Encephalocele. Tomographic ultrasound imaging (upper) and MR imaging (lower) in a case of encephalocele at 28 weeks of gestation. 3. Secondary hydrocephalus Secondary hydrocephalus is a generic term indicating hydrocephalus caused by intracranial pathologic condition, such as brain tumor, intracranial infection, and intracranial hemorrhage. In cases with progressive hydrocephalus, there may be seven stages of progression: (i) increased fluid collection of lateral ventricles, (ii) increased intracranial pressure, (iii) dangling choroid plexus, (iv) disappearance of subarachnoid space, (v) excessive extension of the dura and superior sagittal sinus, (vi) disappearance of venous pulsation, and finally (vii) enlarged skull (24). In general, both hydrocephalus and ventriculomegaly are still evaluated by the measurement of biparietal diameter and AW in transabdominal axial section. Although all cases have similar ventricular appearance, the causes of ventriculomegaly vary, such as Chiari type II malformation, aqueductal obstruction, and amniotic band syndrome (ABS). In the case of ABS, amniotic band attached to the scalp resulted in partial cranial bone defect and a small cephalocele, which may have caused Monro obstruction and enlarged ventricles. From our data of 23 ventriculomegaly cases with AW>15 mm (27), 9 cases (39.1%) had no other CNS abnormality, but 2 out of those 9 were complicated with chromosomal aberration. Four cases out of seven without any complication had favorable postnatal prognosis after ventricular–peritoneal shunting procedure. Among the rest of 14 cases with other CNS abnormalities, holoprosencephaly was detected in 5 cases and myelomeningocele in 5 cases (27). neural tube defects Cranium Bifidum Cranium bifidum is classified into four types of encephaloschisis (including anencephaly and exencephaly), meningocele, encephalomeningocele, encephalocystocele, and cranium bifidum occultum. Encephalocele occurs in the occipital region in 70% to 80%. Acrania, exencephaly, and anencephaly are not independent anomalies. It is considered that dysraphia (absent cranial vault, acrania) occurs in very early stage and disintegration of the exposed brain (exencephaly) during the fetal period results in anencephaly. Encephalocele (Fig. 3) is often observed in the median section and in the parietooccipital part. ABS should be differentiated from acrania during early pregnancy, because ABS has completely different pathogenesis from acrania/exencephaly. In cases of ABS, cranial destruction occurs secondary to an amniotic band; similar appearance is often observed. Spina Bifida Spina bifida aperta, manifest form of spina bifida, is classified into four types: meningocele, myelomeningocele, myelocystocele, and myeloschisis. In myelomeningocele, the spinal cord and its protective covering (the meninges) protrude from an opening in the spine. In meningocele, the spinal cord develops normally but the meninges protrude from a spinal opening. The most common location of the malformations is the lumbar and sacral areas of the spinal cord. Chiari type II malformation and secondary hydrocephalus/ventriculomegaly are mostly, and scoliosis or kyphosis occasionally, associated with open spina bifida. Surface anatomy of the fetus and appearance of clubfoot, which occasionally manifests early in 52.4 CLINICAL MATERNAL–FETAL MEDICINE ONLINE 9830-04-08-17-21 GA=20w6d 0.5/ 8.8 Figure 4 Myelomeningocele. Two-dimensional (2D) ultrasound of myelomeningocele (upper left) and myelomeningocele with kyphosis (lower left), 3D ultrasound (middle), and MRI (right). Right upper MRI shows Chiari type II malformation (arrows). Clear visualization of spinal cord protrusion is obtained by 2D ultrasound and MRI. The 3D ultrasound images show the bony structure that helps to determine the level of spina bifida and lower extremity appearance. mid-gestation as a complication of spinal bifida, are easily demonstrable by using 3D ultrasound. The 3D ultrasound with maximum mode can demonstrate bony structure (Fig. 4) and is helpful to detect the spinal levels of lesion and to predict neurologic prognosis. Although most myelomeningoceles are demonstrated as a protruding swelling, fetal back appears flat in the type of myeloschisis; therefore, open spina bifida may be often overlooked. Because more than 80% of cases of open spina bifida are associated with ventriculomegaly due to Chiari type II malformation, demonstration of ventriculomegaly is usually the first observable sign leading to the detailed examination of spine and the subsequent diagnosis of spinal bifida. prosencephalic developmental disorder Holoprosencephaly Holoprosencephalies are classified into three varieties: alobar, semilobar, and lobar types. Facial abnormalities such as cyclopia, ethmocephaly, cebocephaly, flat nose, cleft lip, and palate are invariably associated with holoprosencephaly and extracerebral abnormalities. Facial abnormalities are often associated with holoprosencephaly. Agenesis of the Corpus Callosum Absence of the corpus callosum (AOCC) is divided into complete agenesis, partial agenesis, or hypogenesis. Chromosomal aberration or syndromic diseases may occasionally be related to agenesis of the corpus callosum. Colpocephalic ventriculomegaly with disproportionate enlargement of trigones, occipital horns and temporal horns, and superior elongation of the third ventricle is usually observed. Interhemispheric cyst is often associated with AOCC and some cases are with pericallosal lipoma. Complete AOCC is demonstrated in the coronal and sagittal sections by sonography and fetal MRI. Typical shape of enlarged ventricles associated with AOCC is colpocephaly with large occipital horns. Typical radiated formation of brain vessels in the sagittal section is demonstrated by color Doppler study. As the corpus callosum is depicted after 17 or 18 weeks of gestation by ultrasound, it is impossible to diagnose agenesis of the corpus callosum prior to this age (36). posterior fossa anomaly Chiari Malformation Chiari classified anomalies with cerebellar herniation in the spinal canal into three types by contents of herniated tissue: contents of type I is a lip of cerebellum; type II part of cerebellum, fourth ventricle and medulla oblongata, and pons; and type III large herniation of the posterior fossa. Thereafter, type IV with just cerebellar hypogenesis was added. However, this classification occasionally leads to confusion in neuroimaging diagnosis. Therefore, at present, the classification as below is advocated: type I not associated with myelomeningocele, type II (schematic picture is shown in Fig. 5 upper left) associated with myelomeningocele, type III associated with cephalocele or craniocervical meningocele, and type IV associated with marked cerebellar hypogenesis and posterior fossa shrinking. Chiari malformation occurs according to i) inferior displacement of the medulla and the fourth ventricle into the upper cervical canal, ii) elongation and thinning of the upper medulla and lower pons and persistence of the embryonic flexure of these structures, iii) inferior displacement of the lower cerebellum through the foramen magnum into the upper cervical region, and iv) a variety of bony defects of the foramen magnum, occiput, and upper cervical vertebra (37). Hydrocephalus is caused by 52.5 ASSESSMENT OF FETAL BRAIN ABNORMALITIES C Norm al IIIrd ventricular deformation C M P C Elongation of aqueduct M P M Elongation of IVth ventricle Medullary kink c Ritsuko K. Pooh, 2004 Herniation of cerebellar tonsil into vertebral column * * Figure 5 Chiari type II malformation. Schematic picture of Chiari type II malformation (upper left). Elongation and stenosis of the aqueduct and fourth ventricle in the specimen from aborted fetus at 21 weeks (upper middle) are shown. Lower brain images are lemon sign and banana sign from the left. Arrowheads indicate indentations of lemon-shaped skull and banana-shaped cerebellum. Lower middle picture shows the lemon sign on the autopsy of an aborted fetus. Right sagittal ultrasound images show normal cerebrospinal structure, Chiari type II malformation without kink, and Chiari II with medullary kink from above. obstruction of fourth ventricular outflow or associated aqueductal stenosis. Eighty-eight percent of fetuses with open spina bifida develop ventriculomegaly, by 21 weeks of gestation in the majority of cases (38). As prenatal neuroimaging of Chiari malformation, lemon and banana signs (39) are circumstantial evidences of Chiari malformation, which are easily demonstrated in the early second trimester. Lemon sign indicates deformity of the frontal bone, and banana sign indicates abnormal shape of cerebellum without cisterna magna space (Fig. 5, lower). Herniation of the cerebellar tonsil and medulla oblongata and medullary kink are demonstrable (Fig. 5, right). Small clivus–supraocciput angle is seen in cases of Chiari malformation (40). dandy walker malformation, dandy walker variant, megacisterna magna During development of the fourth ventricular roof, a delay or total failure of the foramen of Magendie to open occurs, allowing a buildup of CSF and development of the cystic dilation of the fourth ventricle. Despite the subsequent opening of the foramina of Luschka (usually patent in Dandy–Walker malformation), cystic dilatation of the fourth ventricle persists and CSF flow is impaired. At present, the term “Dandy–Walker complex” by Barkovich et al. (41) is used to indicate a spectrum of anomalies of the posterior fossa that are classified by axial CT scans as it follows. Dandy–Walker malformation, Dandy–Walker variant, and megacisterna magna seem to represent a continuum of developmental anomalies of the posterior fossa (41). Figure 6 (upper) shows the differential diagnosis of hypoechoic lesion of the posterior fossa, and typical sonographic images of Dandy–Walker malformation are shown in the lower part of Figure 6. l l l (Classic) Dandy–Walker malformation: cystic dilatation of fourth ventricle, enlarged posterior fossa, elevated tentorium, and complete or partial agenesis of the cerebellar vermis. Dandy–Walker variant: variable hypoplasia of the cerebellar vermis with or without enlargement of the posterior fossa. Megacisterna magna: enlarged cisterna magna with integrity of both cerebellar vermis and fourth ventricle. neuronal proliferation disorder Microcephaly Microcephaly is defined as a head circumference that is more than two standard deviations below the normal mean for age, sex, race, and gestation. Infections such as with rubella, cytomegalovirus, varicella (chicken pox) virus, and toxoplasmosis, radiation, medications, chromosome abnormalities, and genetic diseases may cause microcephaly. Occasionally, microcephaly occurs with late onset during pregnancy (42). neuronal migration disorders Neuronal migration disorders are caused by the abnormal migration of neurons in the developing brain and nervous system. Neurons must migrate from the areas where they are born to the areas where they will settle into their proper neural 52.6 CLINICAL MATERNAL–FETAL MEDICINE ONLINE Normal Cystic dilataion of IVth ventriclev Arachnoid cyst Megacisterna magna Infratentorial arachnoid cyst DW variant DW malformation Cerebellar dysplasia C * * Figure 6 Differential diagnosis of hypoechoic lesion of the posterior fossa (upper) and typical sonographic images of Dandy–Walker malformation (lower). Abbreviation: C, cerebellum. Asterisks indicate cystic dilatation of the fourth ventricle. circuits. Neuronal migration, which occurs as early as the second month of gestation, is controlled by a complex assortment of chemical guides and signals. When these signals are absent or incorrect, neurons do not end up where they belong. This can result in structurally abnormal or missing areas of the brain in the cerebral hemispheres, cerebellum, brainstem, or hippocampus, including schizencephaly, porencephaly, lissencephaly, agyria, macrogyria, pachygyria, microgyria, micropolygyria, neuronal heterotopias (including band heterotopia), agenesis of the corpus callosum, and agenesis of the cranial nerves. Symptoms vary according to the specific disorder and the degree of brain abnormality and subsequent neurologic losses, but often feature poor muscle tone and motor function, seizures, developmental delays, mental retardation, failure to grow and thrive, difficulties with feeding, swelling in the extremities, and a smaller than normal head. Most infants with a neuronal migration disorder appear normal, but some disorders have characteristic facial or skull features. Lissencephaly Lissencephaly is very rare and characterized by a lack of gyral development and divided into two types. Lissencephaly type I shows a smooth surface of the brain and cerebral wall is similar to that of an approximately 12-week-old fetus (43). Isolated lissencephaly (Fig. 7) or Miller– Dieker syndrome is associated with additional craniofacial abnormalities, cardiac anomalies, genital anomalies, sacral dimple, creases, and/or clinodactyly. Lissencephaly type II shows cobblestone appearance. Walker–Warburg syndrome with macrocephaly, congenital muscular dystrophy, cerebellar malformation, and retinal malformation or Fukuyama congenital muscular dystrophy with microcephaly and congenital muscular dystrophy has been proven. 52.7 ASSESSMENT OF FETAL BRAIN ABNORMALITIES 20 w 25 w 31 w Figure 7 Changing appearance of Sylvian fissure in the anterior coronal section (upper) and abnormal Sylvian fissure in cases of migration disorder (lower). At 20 weeks of gestation, bilateral Sylvian fissures (arrowheads) appear to be indentations (left). With cortical development, Sylvian fissures are formed during the latter half of second trimester (middle) and become as lateral sulci. Sylvian fissure appearance is one of the most reliable ultrasound markers for the assessment of cortical development. Lower MR images show coronal cutting sections of various migration disorders after 30 weeks of gestation: Isolated lissencephaly, cobblestone lissencephaly, and pachygyria from left. Recently, classification has been made based on associated malformations and etiologies. - Classic lissencephaly (previously known as type I lissencephaly) Lissencephaly due to LIS1 gene mutation Type I isolated lissencephaly Link to chromosome 17p13.3 and chromosome Xq24-q24 Miller–Dieker syndrome link to chromosome 17p13.3 Lissencephaly due to doublecortin gene mutation Lissencephaly type I, isolated, without other genetic defects - Lissencephaly X-linked with AOCC (ARX gene) - Lissencephaly with cerebellar hypoplasia Norman–Roberts syndrome (mutation of reelin gene) - Microlissencephaly (lissencephaly and microcephaly) - Cobblestone lissencephaly (previously known as type II lissencephaly) Walker–Warburg syndrome, HARD(E) syndrome Fukuyama syndrome linked to chromosome 9q31, fukutin (44) Muscle–eye–brain disease A few reports of prenatal diagnosis of lissencephaly have been published (45–47). It was described that without previous history of an affected child, lissencephaly probably cannot be reliably made until 26 to 28 weeks of gestation (48). However, from recent study in the assessment of Sylvian fissure appearance during pregnancy, there might be a potential of earlier diagnosis of migration disorders (49). Schizencephaly Schizencephaly is a disorder characterized by congenital clefts in the cerebral mantle, lined by pia-ependyma, with communication between the subarachnoid space laterally and the ventricular system medially. Of that 63% is unilateral and 37% bilateral. Frontal region is 44% and frontoparietal is 30% (43). Schizencephaly is associated with ventriculomegaly, microcephaly, polymicrogyria, gray matter heterotopias, dysgenesis of the corpus callosum, absence of the septum pellucidum, and optic nerve hypoplasia. other congenital anomalies Arachnoid Cyst, Interhemispheric Cyst Congenital or acquired cyst, with prevalence of 1% of intracranial masses in newborns, is lined by arachnoid membranes and filled with fluid collection, which is of the same characteristic as the CSF. The number of cysts is mostly single, but two or more cysts can be occasionally observed. Location of arachnoid cyst is various, and it is said that approximately 50% of cysts occurs from the Sylvian fissure (middle fossa), 20% from the posterior fossa, and 10% to 20% each from the convexity, suprasellar, interhemisphere, and quadrigeminal cistern in the pediatric field. Interhemispheric cysts are commonly associated with agenesis or hypogenesis of the corpus callosum. Callosal agenesis with interhemispheric cyst is classified as two types (50). Type I cysts appear to be an extension or diverticulum of the third or lateral ventricles, whereas type 2 cysts are loculated and do not communicate with the ventricular system. Prenatal neuroimaging examples of interhemispheric cyst, middle fossa arachnoid cyst, and suprasellar arachnoid cyst are shown in Figure 8. As intrauterine spontaneous resolution or changing cyst size is often seen during fetal period, serial scanning is important. Detection in the first trimester was 52.8 CLINICAL MATERNAL–FETAL MEDICINE ONLINE Interhemispheric Middlefossa HOSP Dr . POOH GE LOGIQ 9 A G (EDC)=5 M3D USG Suprasellar GA(OPE)=29W.’ HOOP . rD . TREP Dr MRI Figure 8 Prenatal neuroimaging of interhemispheric cyst, middle fossa arachnoid cyst, and suprasellar arachnoid cyst. Abbreviations: USG, ultrasonography; MRI, magnetic resonance imaging. reported (51). Prognosis is generally good. Many are asymptomatic and remain quiescent for years, although others may expand and cause neurologic symptoms by compressing adjacent brain, development of ventriculomegaly, and/or expanding the overlying skull. Brain Tumors Brain tumors are divided into teratomatous, most are the commonly reported brain tumors, and nonteratomatous. Nonteratomatous tumors includes neuroepithelial tumor, such as medulloblastoma, astrocytoma, choroid plexus papilloma, choroid plexus carcinoma, ependymoma, ependymoblastoma, and mesenchymal tumor such as craniopharyngioma, sarcoma, fibroma, hemangioblastoma, hemangioma, and meningioma, and others such as lipoma of the corpus callosum, subependymal giant-cell astrocytoma associated with tuberous sclerosis (often accompanied by cardiac rhabdomyoma) (52). Depending on the site and vascularity, these tumors may lead to macrocrania or local skull swelling, epignathus, secondary hydrocephalus, intracranial hemorrhage, intraventricular hemorrhage, polyhydramnios, and heart failure by high-cardiac output (53) or hydrops. Intracranial masses with solid, cystic, or mixture pattern with or without visualization of hypervascularity can be detected by ultrasound and fetal MRI. Brain tumor should be considered in cases with unexplained intracranial hemorrhage. Craniosynostosis Craniosynostosis is the premature closure of cranial suture, which may affect one or more cranial sutures. Simple sagittal synostosis is most common. Various cranial shapes depend on affected suture(s). Sagittal suture Bilateral coronal suture Unilateral coronal suture Metopic suture Lambdoid suture Unilateral lambdoid suture Coronal/lambdoid/metopic or squamous/sagittal suture Total cranial sutures Scaphocephaly or dolichocephaly Brachycephaly Anterior plagiocephaly Trigonocephaly Acrocephaly Posterior plagiocephaly Cloverleaf skull Oxycephaly Craniosynostosis due to specific syndromes (syndromic craniosynostosis) is usually associated with additional specific features and therefore correct differentiation between these conditions is possible. Examples include Crouzon syndrome (acrocephaly, synostosis of coronal, sagittal and lambdoid sutures and ocular proptosis, maxillary hypoplasia), Apert syndrome (brachycephaly, irregular synostosis, especially coronal suture and midfacial hypoplasia, syndactyly, broad distal phalanx of thumb, and big toe), Pfeiffer syndrome (brachycephaly, synostosis of coronal and/or sagittal sutures 52.9 ASSESSMENT OF FETAL BRAIN ABNORMALITIES 3D B flow Power Doppler Figure 9 Three-dimensional B-flow detection, color Doppler image, and MRI of vein of Galen aneurysmal malformation. and hypertelorism, broad thumbs and toes, and partial syndactyly), and Antley–Bixler syndrome (brachycephaly, multiple synostosis, especially of coronal suture and maxillary hypoplasia, radiohumeral synostosis, choanal atresia, arthrogryposis). Abnormal craniofacial appearance can be detected prenatally by 2D/3D ultrasound (26,54–56). vein of galen aneurysmal malformation It is a congenital malformation of blood vessels of the brain. The main structure is direct arteriovenous fistulas in which blood shunts from choroidal and/or quadrigeminal arteries into an overlying single median venous sac. Vein of Galen aneurysm is not “aneurysm” but “arteriovenous malformation (AVM).” Vein of Galen aneurysmal malformation (VGAM) is a choroidal type of AVM involving the vein of Galen forerunner. This is distinct from an AVM with venous drainage into a dilated, but already formed, vein of Galen (57). Associated anomalies are cardiomegaly, high cardiac output, secondary hydrocephalus, macrocrania, cerebral ischemia (intracranial steal phenomenon), and subarachnoid/cerebral/intraventricular hemorrhages. The 3D B-flow detection, color Doppler image, and MRI of VGAM are shown in Figure 9. Pericallosal Lipoma Intracranial lipomas are congenital malformations composed of mature adipocytes. They are usually located in the midline, particularly in the pericallosal region, a hemispheric location accounting for only 3% to 7% of cases. Two morphologic types of pericallosal lipoma have been described (58,59). Tubulonodular type with generally greater than 2cm in diameter (often smaller than 2cm in fetal period) has a high incidence of corpus callosum dysgenesis, frontal lobe anomalies, and frontal encephaloceles. Curvilinear type, which comprises thin, posteriorly situated lipomas curving around the splenium, is generally associated with a normal corpus callosum and otherwise has a low incidence of associated anomalies. High echogenic mass can be easily demonstrated by ultrasound. Several reports on prenatal diagnosis have been published (60–62). acquired brain abnormalities in utero In terms of encephalopathy or cerebral palsy, “timing of brain insult, antepartum, intrapartum, or postpartum?” is one of the serious controversial issues including medico-sociolegal-ethical problems (15). Although brain insults may relate to antepartum events in a substantial number of term infants with hypoxic-ischemic encephalopathy, the timing of insult cannot always be certain. It is a difficult task to provide a precise prediction of subsequent development of cerebral palsy after a given antepartum event or complication. Fetal heart rate monitoring cannot reveal the presence of encephalopathy, and neuroimaging by ultrasound and MR imaging is the most reliable modality for disclosure of silent encephalopathy. In many cases with cerebral palsy with acquired brain insults, especially term-delivered infants with reactive fetal heart rate tracing and good Apgar score at delivery, recent imaging studies have confirmed the presence of brain insult in utero, suggesting that the majority of cerebral palsy are of antepartum rather than intrapartum in origin. 52.10 CLINICAL MATERNAL–FETAL MEDICINE ONLINE EXP 7.9cm / 1.5 / 13Hz 0004111 GA=32w4d –5 –3 45 TIs 0.1 2010/10/27 8:15:55 PM –2 –3 Default Qual max B114°/V60 3D static 3.0 mm 1 -1 2 3 4 Figure 10 Intracerebral hemorrhage at 32 weeks of gestation. Transvaginal three-dimensional tomographic ultrasound images show unilateral ventriculomegaly due to cerebral hemorrhage and fresh intracerebral hemorrhage (arrows), which is going to change into porencephaly. Intracranial Hemorrhage Intracranial hemorrhage includes subdural hemorrhage, primary subarachnoid hemorrhage, intracerebellar hemorrhage, intraventricular hemorrhage, and intraparenchymal hemorrhage other than cerebellar hemorrhage (63). Hydrocephalus, hydranencephaly, porencephaly, and/or microcephaly are possible secondary complications, which are often detectable by imaging studies. Unilateral ventriculomegaly due to cerebral hemorrhage and fresh intracerebral hemorrhage is shown in Figure 10. The hyperechoic lesion is changing into porencephaly in a short period. Porencephaly Porencephaly or porencephalic cyst is defined as fluid-filled spaces replacing normal brain parenchyma and may or may not communicate with the lateral ventricles or subarachnoid space. The causes may be ischemic episode, trauma (64), demise of one twin, Intracerebral hemorrhage, and infection of cytomegalovirus (65). Some cases in utero have been reported (66,67). Porencephalic cyst never causes a mass effect, which is observed in cases with arachnoid cyst or other cystic mass lesions. This condition is acquired brain insult and differentiated from schizencephaly of migration disorder. fetal periventricular leukomalacia Multifocal areas of necrosis are found deep in the cortical white matter, which are often symmetrical and occur adjacent to the lateral ventricles. Periventricular leukomalacia (PVL) represents a major precursor for neurologic and intellectual impairment, and cerebral palsy in later life. About 25% to 75% of premature infants at autopsy are complicated with periventricular white matter injury. However, clinically, incidence may be much lower. About 5% to 10% of infants have less than 1500g birth weight. In term infants, PVL is very rare. conclusions Recent advances of imaging technology have provided us objective neuroimaging diagnosis as shown in this article. Longitudinal and careful evaluation of neurologic short-term/ long-term prognosis should be required according to precise prenatal diagnosis, for proper counseling and management based on accurate evidence. references 1. Timor-Tritsch IE, Monteagudo A. Transvaginal fetal neurosonography: standardization of the planes and sections by anatomic landmarks. Ultrasound Obstet Gynecol 1996; 8: 42–7. 2. Monteagudo A, Reuss ML, Timor-Tritsch IE. Imaging the fetal brain in the second and third trimesters using transvaginal sonography. Obstet Gynecol 1991; 77: 27–32. 3. Monteagudo A, Timor-Tritsch IE, Moomjy M. In utero detection of ventriculomegaly during the second and third trimesters by transvaginal sonography. Ultrasound Obstet Gynecol 1994; 4: 193–8. 4. Monteagudo A, Timor-Tritsch IE. Development of fetal gyri, sulci and fissures: a transvaginal sonographic study. Ultrasound Obstet Gynecol 1997; 9: 222–8. 5. Pooh RK, Nakagawa Y, Nagamachi N, et al. Transvaginal sonography of the fetal brain: detection of abnormal morphology and circulation. Croat Med J 1998; 39: 147–57. 6. Pooh RK, Maeda K, Pooh KH, Kurjak A. Sonographic assessment of the fetal brain morphology. Prenat Neonat Med 1999; 4: 18–38. 7. Pooh RK, Aono T. Transvaginal power Doppler angiography of the fetal brain. Ultrasound Obstet Gynecol 1996; 8: 417–21. ASSESSMENT OF FETAL BRAIN ABNORMALITIES 8. Pooh RK. Two-dimensional and three-dimensional Doppler angiography in fetal brain circulation. In: Kurjak A, ed. 3D Power Doppler in Obstetrics and Gynecology. Carnforth: Parthenon Publishing, 1999: 105–11. 9. Pooh RK. Three-dimensional ultrasound of the fetal brain. In: Kurjak A, ed. Clinical application of 3D ultrasonography. Carnforth: Parthenon Publishing, 2000: 176–80. 10. Pooh RK, Pooh KH, Nakagawa Y, Nishida S, Ohno Y. Clinical application of three-dimensional ultrasound in fetal brain assessment. Croat Med J 2000; 41: 245–51. 11. Timor-Tritsch IE, Monteagudo A, Mayberry P. Three-dimensional ultrasound evaluation of the fetal brain: the three horn view. Ultrasound Obstet Gynecol 2000; 16: 302–6. 12. Monteagudo A, Timor-Tritsch IE, Mayberry P. Three-dimensional transvaginal neurosonography of the fetal brain: ‘navigating’ in the volume scan. Ultrasound Obstet Gynecol 2000; 16: 307–13. 13. Pooh RK, Nagao Y, Pooh KH. Fetal neuroimaging by transvaginal 3D ultrasound and MRI. Ultrasound Rev Obstet Gynecol 2006; 6: 123–34. 14. Pooh RK, Pooh KH. Fetal neuroimaging with new technology. Ultrasound Rev Obstet Gynecol 2002; 2: 178–81. 15. Pooh RK, Pooh KH. Antenatal assessment of CNS anomalies, including neural tube defects. In: Levene MI, Chervenak FA, eds. Fetal and Neonatal Neurology and Neurosurgery, 4th edn. Elsevier, 2008: 291–338. 16. Pooh RK, Maeda K, Pooh KH. An atlas of fetal central nervous system disease. Diagnosis and Management. London, New York: Parthenon CRC Press, 2003. 17. Pooh RK. Neuroanatomy visualized by 2D and 3D. In: Pooh RK, Kurjak A, eds. Fetal Neurology. New Delhi: Jaypee Brothers Medical Publishers, 2009: 15–38. 18. Pooh RK. Fetal central nervous system. In: Ahmed B, Adra A, Kavak ZN, eds. Donald School Basic Textbook of Ultrasound in Obstetrics and Gynecology. New Delhi: Jaypee Brothers Medical Publishers, 2008: 326–49. 19. Pooh RK, Pooh KH. Fetal neuroimaging. Fetal and Maternal Medicine Review. Volume 19. Cambridge University Press, 2008: 1–31. 20. Blaas HG, Eik-Nes SH, Berg S, Torp H. In-vivo three-dimensional ultrasound reconstructions of embryos and early fetuses. Lancet 1998; 352: 1182–6. 21. Pooh RK. Fetal brain assessment by three-dimensional ultrasound. In: Kurjak A, Kupesic S, eds. Clinical Application Of 3D Sonography. Carnforth, UK: Parthenon Publishing, 2000: 171–9. 22. Pooh RK, Pooh KH. Transvaginal 3D and Doppler ultrasonography of the fetal brain. Semin Perinatol 2001; 25: 38–43. 23. Pooh RK, Pooh KH. The assessment of fetal brain morphology and circulation by transvaginal 3D sonography and power Doppler. J Perinat Med 2002; 30: 48–56. 24. Endres LK, Cohen L. Reliability and validity of three-dimensional fetal brain volumes. J Ultrasound Med 2001; 20: 1265–9. 25. Roelfsema NM, Hop WC, Boito SM, Wladimiroff JW. Three-dimensional sonographic measurement of normal fetal brain volume during the second half of pregnancy. Am J Obstet Gynecol 2004; 190: 275–80. 26. Pooh RK. Neuroscan of congenital brain abnormality. In: Pooh RK, Kurjak A, eds. Fetal Neurology. New Delhi: Jaypee Brothers Medical Publishers, 2009: 59–139. 27. Pooh RK, Pooh KH. Fetal ventriculomegaly. Donald school. J Ultrasound Obstet Gynecol 2007; 2: 40–6. 28. Alagappan R, Browning PD, Laorr A, McGahan JP. Distal lateral ventricular atrium: reevaluation of normal range. Radiology 1994; 193: 405–8. 29. Almog B, Gamzu R, Achiron R, et al. Fetal lateral ventricular width: what should be its upper limit? A prospective cohort study and reanalysis of the current and previous data. J Ultrasound Med 2003; 22: 39–43. 30. Pooh RK, Pooh KH, Nakagawa Y, et al. Transvaginal Doppler assessment of fetal intracranial venous flow. Obstet Gynecol 1999; 93: 697–701. 31. Kelly EN, Allen VM, Seaward G, Windrim R, Ryan G. Mild ventriculomegaly in the fetus, natural history, associated findings and outcome of isolated mild ventriculomegaly: a literature review. Prenat Diagn 2001; 21: 697–700. 32. Goldstein I, Copel JA, Makhoul IR. Mild cerebral ventriculomegaly in fetuses: characteristics and outcome. Fetal Diagn Ther 2005; 20: 281–4. 33. Pilu G, Falco P, Gabrielli S, et al. The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature. Ultrasound Obstet Gynecol 1999; 14: 320–6. 52.11 34. Signorelli M, Tiberti A, Valseriati D, et al. Width of the fetal lateral ventricular atrium between 10 and 12mm: a simple variation of the norm? Ultrasound Obstet Gynecol 2004; 23: 14–18. 35. Ouahba J, Luton D, Vuillard E, et al. Prenatal isolated mild ventriculomegaly: outcome in 167 cases. BJOG 2006; 113: 1072–9. 36. Pilu G, Porelo A, Falco P, Visentin A. Median anomalies of the brain. In: Timor-Tritsch IE, Monteagudo A, Cohen HL, eds. Ultrasonography of the prenatal and neonatal brain, 2nd edn. New York: McGraw-Hill, 2001: 259–76. 37. Volpe JJ. Neural tube formation and prosencephalic development. Neurology of the Neuborn, 4th edn. Philadelphia: WB Saunders, 2001: 3–44. 38. Biggio JR Jr, Wenstrom KD, Owen J. Fetal open spina bifida: a natural history of disease progression in utero. Prenat Diagn 2004; 24: 287–9. 39. Nicolaides KH, Campbell S, Gabbe SG, Guidetti R. Ultrasound screening for spina bifida: cranial and cerebellar signs. Lancet 1986; 2: 72–4. 40. D’Addario V, Pinto V, Del Bianco A, et al. The clivus-supraocciput angle: a useful measurement to evaluate the shape and size of the fetal posterior fossa and to diagnose Chiari II malformation. Ultrasound Obstet Gynecol 2001; 18: 146–9. 41. Barkovich AJ, Kjos BO, Normal D, et al. Revised classification of the posterior fossa cysts and cystlike malformations based on the results of multiplanar MR imaging. AJNR 1989; 10: 977–88. 42. Schwarzler P, Homfray T, Bernard JP, Bland JM, Ville Y. Late onset microcephaly: failure of prenatal diagnosis. Ultrasound Obstet Gynecol 2003; 22: 640–2. 43. Volpe JJ. Neuronal proliferation, migration, organization and myelination. Neurology of the newborn, 4th edn. USA: W.B. Saunders, 2001: 45–99. 44. Kobayashi K, Nakahori Y, Miyake M, et al. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 1998; 394: 388–92. 45. McGahan JP, Grix A, Gerscovich EO. Prenatal diagnosis of lissencephaly: Miller-Dieker syndrome. J Clin Ultrasound 1994; 22: 560–3. 46. Greco P, Resta M, Vimercati A, et al. Antenatal diagnosis of isolated lissencephaly by ultrasound and magnetic resonance imaging. Ultrasound Obstet Gynecol 1998; 12: 276–9. 47. Kojima K, Suzuki Y, Seki K, et al. Prenatal diagnosis of lissencephaly (type II) by ultrasound and fast magnetic resonance imaging. Fetal Diagn Ther 2002; 17: 34–6. 48. Monteagudo A, Timor-Tritsch IE. Fetal Neurosonography of congenital brain anomalies. In: Timor-Tritsch IE, Monteagudo A, Cohen HL, eds. Ultrasonography of the prenatal and neonatal brain, 2nd edn. McGrawHill, New York: 2001: 151–258. 49. Pooh RK. Fetal neuroimaging of neural migration disorder. In: Lazebnik N, Lazebnik RS, eds. Ultrasound Clinics. Volume 3. Elsevier, 2008: 541–52. 50. Barkovich AJ, Simon EM, Walsh CA. Callosal agenesis with cyst: a better understanding and new classification. Neurology 2001; 56: 220–7. 51. Bretelle F, Senat MV, Bernard JP, Hillion Y, Ville Y. First-trimester diagnosis of fetal arachnoid cyst: prenatal implication. Ultrasound Obstet Gynecol 2002; 20: 400–2. 52. Volpe JJ. Brain tumors and vein of Galen malformation. Neurology of the Neuborn, 4th edn. Philadelphia: WB Saunders, 2001: 841–56. 53. Sherer DM, Abramowicz JS, Eggers PC, et al. Prenatal ultrasonographic diagnosis of intracranial teratoma and massive craniomegaly with associated high-output cardiac failure. Am J Obstet Gynecol 1993; 168: 97–9. 54. Pooh RK, Nakagawa Y, Pooh KH, Nakagawa Y, Nagamachi N. Fetal craniofacial structure and intracranial morphology in a case of Apert syndrome. Ultrasound Obstet Gynecol 1999; 13: 274–80. 55. Benacerraf BR, Spiro R, Mitchell AG. Using three-dimensional ultrasound to detect craniosynostosis in a fetus with Pfeiffer syndrome. Ultrasound Obstet Gynecol 2000; 16: 391–4. 56. Faro C, Chaoui R, Wegrzyn P, et al. Metopic suture in fetuses with Apert syndrome at 22–27 weeks of gestation. Ultrasound Obstet Gynecol 2006; 27: 28–33. 57. Lasjaunias PL, Chng SM, Sachet M, et al. The management of vein of Galen aneurysmal malformations. Neurosurgery 2006; 59: S184–94. 58. Tart RP, Quisling RG. Curvilinear and tubulonodular varieties of lipoma of the corpus callosum: an MR and CT study. J Comput Assist Tomogr 1991; 15: 805–10. 52.12 59. Demaerel P, Van de Gaer P, Wilms G, Baert AL. Interhemispheric lipoma with variable callosal dysgenesis: relationship between embryology, morphology, and symptomatology. Eur Radiol 1996; 6: 904–9. 60. Ickowitz V, Eurin D, Rypens F, et al. Prenatal diagnosis and postnatal follow-up of pericallosal lipoma: report of seven new cases. AJNR 2001; 22: 767–72. 61. Jeanty P, Zaleski W, Fleischer AC. Prenatal sonographic diagnosis of lipoma of the corpus callosum in a fetus with Goldenhar syndrome. Am J Perinatol 1991; 8: 89–90. 62. Malinger G, Ben-Sira L, Lev D, et al. Fetal brain imaging: a comparison between magnetic resonance imaging and dedicated neurosonography. Ultrasound Obstet Gynecol 2004; 23: 333–40. CLINICAL MATERNAL–FETAL MEDICINE ONLINE 63. Sherer DM, Anyaegbunam A, Onyeije C. Antepartum fetal intracranial hemorrhage, predisposing factors and prenatal sonography: a review. Am J Perinatol 1998; 15: 431–41. 64. Eller KM, Kuller JA. Porencephaly secondary to fetal trauma during amniocentesis. Obstet Gynecol 1995; 85: 865–7. 65. Moinuddin A, McKinstry RC, Martin KA, Neil JJ. Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection–an illustrative report. Prenat Diagn 2003; 23: 797–800. 66. Meizner I, Elchalal U. Prenatal sonographic diagnosis of anterior fossa porencephaly. J Clin Ultrasound 1996; 24: 96–9. 67. de Laveaucoupet J, Audibert F, Guis F, et al. Fetal magnetic resonance imaging (MRI) of ischemic brain injury. Prenat Diagn 2001; 21: 729–36.