ISUOG Practice Guidelines (updated): sonographic examination of the fetal central nervous system. Part 2: performance of targeted neurosonography

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care, because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG ([email protected]). Details of the grades of recommendation and levels of evidence used in ISUOG Guidelines are given in Appendix 1.

INTRODUCTION

Central nervous system (CNS) malformations are some of the most common congenital abnormalities, with an incidence at birth of 14/10 000 ¹. Neural tube defects are themost frequent CNSmalformation, with a prevalence in pregnancy of 52/100 000². The incidence of intracranial abnormalities with an intact neural tube is uncertain, as most of these abnormalities are likely to escape detection at birth andmanifest only in later life. Long-term follow-up studies suggest, however, that the incidence may be as high as one in 100 births³. During pregnancy, ultrasound screening for CNS malformations is carried out mainly at the time of the mid-trimester anomaly scan⁴ and relies on visualization of three axial planes, namely, the transventricular, transthalamic and transcerebellar planes; basic evaluation of the fetal spine is also part of this screening procedure, and has been described in Part 1 of these guidelines⁵. However, of note is that some malformations may be detectable as early as the first-trimester scan. The focus of this Guideline is to describe the protocol for the diagnostic ultrasound examination that should be performed in any case in which there is an increased risk of CNS malformation. A detailed list of indications for this targeted fetal neurosonography was published in Part 1 of these guidelines⁵. It is commonly accepted that targeted fetal neurosonography has a much greater diagnostic potential than does the basic screening examination, and is particularly helpful in the evaluation of complex malformations^6,7. However, this targeted examination of the fetal CNS requires a high level of expertise that is not always available in many ultrasound facilities, since the method has not yet been implemented universally.

GENERAL CONSIDERATIONS

Recommendation

• The transvaginal approach is the preferred method to perform an adequate high-resolution targeted neurosonographic examination. When this is not technically feasible (e.g. breech presentation; twin pregnancy), the examination is performed transabdominally (GOOD PRACTICE POINT).
• When a transvaginal approach is not technically feasible, the use of high-resolution linear or microconvex transducers (i.e.multiband emission frequency reaching 8–9MHz) is encouraged, because these provide higher resolution than do conventional convex probes (GOOD PRACTICE POINT).

The basis of the neurosonographic examination of the fetal brain is the multiplanar approach, which is obtained by aligning the transducer with the sutures and fontanelles of the fetal head^8–10. When the fetus is in vertex presentation, a transvaginal approach should always be used, because it provides significant advantages over the transabdominal one. In particular, this approach allows both higher resolution, due to the higher emission frequency, and an unobstructed display of sagittal and coronal planes, as the acoustic shadowing produced by the calvarium is circumvented. In fetuses in breech presentation, a transfundal approach is used, positioning the probe on the uterine fundus, parallel instead of perpendicular to the abdomen. However, gentle external version, performed in conjunction with ultrasound examination, is often possible until the early third trimester and should be attempted when technically feasible¹¹. Evaluation of the spine is also part of the neurosonographic examination, and this is performed using a combination of axial, coronal and sagittal planes, as described in Part 1 of these guidelines⁵. During the neurosonographic examination of the spine, the position of the conus medullaris is assessed in the sagittal plane. The neurosonographic examination should include the same measurements as those commonly obtained during a basic examination: biparietal diameter, head circumference, atrial width of the lateral ventricles and the transverse cerebellar diameter. The anteroposterior diameter of the cisterna magna is not measured routinely; it should be measured only if there is suspicion of megacisterna magna. Many nomograms of different brain structures are available and can be used when needed^10,12. The specific measurements obtained may vary depending upon the gestational age and the clinical setting.

NEUROSONOGRAPHIC TECHNIQUE

Fetal brain

Whether the examination is performed transvaginally or transabdominally, proper alignment of the probe along the correct section planes usually requires gentle manipulation of the fetus. A variety of scanning planes can be used, depending upon the position of the fetus10. A systematic evaluation of the brain usually includes visualization of four coronal and three sagittal planes. We present herein a description of the different structures that can be imaged in the second and third trimesters. Apart from the anatomic structures, fetal neurosonography should also include evaluation of the convolutions of the fetal brain, which change throughout gestation^13–17.

• Targeted anatomic assessment of the fetal brain relies on a continuum of sagittal and coronal planes. The key planes are described below, but the trained operator should be able to choose and document those most suited to demonstrating normal/abnormal anatomy (GOOD PRACTICE POINT).

Transfrontal plane (Figure 1a). Visualization of the transfrontal plane is through the anterior fontanelle. It depicts the midline interhemispheric fissure and the frontal lobes of the brain. The plane is anterior to the corpus callosum and therefore demonstrates an uninterrupted interhemispheric fissure. Other structures that appear on the image are the sphenoid bone and, sometimes, the orbits. Late in gestation, the olfactory sulci are also visible^15,18 (Figure 2).
Transcaudate plane (Figure 1b). The transcaudate plane is obtained through a more posterior approach, tilting and/or sliding the transducer towards the posterior edge of the anterior fontanelle. It is one of the most important views in fetal neurosonography. It shows: the frontal horns of the lateral ventricles; the cavum septi pellucidi (a triangular/trapezoid structure below the corpus callosum and between the two frontal horns); the cross-section of the anterior part of the body of the corpus callosum, appearing as a mildly hypoechoic band on top of the cavum septi pellucidi and between the frontal horns; the cerebral falx; the ganglionic eminence; and the caudate nuclei.
Transthalamic plane (Figure 1c). The transthalamic plane is relatively close to the transcaudate plane. It is obtained sometimes through the anterior fontanelle, by angulation of the probe, and sometimes through the open sagittal suture. Both thalami are found in close apposition. The third ventricle may be observed in the midline with the interventricular foramina of Monro; in a slightly more posterior plane, the atrium of the lateral ventricle with choroid plexus appears on each side. Close to the cranial base and in the midline, the basal cistern contains the blood vessels of the circle of Willis and the optic chiasm. This plane also provides a full view of the Sylvian fissures. Evaluation of this latter anatomic landmark is of crucial importance; to image it, it is useful to indent, gently but firmly, the anterior fontanelle, otherwise the lateral shadowing from the parietal bones will impair visualization of the insula and the Sylvian regions.
Transcerebellar plane (Figure 1d). The transcerebellar plane is the only coronal plane that is obtained through the posterior fontanelle. It enables visualization of the occipital horns of the lateral ventricles and the interhemispheric fissure. Depending upon gestational age, the calcarine fissure (Figure 3) and, more deeply, the parieto-occipital fissure, can also be seen. Both cerebellar hemispheres and the vermis are also seen in this plane, in cross-section. The vermis is more echogenic than are the cerebellar hemispheres.

• The midsagittal or median plane is the reference plane for assessing all major midline organs and their anomalies. In order to ensure adequate evaluation of supra- and infratentorial anatomy, this plane should be sought through the anterior or posterior fontanelle, or even the sagittal non-ossified suture, depending on the particular structure of interest. This is achieved by gentle manipulation of the fetal head into the desired position using the free hand (GOOD PRACTICE POINT).

Care should be taken in using corpus callosal biometry to diagnose hypoplasia of the corpus callosum, since a short, thin or thick corpus callosum is not necessarily synonymous with abnormality of this anatomical structure. For this reason, a qualitative assessment is much more important than a quantitative one, i.e. check that all four components of the corpus callosum are visible and sonographically normal (GOOD PRACTICE POINT).
Median or midsagittal anterior plane (Figure 4a). The midsagittal anterior plane is obtained through the anterior fontanelle and enables good visualization of the cerebral midline. When examining the infratentorial structures, an approach through the posterior fontanelle is preferred (see below). This median view shows the corpus callosum with all its components. In particular, the four parts of the corpus callosum – rostrum, genu, body and splenium – and their strict relationship with the cavum septi pellucidi and the cavum vergae,when present, should be visualized. Below the cavum septi pellucidi, the third ventricle can be identified as a hypoechoic structure, but its cranial portion is hyperechogenic due to the presence Figure 2 Transfrontal plane of fetal head. After 26 gestational weeks, olfactory sulci (arrows) can be visualized just above sphenoid bone.

of the tela choroidea. The infratentorial anatomy is also visible in this plane, particularly the vermis and the fourth ventricle. However, to display adequately and assess these structures, it is recommended to use a posterior approach (median or midsagittal posterior plane; see below). Using color Doppler, the anterior cerebral artery, pericallosal arteries with their branches and the vein of Galen may be seen, but its role is marginal in the assessment of the corpus callosum.
Median or midsagittal posterior plane (Figure 5). The midsagittal posterior plane is obtained through the sagittal suture or, better, the posterior fontanelle. Care should be taken to avoid shadowing from the occipital bone onto the posterior fossa and the cisterna magna, which may limit, or make impossible, clinical interpretation of the image. With this posterior approach, the cerebellar vermis is insonated from above and the ultrasound beam is at approximately 90◦ relative to the brainstem, creating the best conditions for visualizing this part of the brain which may be challenging to display on ultrasound. All Figure 5 Midsagittal or median posterior plane is obtained by indenting posterior fontanelle and is best for assessing posterior fossa. Anatomical landmarks seen in this plane: cerebellar vermis (V), with fastigium and fourth ventricle (arrow); cisterna magna ( ); tentorium (double arrow); brainstem (bs) with pons. Sylvian aqueduct (arrowhead) may also be demonstrated.


the anatomical midline landmarks of the vermis and the posterior fossa can be studied thoroughly using this approach. These include: the median plane of the entire vermis, with the fastigium, the primary fissure (and also the secondary fissure, late in pregnancy) and the vermian lobules; the triangular fourth ventricle; the cisterna magna; the brainstem with the midbrain, pons and medulla oblongata. The upper boundary of the posterior fossa, represented by the tentorium, can also be identified. On this median view, it is often possible to visualize fluid in the Sylvian aqueduct, particularly during the second trimester.
Parasagittal planes (Figure 4b). The parasagittal planes are obtained by moving or tilting the transducer slightly laterally from the midsagittal plane, to either side. They depict the lateral ventricles, choroid plexuses, periventricular brain parenchyma and, mainly in the third trimester, the gyri of the cortex, on the convex surface of the brain, as well as a variable portion of the insulae/Sylvian fissures. A more lateral view will enable visualization of the temporal horns of the ventricles and the insulae.
Additional planes. The planes described above represent the key planes to be obtained and evaluated every time a targeted fetal neurosonographic examination is performed. However, according to the focus of the examination, other intermediate sagittal and coronal planes can be displayed and are sometimes very useful. In particular, for example, for a thorough examination of the posterior fossa, additional coronal planes focused on the cross-section of the vermis may be required.

Fetal spine

Recommendation

The ability to visualize the conus medullaris lying on the ventral border of the spinal canal, close to the vertebral bodies, is a good hint to determine the normality of the lumbosacral spine (GOOD PRACTICE POINT).

Three scanning planes can be used to evaluate the integrity of the spine. The choice depends upon the fetal position. Usually, only two of these scanning planes are possible in any given case, but manipulation of the fetus or three-dimensional (3D) ultrasound can be used to obtain the third plane when needed.
Transverse or axial planes. In transverse or axial planes, the examination of the spine is a dynamic process, performed by sweeping the transducer along the entire length of the spine, while remaining within the axial plane of the level being examined (Figure 6). The vertebrae have different anatomic configurations at different levels: fetal thoracic and lumbar vertebrae have a triangular shape, with the ossification centers surrounding the neural canal; the cervical vertebrae are quadrangular in shape; and sacral vertebrae are flat.
Sagittal planes. In sagittal planes, the ossification centers of the vertebral body and posterior arches form two parallel lines that converge in the sacrum. When the fetus is prone, a true sagittal section can also be obtained, Figure 6 Axial views of fetal spine at different levels: (a) cervical; (b) thoracic; (c) lumbar; (d) sacral. Arrows indicate the three ossification centers of a vertebra. Note intact skin overlying spine. In (a–c), spinal cord is visible as hypoechoic ovoid with central white dot (arrowhead).


by directing the ultrasound beam across the non-ossified spinous process. This allows imaging of the spinal canal and of the spinal cord within it (Figure 7). In the late second and third trimesters, the conus medullaris is usually found at the level of the second/third lumbar vertebrae (L2–L3)^19–21. Integrity of the neural canal is also inferred from the regular disposition of the ossification centers of the spine and the presence of soft tissue covering the spine. If a true sagittal section can be obtained, visualizing the conus medullaris in its normal location further strengthens the diagnosis of normality (Figure 7).

Recommendation

The use of high-frequency transabdominal linear/ microconvex transducers enhances the assessment of the spinal cord and conus medullaris in the midsagittal view of the spine (GOOD PRACTICE POINT).

Three-dimensional ultrasound

Recommendation

The use of a 3D ultrasound approach is recommended in targeted neurosonography, particularly when a good two-dimensional image is difficult to obtain, in order to benefit from both the enhanced resolution and the possibility of performing multiplanar imaging correlation (GOOD PRACTICE POINT).

While there are some useful landmarks ensuring adequacy of a midsagittal/median plane of the fetal brain (e.g. corpus callosum and vermis), it is not uncommon for minor deviation from the perfect midsagittal view to go unnoticed by the operator. This, in turn, may affect not only measurements but also qualitative assessment of the brain and brainstem. The employment of 3D ultrasound for targeted neurosonography may, therefore, Figure 7 Sagittal view of fetal spine. Using unossified spinous process of vertebrae as acoustic window, contents of neural canal are demonstrated. After 20weeks, conus medullaris (arrow) is normally positioned at level of second/third lumbar vertebrae (L2–L3), leaving, dorsally, triangular zone filled with cerebrospinal fluid. Note continuity of skin (arrowheads). Figure 8 Coronal view of fetal spine (arrows). This plane is useful to rule out hemivertebrae and diastematomyelia. It can be obtained at level of vertebral bodies (a) or, more posteriorly, at level of arches (b). Objective is to rule out abnormal angling of spine.

be particularly useful, contributing in two main ways. First, by using multiplanar image correlation, it is possible to obtain perfectly aligned views on the three orthogonal planes (Figure 9); second, the possibility of displaying thicker ‘slices’ of the brain increases the signal-to-background noise ratio on all three planes, with significant enhancement of image quality. These advantages support our recommendation to use a 3D approach to neurosonography^7,22,23. In addition, assessment of the fetal spine benefits from 3D rendering and reconstruction of the coronal planes at the level of the vertebral bodies and/or posterior arches24 (Figure 10).

Neurosonography at 13–17 gestational weeks

Introduction into clinical practice of high-frequency transducers^25–28 and the increasing trend to perform

an anatomic evaluation earlier in gestation, also recommended by ISUOG, amongst others^29–31, have led to early referrals for suspicion of brain or spinal malformations. However, the advanced assessment of the fetal brain at 13–14 gestational weeks differs somewhat from that at 15–17weeks, owing to the rapid changes that the fetal CNS undergoes around these gestational ages.
The recommended approach is to use transvaginal ultrasound. Although the newer high-frequency transabdominal transducers allow an adequate early neurosonographic examination, especially if the maternal body mass index is ≤25 kg/m2 and the focus of the examination is not the posterior fossa, use of higher-frequency transvaginal transducers (6–12 MHz) leads to significant enhancement in the display of early fetal cerebral anatomy and allows more thorough assessment of this anatomic region. The approach of choice at 13–14 weeks of gestation includes assessment of the axial transventricular (Figure 11a) and transthalamic (Figure 11b) planes, in association with the midsagittal plane (Figure 11c) reconstructed from 3D volume datasets that are acquired, unlike in later gestation, from an axial view of the fetal head. This is possible due to the significantly lower degree of ossification of the fetal skull at this early gestational age. This, combined with the use of multiplanar imaging, leads to perfect midsagittal and coronal images of the ventricular system and the whole brain, although attention at this gestational age is often focused mainly on the diencephalon and posterior fossa (Figure 11c,d)31. The need to assess the axial planes is related to the mounting body of evidence supporting the early diagnosis of open spina bifida32,33. All sonographic signs described are due to the leakage of cerebrospinal fluid through the open dysraphism. The key views to detect these signs are the transventricular plane^34,35 (Figure 11a) and the posterior midsagittal one^29,32 (Figure 11c). The latter is also the reference plane for the early assessment of cystic vermian abnormalities^31,36; such an assessment has to be undertaken with great caution, particularly when these abnormalities are apparently isolated, due to

the high risk of false-positive diagnoses³⁷. Should there be any suspicion of open spina bifida, direct evidence of the malformation should then be obtained with a high-resolution transvaginal assessment of the fetal spine.
At 15–17 gestationalweeks, the recommendation to use the transvaginal approach remains, enabling evaluation of structures not seen at earlier ages^10,38,39. Preferred acquisition planes are coronal and sagittal ones, due to the position of the head facilitating a transfontanellar/sagittal suture approach (Figure 12). The axial planes are obtained either using the transabdominal approach, using the transvaginal approach with manipulation of the fetal head, or using 3D reconstructions.
Transventricular plane. At 13–14 gestational weeks, the transventricular plane allows assessment of the amount of cerebrospinal fluid around the choroid plexuses, the midline and the thin layer of developing brain parenchyma around the lateral ventricle (Figure 11a). At 15–17 gestational weeks, more information can be gathered about the brain parenchyma and the ventricular system. It should also be underlined that an oval anechogenic structure is often evident at this gestational age, along the midline (Figure 12a). It was demonstrated recently that this structure, formerly thought to represent the third ventricle, is in fact the cavum veli interpositi (Figure 12), and that it is rather common, being visible in almost half of fetuses at 13–17 gestational weeks³⁸.
Midsagittal/median view. At 13–14 gestational weeks, the reconstructed midsagittal/median plane allows complete assessment of the ventricular system, since the aqueduct is much more prominent than it is later in gestation (Figure 11c). In addition, this is the best approach to assess the infratentorial anatomy in cases in which a ‘cystic posterior fossa’ (mostly a normal finding related to the development of these structures) is detected at nuchal translucency screening³¹. In some cases, starting from 14–17 gestational weeks, the first evidence of the cavum septi pellucidi³⁸ and the anterior portions of the corpus callosum can be visualized³⁹ (Figure 12d). In the posterior fossa, the anatomy of the developing cerebellar vermis and the brainstem can be studied. The operator should be aware of the fact that, at this gestational age, the appearance of the cerebellum is completely different from that which we are used to seeing during the 18–23-week examination. An example is the fourth ventricle, which is continuous, initially, with the Blake’s pouch, and, when the Blake’s pouch ruptures to create the Magendie foramen, with the cisterna magna (Figures 11 and 12)^40,41.
Even though the potential of the early anatomical assessment has increased considerably, for most CNS abnormalities, a follow-up neurosonographic

examination after 20weeks of gestation is warranted. Significant exceptions, with straightforward diagnosis and no need for a follow-up scan, are the lethal or near-lethal anomalies, such as exencephaly-anencephaly, gross cephalocele and holoprosencephaly.

FETAL BRAIN MRI

Recommendation

Fetal brain magnetic resonance imaging (MRI) is considered complementary to neurosonography; it can add significant clinical information when requested to answer specific questions posed by the neurosonologist that the targeted fetal CNS evaluation could not answer. When neurosonographic evaluation is unavailable or the level of performance inadequate, it can replace neurosonography as the second-line evaluation, as long as the operator has sufficient training in fetal brainMRI (GOOD PRACTICE POINT).
ISUOG guidelines for the performance and reporting of fetal MRI are available and provide useful information on this technique⁴². It should be underlined that, when the indication for this complementary imaging modality is appropriate, and the diagnostic query specified clearly, MRI may contribute significantly to the final diagnosis. However, MRI should be performed only after, and to complement, a neurosonographic examination, if this is considered to be indicated by the trained operator in order to address a relevant diagnostic or clinical query. Published evidence indicates that, when an adequate neurosonographic examination is carried out by an experienced operator, according to the criteria specified in this Guideline, a MRI examination is required in only 7–15% of cases^43–45. It is important, both for the sake of the patient and to avoid inappropriate referral, not to rush from suspicion of CNS malformation on screening ultrasound, or on suboptimal neurosonography not meeting the technical criteria described herein, to MRI^42,46.

GUIDELINE AUTHORS

This Guideline was produced on behalf of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) by the following authors, and peer reviewed by the Clinical Standards Committee.
D. Paladini, Fetal Medicine and Surgery Unit, Istituto G. Gaslini, Genoa, Italy
G. Malinger, Division of Ultrasound in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Centre, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
R. Birnbaum, Division of Ultrasound in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Centre, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
A. Monteagudo, Carnegie Imaging for Women, Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA
G. Pilu, Obstetric Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
L. J. Salomon, Hˆ opital Necker Enfants Malades, AP-HP, and LUMIERE platform, EA 7328 Universit e de Paris, Paris, France
I. E. Timor-Tritsch, Division of Obstetrical and Gynecological Ultrasound, NYU School of Medicine, New York, NY, USA

CITATION

This Guideline should be cited as: ‘Paladini D, MalingerG, Birnbaum R, Monteagudo A, Pilu G, Salomon LJ, Timor-Tritsch IE. ISUOG Practice Guidelines (updated): sonographic examination of the fetal central nervous system. Part 2: performance of targeted neurosonography. Ultrasound Obstet Gynecol 2021. https://doi.org/10.1002/uog.23616.

REFERENCES

1. Tagliabue G, Tessandori R, Caramaschi F, Fabiano S, Maghini A, Tittarelli A, Vergani D, Bellotti M, Pisani S, Gambino ML, Frassoldi E, Costa E, Gada D, Crosignani P, Contiero P. Descriptive epidemiology of selected birth defects, areas of Lombardy, Italy, 1999. Popul Health Metr 2007; 5: 4.
2. Atta CA, Fiest KM, Frolkis AD, Jette N, Pringsheim T, St Germaine-Smith C, Rajapakse T, Kaplan GG, Metcalfe A. Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis. Am J Public Health 2016; 106: e24–34.
3. Myrianthopoulos NC. Epidemiology of central nervous system malformations. In Handbook of Clinical Neurology. Vinken PJ, Bruyn GW (eds). Elsevier: Amsterdam, 1977; 139–171.
4. Salomon LJ, Alfirevic Z, Berghella V, Bilardo C, Hernandez-Andrade E, Johnsen SL, Kalache K, Leung KY, Malinger G, Munoz H, Prefumo F, Toi A, Lee W, Committee ICS. Practice guidelines for performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol 2011; 37: 116–126.
5. Malinger G, Paladini D, Haratz KK, Monteagudo A, Pilu GL, Timor-Tritsch IE. ISUOG Practice Guidelines (updated): sonographic examination of the fetal central nervous system. Part 1: performance of screening examination and indications for targeted neurosonography. Ultrasound Obstet Gynecol 2020; 56: 476–484.
6. Malinger G, Birnbam R, Haratz KK. Dedicated neurosonography for recognition of pathology associated with mild-to-moderate ventriculomegaly. Ultrasound Obstet Gynecol 2020; 56: 319–323.
7. 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: 307–313.
8. Malinger G, Katz A, Zakut H. Transvaginal fetal neurosonography. Supratentorial structures. Isr J Obstet Gynecol 1993; 4: 1–5.
9. Timor-Tritsch IE, Monteagudo A. Transvaginal fetal neurosonography: standardization of the planes and sections by anatomic landmarks. Ultrasound Obstet Gynecol 1996; 8: 42–47.
10. Timor-Tritsch IE, Monteagudo A, Pilu G, Malinger G. Ultrasonography of the fetal brain. McGraw-Hill: New York, 2012.
11. Paladini D, Donarini G, Rossi A. Indications for MRI in fetal isolated mild ventriculomegaly . . . ‘And then, there were none’. Ultrasound Obstet Gynecol 2019; 54: 151–155. 12. Napolitano R, Molloholli M, Donadono V, Ohuma EO, Wanyonyi SZ, Kemp B, Yaqub MK, Ash S, Barros FC, Carvalho M, Jaffer YA, Noble JA, Oberto M, Purwar M, Pang R, Cheikh Ismail L, Lambert A, Gravett MG, Salomon LJ, Bhutta ZA, Kennedy SH, Villar J, Papageorghiou AT, International F, Newborn Growth Consortium for the 21st C. International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project. Ultrasound Obstet Gynecol 2020; 56: 359–370.
13. Droulle P, Gaillet J, Schweitzer M. [Maturation of the fetal brain. Echoanatomy: normal development, limits and value of pathology]. J Gynecol Obstet Biol Reprod 1984; 13: 228–236.
14. Monteagudo A, Timor-Tritsch IE. Development of fetal gyri, sulci and fissures: a transvaginal sonographic study. Ultrasound Obstet Gynecol 1997; 9: 222–228.
15. Cohen-Sacher B, Lerman-Sagie T, Lev D, Malinger G. Developmental milestones of the fetal cerebral cortex. A longitudinal sonographic study. Ultrasound Obstet Gynecol 2006; 27: 494–502.
16. Toi A, Chitayat D, Blaser S. Abnormalities of the foetal cerebral cortex. Prenat Diagn 2009; 29: 355–371.
17. Poon LC, Sahota DS, Chaemsaithong P, Nakamura T, Machida M, Naruse K, Wah YM, Leung TY, Pooh RK. Transvaginal three-dimensional ultrasound assessment of Sylvian fissures at 18–30 weeks’ gestation. Ultrasound Obstet Gynecol 2019; 54: 190–198.
18. Acanfora MM, Stirnemann J, Marchitelli G, Salomon LJ, Ville Y. Ultrasound evaluation of development of olfactory sulci in normal fetuses: a possible role in diagnosis of CHARGE syndrome. Ultrasound Obstet Gynecol 2016; 48: 181–184.
19. Perlitz Y, Izhaki I, Ben-Ami M. Sonographic evaluation of the fetal conus medullaris at 20 to 24 weeks’ gestation. Prenat Diagn 2010; 30: 862–864.
20. MottetN, Saada J, Jani J,Martin A, RiethmullerD, Zerah M, Benachi A. Sonographic Evaluation of Fetal Conus Medullaris and Filum Terminale. Fetal Diagn Ther 2016; 40: 224–230.
21. Rodriguez MA, Prats P, Rodriguez I, Comas C. Prenatal Evaluation of the Fetal Conus Medullaris on a Routine Scan. Fetal Diagn Ther 2016; 39: 113–116.
22. Fratelli N, Taddei F, Prefumo F, Franceschetti L, Farina G, Frusca T. Interobserver reproducibility of transabdominal 3-dimensional sonography of the fetal brain. J Ultrasound Med 2009; 28: 1009–1013.
23. Maiz N, Alonso I, Belar M, Burgos J, Irasarri A, Molina FS, de Paco C, Pijoan JI, Plasencia W, Rodo C, Rodriguez MA, Tajada M, Tubau A. Three dimensional ultrasonography for advanced neurosonography (Neurosofe-3d). Analysis of acquisition-related factors influencing the quality of the brain volumes. Prenat Diagn 2016; 36: 1054–1060.
24. Buyukkurt S, Binokay F, Seydaoglu G, Gulec UK, Ozgunen FT, Evruke C, Demir C. Prenatal determination of the upper lesion level of spina bifida with three-dimensional ultrasound. Fetal Diagn Ther 2013; 33: 36–40.
25. Bronshtein M, Blumenfeld Z. Transvaginal sonography-detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters. Prenat Diagn 1992; 12: 587–593.
26. Pooh RK. Neurosonoembryology by three-dimensional ultrasound. Semin Fetal Neonatal Med 2012; 17: 261–268.
27. Rottem S, Bronshtein M, Thaler I, Brandes JM. First trimester transvaginal sonographic diagnosis of fetal anomalies. Lancet 1989; 1: 444–445.
28. Votino C, Kacem Y, Dobrescu O, Dessy H, Cos T, Foulon W, Jani J. Use of a high-frequency linear transducer and MTI filtered color flow mapping in the assessment of fetal heart anatomy at the routine 11 to 13 + 6-week scan: a randomized trial. Ultrasound Obstet Gynecol 2012; 39: 145–151.
29. Chaoui R, Nicolaides KH. From nuchal translucency to intracranial translucency: towards the early detection of spina bifida. Ultrasound Obstet Gynecol 2010; 35: 133–138.
30. Salomon LJ, Alfirevic Z, Bilardo CM, Chalouhi GE, Ghi T, Kagan KO, Lau TK, Papageorghiou AT, Raine-Fenning NJ, Stirnemann J, Suresh S, Tabor A, Timor-Tritsch IE, Toi A, Yeo G. ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol 2013; 41: 102–113.
31. Paladini D, Donarini G, Parodi S, Chaoui R. Differentiating features of posterior fossa at 12-13 weeks’ gestation in fetuses with Dandy-Walker malformation and Blake’s pouch cyst. Ultrasound Obstet Gynecol 2019; 53: 850–852.
32. Chen FC, Gerhardt J, Entezami M, Chaoui R, Henrich W. Detection of Spina Bifida by First Trimester Screening - Results of the Prospective Multicenter Berlin IT-Study. Ultraschall Med 2017; 38: 151–157.
33. Meller C, Aiello H, Otano L. Sonographic detection of open spina bifida in the first trimester: review of the literature. Childs Nerv Syst 2017; 33: 1101–1106.
34. Chaoui R, Benoit B, Entezami M, Frenzel W, Heling KS, Ladendorf B, Pietzsch V, Sarut Lopez A, Karl K. Ratio of fetal choroid plexus to head size: simple sonographic marker of open spina bifida at 11–13weeks’ gestation. Ultrasound Obstet Gynecol 2020; 55: 81–86.
35. Ushakov F, Sacco A, Andreeva E, Tudorache S, Everett T, David AL, Pandya PP. Crash sign: new first-trimester sonographicmarker of spina bifida. Ultrasound Obstet Gynecol 2019; 54: 740–745.
36. Volpe P, Persico N, Fanelli T, De Robertis V, D’Alessandro J, Boito S, Pilu G, Votino C. Prospective detection and differential diagnosis of cystic posterior fossa anomalies by assessing posterior brain at 11–14 weeks. Am J Obstet Gynecol MFM 2019; 1: 171–183.
37. Malinger G, Lev D, Lerman-Sagie T. The fetal cerebellum. Pitfalls in diagnosis and management. Prenat Diagn 2009; 29: 372–380.
38. Birnbaum R, Barzilay R, Brusilov M, Wolman I, Malinger G. The normal cavum veli interpositi at 14-17 weeks: three-dimensional and Doppler transvaginal neurosonographic study. Ultrasound Obstet Gynecol 2020. DOI: 10.1002/uog .22176.
39. Birnbaum R, Barzilay R, Brusilov M, Wolman I, Malinger G. The early pattern of human corpus callosum development: A transvaginal 3D neurosonographic study. Prenat Diagn 2020; 40: 1239–1245.
40. Babcook CJ, Chong BW, Salamat MS, Ellis WG, Goldstein RB. Sonographic anatomy of the developing cerebellum: normal embryology can resemble pathology. AJR Am J Roentgenol 1996; 166: 427–433.
41. Contro E, Volpe P, De Musso F, Muto B, Ghi T, De Robertis V, Pilu G. Open fourth ventricle prior to 20 weeks’ gestation: a benign finding? Ultrasound Obstet Gynecol 2014; 43: 154–158.
42. Prayer D, Malinger G, Brugger PC, Cassady C, De Catte L, De Keersmaecker B, Fernandes GL, Glanc P, Goncalves LF, Gruber GM, Laifer-Narin S, LeeW,Millischer AE, Molho M, Neelavalli J, Platt L, Pugash D, Ramaekers P, Salomon LJ, Sanz M, Timor-Tritsch IE, Tutschek B, Twickler D, Weber M, Ximenes R, Raine-Fenning N. ISUOG Practice Guidelines: performance of fetal magnetic resonance imaging. Ultrasound Obstet Gynecol 2017; 49: 671–680.
43. Malinger G, Ben-Sira L, Lev D, Ben-Aroya Z, Kidron D, Lerman-Sagie T. Fetal brain imaging: a comparison between magnetic resonance imaging and dedicated neurosonography. Ultrasound Obstet Gynecol 2004; 23: 333–340.
44. Paladini D, Quarantelli M, Sglavo G, Pastore G, Cavallaro A, D’Armiento MR, Salvatore M, Nappi C. Accuracy of neurosonography and MRI in clinical management of fetuses referred with central nervous system abnormalities. Ultrasound Obstet Gynecol 2014; 44: 188–196.
45. Malinger G, Paladini D, Pilu G, Timor-Tritsch IE. Fetal cerebral magnetic resonance imaging, neurosonography and the brave new world of fetal medicine. Ultrasound Obstet Gynecol 2017; 50: 679–680.
46. Di Mascio D, Sileo FG, Khalil A, Rizzo G, Persico N, Brunelli R, Giancotti A, Panici PB, Acharya G, D’Antonio F. Role of magnetic resonance imaging in fetuses with mild or moderate ventriculomegaly in the era of fetal neurosonography: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2019; 54: 164–171.

APPENDIX 1 Grades of recommendation and levels of evidence used in ISUOG Guidelines

Classification of evidence levels

Grades of recommendation