Ultrasound Obstet Gynecol 2004; 24: 706–715 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/uog.1802 How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development? A. TOI*, W. S. LISTER† and K. W. FONG* *Department of Medical Imaging, Mount Sinai Hospital, University of Toronto, Toronto and †Department of Medical Imaging, Peach Arch Hospital, White Rock, British Columbia, Canada K E Y W O R D S: anatomy; brain; fetus; neurodevelopment; normal; ultrasound ABSTRACT Objectives To evaluate the time of appearance and pattern of development of fetal cerebral sulci at prenatal ultrasound. Methods We studied 50 normal fetuses for visibility of cerebral sulci, especially sulci which appear early in anatomical studies, namely the parieto-occipital fissure, calcarine sulcus, cingulate sulcus, convexity sulci and insula/Sylvian fissure. The gestational ages of the fetuses studied ranged from 15.6 to 29.6 weeks. Results Sulci could be seen by transabdominal ultrasound as early as 18.5 weeks. Medial hemispheric sulci and the insula were visible earlier and more confidently than convexity sulci. The earliest gestational ages at which specific sulci could be seen in any fetus were as follows: parieto-occipital fissure 18.5 weeks, calcarine sulcus 18.5 weeks, cingulate sulcus 23.2 weeks and convexity sulci 23.2 weeks. In the present series, the gestational ages at which these sulci were always visible were as follows: parieto-occipital fissure > 20.5 weeks, calcarine sulcus > 21.9 weeks, cingulate sulcus > 24.3 weeks and convexity sulci > 27.9 weeks. The insula and its margin (the circular sulcus) and the overgrowing opercula undergo characteristic maturation. The circular sulcus at the margin of the insula was initially smooth but started becoming angular after about 17 weeks as it started to be overgrown by the parietal and temporal lobe opercula. Initially the insula/operculum angle was obtuse. An acute angle was first evident at 23.2 weeks and in all fetuses older than 24.5 weeks. Our ultrasound data were consistent with anatomical studies and fetal magnetic resonance imaging findings. Conclusions Some cerebral sulci can be seen at prenatal ultrasound as early as 18.5 weeks. Familiarity with the normal pattern of sulcal development and the discriminating gestational ages for the appearance of different sulci may allow early suspicion of lissencephaly. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION The ultrasound literature suggests that the prenatal ultrasound diagnosis of lissencephaly is not possible until 27–28 weeks1 – 3 . However, anatomical and magnetic resonance imaging (MRI) studies have shown that cerebral sulci start developing much earlier. Anatomical studies show that some sulci on the medial apposed surfaces of the hemispheres, which we collectively call the medial hemispheric sulci, can be seen by 16–19 weeks4,5 . These medial hemispheric sulci include the parieto-occipital fissure, calcarine sulcus and cingulate sulcus. Also, at fetal MRI examinations, medial hemispheric sulci are reported to appear as early as 18–20 weeks6,7 . Convexity sulci, namely those on the outer convex surfaces of the cerebral hemispheres, appear later and are seen by 20–24 weeks on anatomical studies4,5 and by about 24–27 weeks at MRI6 – 10 . We include as convexity sulci the central sulcus, superior temporal sulcus and any other sulcus on the outer convex brain surface. Our objective was to establish the pattern of early normal fetal cerebral sulcal development by prenatal ultrasound prior to 30 weeks’ gestation. We felt that such data could lead to the suspicion of abnormalities of cortical development such as lissencephaly on ultrasound performed before 27 weeks. Correspondence to: Dr A. Toi, Ultrasound Department, Mount Sinai Hospital, 3rd Floor, Ontario Power Generation Building, 700 University Avenue, Toronto, Ontario, Canada M5G 1X7 (e-mail: atoi@mtsinai.on.ca) Accepted: 28 October 2004 Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER Normal fetal sulci METHODS We studied patients referred for obstetric ultrasound between 15 and 30 weeks’ gestation. Ultrasound scans were performed by a single operator. Patients were included if the fetal anatomy appeared normal or only minor ultrasound markers were present. Gestational age was determined by ultrasound biometry (average of biparietal diameter, abdominal circumference and femur length) at time of the study scan and was consistent with stated menstrual dates or age as established by the first-trimester scan if menstrual history was uncertain. Birth and newborn records were reviewed after delivery. Approval for the study was granted by the institutional research ethics board. Detailed views of the fetal head and brain were obtained transabdominally using Philips/ATL HDI 5000 ultrasound machine with 7 or 5 MHz curved array (C7–4 or C5–2) transducers (Philips/ATL, Bothell, WA, USA). Transvaginal scanning was not performed since the transabdominal scans provided adequate visibility of the brain and sulci in all the study cases. We evaluated specifically those sulci and fissures which have been reported to appear relatively early on anatomical studies, namely the parieto-occipital fissure, the calcarine, cingulate and convexity sulci and also the insula/Sylvian fissure4,5,11 (Figure 1). Axial, coronal, sagittal and oblique views were used as needed to access sulci. A sulcus was defined as being present if a distinct notch or indentation could be seen in the expected area of the sulcus. We defined ‘convexity sulcus’ as any sulcus visible as an indentation on the outer convex hemispheric surface. The Sylvian fossa was best assessed in the axial orientation. The insular margin, the circular sulcus, was judged to be smooth or angular. When angular, the angle was further defined to be obtuse if the angle between the insula and the temporal lobe operculum was greater than 90◦ and acute if the angle was less than 90◦ . RESULTS Fifty scans in 46 fetuses were included. Forty-two fetuses were scanned once and four fetuses twice at different gestational ages. Gestational ages ranged from 15.6 to 29.6 weeks. Fetal numbers in different age groups were as follows: < 18 weeks (n = 4), 18–19.9 weeks (n = 21), 20–21.9 weeks (n = 8), 22–23.9 weeks (n = 6), > 24 weeks (n = 11). The indications for ultrasound scan were as follows: routine (n = 19), anomaly history (n = 10), suspected abnormality at ultrasound done elsewhere (n = 8), maternal disease (n = 4), positive maternal serum screen (n = 4), increased first-trimester nuchal translucency (n = 3), biophysical profile (n = 2). All the fetuses had normal appearing heads and brains. Extracranial anatomy was completely normal in 44 fetuses. Six fetuses showed markers or minor findings as follows: isolated echogenic intracardiac focus (n = 4), isolated choroid plexus cyst (n = 1), both choroid plexus cyst and echogenic intracardiac focus (n = 1). All of these Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. 707 (a) Cingulate Parietooccipital Calcarine (b) Convexity sulci Figure 1 Medial hemispheric (a) and lateral convexity (b) surfaces of 26-week fetal brain showing the sulci which appear early and can be recognized at prenatal ultrasound. On the medial hemispheric surface note the cingulate sulcus, parieto-occipital fissure and calcarine sulcus. On the lateral convexity surface note the convexity sulci above and behind the Sylvian fossa (sf). Figure modified and reproduced, with permission, from Dorovini-Zis K, Dolman CL, Gestational development of brain, Arch Pathol Lab Med 1977; 101: 192. Copyrighted 1977, American Medical Association. All rights reserved. fetuses had normal newborn examinations by experienced pediatricians after delivery. We found that sulci were easier to detect enface in a direction perpendicular to their plane of orientation. The sulci on the hemisphere farther from the transducer were seen more clearly than those in the near field. In general, the sulci on the medial surfaces of the hemispheres, specifically the parieto-occipital fissure, calcarine sulcus and cingulate sulcus, appeared earlier and were more confidently seen than convexity sulci. The earliest appearance of a sulcus was as a small ‘dot’ in the expected site of the sulcus. Later, the sulci formed an obvious ‘V’ indentation. Finally, the sulci became deeper and were visible as a surface notch and an echogenic line extending into the brain matter in a ‘Y’ configuration. Similar appearances and progression are reported at anatomical and MRI studies4,10,12 . Ultrasound Obstet Gynecol 2004; 24: 706–715. Toi et al. 708 In the present study we noted the youngest age at which a specific sulcus was first visible in any fetus and also the age after which the sulcus was visible in all fetuses. The parieto-occipital fissure was best imaged axially in a plane near the upper margin of the occipital horns of the lateral ventricles. It first appeared at 18.5 weeks, and was always visible after 20.5 weeks (Figure 2). The calcarine sulcus was best imaged in a coronal plane through the occipital lobes. It could be seen as early as 18.5 weeks and was always visible after 21.9 weeks (Figure 3). The cingulate sulcus was generally not as confidently seen. It was best imaged in a coronal plane above the region of the thalami. (a) It became visible by 23.2 weeks in some fetuses and was always seen after 24.3 weeks (Figure 4). Convexity sulci were seen with more difficulty and were the last to be seen with confidence. They were best imaged semi-axially by exploiting the window offered by the proximal squamosal bony suture and then angling the plane of the scan on the farther brain surface from the approximate level of the insula superiorly. The late detection of convexity sulci is likely to be due to their initial development in the high parietal regions where ultrasound access is obstructed by cranial bones. Convexity sulci could first be seen in some fetuses by 23.2 weeks in the parietal and temporal regions but were confidently seen only in fetuses older than 27.9 weeks (Figure 5). The earliest detected convexity sulci were on the outer convex peripheral hemispheric surface posterior or superior to the Sylvian fissure and were (e) 15 20 25 30 Gestational age (weeks) Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. Figure 2 Parieto-occipital fissure. (a) Optimal axial plane of section through brain to show parieto-occipital fissure. (b) Ultrasound image of a 17-week fetus showing smooth medial hemispheric brain surface (arrow) before formation of the parieto-occipital fissure. (c) Ultrasound image of an 18.7-week fetus showing earliest indication of the parieto-occipital fissure as a small dot on the near and far hemispheric surface (arrow). (d) Ultrasound image of a 24.3-week fetus with more advanced fissure development (arrows) giving a diamond shape. (e) Graph illustrating the visibility of the parieto-occipital fissure in individual fetuses at different gestational ages. , visible; , not visible; , unable to assess. Ultrasound Obstet Gynecol 2004; 24: 706–715. Normal fetal sulci 709 (a) c Figure 3 Calcarine sulcus. (a) Optimal coronal plane of section through the occipital lobe of the fetal brain to demonstrate the calcarine sulcus. (b) Ultrasound image of an 18.9-week fetus showing smooth medial surface of the occipital lobe before calcarine sulcus formation (arrow). (c) Ultrasound image of a 21.7-week fetus with minimal calcarine sulcus formation visible as a small dot on the brain surface (arrow). (d) Ultrasound image of a 23.6-week fetus showing more advanced calcarine sulcus development (arrow). (e) Graph illustrating the visibility of the calcarine sulcus in individual fetuses at different gestational ages. , visible; , not visible; , unable to assess. (e) 15 20 25 30 Gestational age (weeks) likely to be the superior temporal, central and postcentral sulci. When imaged in a direction parallel to their plane of orientation, sulci appeared as an echogenic plate that should not be mistaken for a disorder of the brain parenchyma. This is especially true of the calcarine sulcus, which on axial views can be seen as an echogenic band on the medial surface of the occipital lobe just medial to the occipital horn (Figure 6). Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. The insula/Sylvian fissure showed a characteristic pattern of development (Figure 7). In early pregnancy the Sylvian fossa was a smoothly margined indentation. After about 17 weeks’ gestation the smooth Sylvian fossa indentation developed angular margins at the site of the developing circular sulcus. This resulted in a plateau-like appearance with angularity at the margins (the circular sulcus) where the insula meets the frontal, parietal and temporal opercula anteriorly, superiorly and posteriorly. These angles were initially obtuse but became acute as the opercula progressively overgrew the insula and eventually met to form the closed Sylvian fissure. Acute insula/operculum angles could be seen as early as 23.2 weeks in some fetuses. After 24.5 weeks the angles were always acute (Figure 7e). DISCUSSION We have demonstrated that some cerebral sulci are readily visible at transabdominal ultrasound earlier than Ultrasound Obstet Gynecol 2004; 24: 706–715. Toi et al. 710 (a) (d) 15 20 25 30 Gestational age (weeks) Figure 4 Cingulate sulcus. (a) Optimal coronal plane of section through brain to show cingulate sulcus. (b) Ultrasound image of a 24.8-week fetus with an almost smooth medial hemispheric surface with only minimal dot-like irregularity, which is the earliest sign of sulcus formation (arrow). (c) Ultrasound image of a 30.3-week fetus showing appearance of cingulate sulci (arrows). csp, cavum septi pellucidi. (d) Graph illustrating the visibility of the cingulate sulcus in individual fetuses at different gestational ages. , visible; , not visible; , unable to assess. previously described. These include the parieto-occipital fissure and the calcarine, cingulate and some convexity sulci. It is important to understand how, when and where to look for early normal cerebral sulcal development. While sulci can be appreciated on multiple different views and projections, we have found that the views perpendicular to the expected course of the sulci are the most effective in detecting early sulcal development. It is important to remember that this technique demonstrates only part of a sulcus and helps establish its initial development. It does not mean that the entire sulcus and adjacent cortex are developing normally. There is correlation between anatomical, ultrasound and MRI studies of sulcal development (Table 1). However, the agreement is not perfect which is likely to be due to different definitions and opinions as to what constitutes the earliest manifestation of a sulcus. Further variation in assigning appearance times of sulci Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. could relate to the different techniques that have been used (for example, variations in thickness of slices in fetal neuropathological studies, use of photographs with differing lighting, and variations in orientation of serial sections of the brains). Also anatomical studies are only possible when normal pregnancy has been interrupted for various reasons and it is assumed that this has not affected cerebral maturation. In imaging studies, case numbers are generally small, the percentage with visible sulci is not always mentioned, and the earliest time of appearance of sulci is often not distinguished from the time of high percentage of visibility. Anatomical reports of sulcal appearance times differ by as much as 4–6 weeks4,5 . Generally, sulcal detection by imaging studies lags behind their anatomical appearance. The identification of the parieto-occipital fissure and calcarine sulcus by imaging lags behind anatomical identification by about 2 weeks (anatomy 16 weeks vs. Ultrasound Obstet Gynecol 2004; 24: 706–715. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. 507 10–44† 8–10 14 16 16 18 20 23 20–25 26 (22) (22) 24 24 28 24 24–26 24–26 24–26 25 12–38§ Lan et al.9 (2000) 80 22–41‡ Dorovini-Zis and Dolman5 (1977) 20 24 27 24 28 24 NA NA¶ Girard et al.6 (2001) 24.5–32 32–40 30–33 29–38 28–33 24.5–32 51 23–43** Ruoss et al.10 (2001) 173 22–38†† (22–23) (22–23) (22–23) 24–25 24–25 27 27 27 Garel et al.8 (2001) Magnetic resonance imaging 18–19 18–19 24–25 26–27 26–27 26–27 40 14–38‡‡ 14 Levine and Barnes7 (1999) 25–27 70 10–37§§ 12 21 25 25 26 Bernard et al.11 (1988) (14) 18 18 26 262 14–40¶¶ Monteagudo and Timor-Tritsch16 (1997) Ultrasound 23.2–27.9 18.5–20.5 18.5–21.9 23.2–24.3 50 15–29*** Present study (2004) The numbers in parentheses indicate the age range at which the sulcus was visible on the youngest brain available, although the sulcus was likely to have been identifiable earlier. *Any sulcus on outer convex hemispheric surface, generally central, postcentral or superior temporal sulcus. †Gestational age determined from last menstrual period (LMP) given by mother. Ages when named sulci were seen in 25–50% of brains. ‡Gestational age as given by mother and microscopic evaluation of fetal kidneys. Renal age derived from histology used in 11 cases with unknown or discrepant dates. §Gestational age estimated from LMP compensated by ultrasound crown–rump length measurement. ¶Gestational age determination technique not described. **Postpartum premature and term infant magnetic resonance imaging (MRI) study. Neonatal gestational age was calculated from LMP as well as early prenatal ultrasound. ††Age when sulci visible in over 75% of fetuses. Gestational age determined by 12-week ultrasound scan. ‡‡Gestational age based on LMP. All fetuses underwent an ultrasound scan on the same day as MRI and the ultrasound scan result correlated with menstrual age within 1 week. §§Gestational age determined from LMP and correlated with postnatal Dubowitz score and dating by ultrasound. ¶¶Patients included if they had known dates in agreement with ultrasound dates. ***Present study: 50 measurements in 46 fetuses at different gestational ages. Fetal age calculated from ultrasound biometry, which was in agreement with menstrual dates and/or first-trimester ultrasound scan. NA, not available. Fetuses (n) Age range (weeks) Interhemispheric sulcus Callosal sulcus Parieto-occipital fissure Calcarine sulcus Cingulate sulcus Central sulcus Superior temporal sulcus Convexity sulci* Chi et al.4 (1977) Anatomical Examination type/study Table 1 Age (menstrual weeks) when some cerebral sulci appear in normal fetuses at anatomical, magnetic resonance imaging and ultrasound examinations Normal fetal sulci 711 Ultrasound Obstet Gynecol 2004; 24: 706–715. Toi et al. 712 (a) B A (e) 15 Figure 5 Convexity sulci. (a) Optimal planes of section through a fetal brain to demonstrate lower (A) and higher (B) convexity cerebral sulci. (b) Ultrasound image of a 20.2-week fetus showing smooth surface of brain (arrow) before development of visible sulci (c) Ultrasound image of a 23.2-week fetus showing early appearance of a convexity sulcus (arrow) posterior to the Sylvian fossa (sf) imaged approximately along Plane A. (d) Ultrasound image of a 27.9-week fetus showing multiple unmistakable convexity sulci (arrows) imaged at about Plane B. (e) Graph illustrating the visibility of the convexity sulci in individual fetuses at different gestational ages. , definite; , probable; , not present. 20 25 30 Gestational age (weeks) ultrasound and MRI 18 weeks). The cingulate sulcus is more difficult to see and its appearance on ultrasound and MRI lags anatomical descriptions by about 7 weeks (anatomy 16 weeks vs. ultrasound 23 weeks and MRI 24 weeks). We believe that reported variations in identification of sulci will decrease as familiarity with the expected appearances increases. The insula/Sylvian fissure has a characteristic pattern of development. Anatomically, by 14 weeks, the Sylvian fossa becomes recognizable as a smooth lateral depression4,5 . By 18–22 weeks its edges become more Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. distinctly demarcated by the circular sulcus4,13,14 . These margins enclose a triangular plate-like area, which is the insula or island of Reil. The apex of the triangle is posterior and it widens and opens anteriorly. As the temporal and parietal lobes enlarge they overgrow the insula (operculization). Anatomically, operculization can be seen by about 22–24 weeks5,10,15 . It starts at the posterior pointed end of the insula and proceeds zip-like anteriorly5,16 . By 28–35 weeks, most of the insula is covered4,13,16 , but full closure of the most anterior part is not achieved until birth to 2 years14 . The insular plate remains smooth until insular sulci appear anatomically starting about 32–35 weeks4,14 at which time they can also be recognized on MRI7 . This pattern of development was also seen in the present study. As temporal and parietal operculization progressed, the angle between the insula and overgrowing brain changed from obtuse to Ultrasound Obstet Gynecol 2004; 24: 706–715. Normal fetal sulci 713 Figure 6 Echogenic appearance of calcarine sulcus in an older fetus when imaged by ultrasound in an axial plane parallel to its plane of orientation. (a) Coronal view at 27.7 weeks shows the calcarine sulcus (arrows). Note the ‘Y’ appearance characteristic of well-developed sulci in later pregnancy. The plane of the white arrows indicates the plane of the scan used in Figure 6b and 6c. (b) Axial view along the arrowed plane in Figure 6a shows an echogenic area (arrowheads) between the medial brain surface and ventricle (v). This is the normal appearance of the calcarine sulcus when it is imaged exactly along its plane. This should not be mistaken for brain abnormality. (c) Axial view just caudad to Figure 6b shows normal homogeneous hypoechoic white matter between medial brain surface (arrow) and ventricle (v) when imaging occurs just off the plane of the calcarine sulcus. acute. An acute angle could be seen in some fetuses by 23.2 weeks and in every fetus older than 24.5 weeks. The present study did not evaluate the effects of fetal gender, twinning and intrauterine growth restriction on sulcal development nor determine left–right symmetry of development. Fetal gender does not appear to affect sulcal development, with male and female brains developing similarly at anatomical, autopsy and neonatal cerebral ultrasound studies4,17,18 . There are, however, reports of variation in sulcal appearance time related to the other factors. Left–right symmetry of time of appearance of sulci is the rule in anatomical studies4,5,11,17 but a few exceptions are reported. Dorovini-Zis and Dolman evaluated symmetry in 23/80 brain samples and reported Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. that 5/23 showed left–right differences5 . In three cases the right superior temporal sulcus was evident earlier. In two cases the central sulcus appeared earlier, once on the right and once on the left. Chi et al. reported that the right superior frontal and superior temporal sulci, secondary sulci and right insular sulci were visible 1–2 weeks earlier than the left4 . In twins, Chi et al. found a delay of 2–3 weeks between 19 and 32 weeks but catch-up occurred by 33 weeks4 . Levine and Barnes studied six pairs of twins by MRI and found that some developed sulci at a similar rate to singletons but others lagged up to 3 weeks7 . Growth-restricted and small-for-gestational-age fetuses, and chronically stressed fetuses of mothers with chronic hypertension, can show accelerated functional and anatomical development. Hadi, in an autopsy study of 23 fetuses from 27 to 34 weeks’ gestation, found gyral maturation accelerated by 2 to 11 weeks in 19/23 fetuses in which growth restriction or maternal hypertension were present17 . Functional maturation also appears to occur earlier in such fetuses19 . Other factors should also be considered when evaluating sulcal development. With severe ventriculomegaly the brain may become so compressed that sulci may not be adequately visible and cannot be evaluated. Also Ultrasound Obstet Gynecol 2004; 24: 706–715. Toi et al. 714 (a) (e) 15 17 19 21 23 25 27 29 Gestational age (weeks) delays in sulcal development have been reported in association with other central nervous system abnormalities including holoprosencephaly, agenesis of corpus callosum, porencephaly, encephaloceles7,19 , microgyria, ischemia11 , tumors, encephalitis and severe intracranial hemorrhage14 . Thickening of sulci may be seen with subdural hematoma, external hydrocephaly, meningitis, toxoplasmosis and Sturge-Weber syndrome11 . It is important to remember that in the early second trimester the normal brain is still quite smooth and abnormal cortical development should not be diagnosed before 20 weeks of gestation. In addition, there is a spectrum of abnormal cortical development. Minor or focal lesions are Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. Figure 7 Insula and Sylvian fossa/fissure. (a) Optimal axial plane through brain to show insula and Sylvian fissure development and operculum formation. (b) Ultrasound image of a 17.8-week fetus showing smooth Sylvian fossa (arrow) without any angularity (arrowhead). The white line inferiorly shows the normal shape of the smooth Sylvian fossa in early pregnancy. (c) Ultrasound image of an 18.9-week fetus showing a plateau-like Sylvian fossa (arrow) with obtuse posterior angulation (arrowhead) at the site of the developing circular sulcus. (d) Ultrasound image of a 29.6-week fetus showing further development of the Sylvian fissure (arrow). The temporal operculum is overgrowing the insula and forms an acute angle posteriorly (arrowhead). (e) Graph illustrating the visibility of the insular angularity in individual fetuses at different gestational ages. , acute angle; , obtuse angle; , not angular; , unable to assess. likely to elude early prenatal detection by ultrasound at any age. Major abnormalities may be suspected by prenatal ultrasound. We have reviewed in a separate report our experience in the prenatal diagnosis of lissencephaly20 . In summary, we have described the ultrasound pattern of sulcal development in normal fetuses from 15 to 29 weeks’ gestation. We do not advocate a complete sulcal evaluation as part of the routine anatomical survey at 18–20 weeks. However, some cerebral sulci, especially the parieto-occipital fissure and calcarine sulcus, appear early and are usually readily visible when evaluating the occipital horns of the lateral ventricles. Knowledge of the sulcal development pattern is useful if there is suspicion Ultrasound Obstet Gynecol 2004; 24: 706–715. Normal fetal sulci of brain abnormality such as mild ventriculomegaly and in pregnancies with prior problems. We urge caution in the use of the present data as they are derived from a relatively small number of fetuses. A further study with a larger number of fetuses would help to confirm the discriminating gestational ages for the appearance of different sulci and help determine biological and interobserver variation. ACKNOWLEDGMENT The authors wish to thank Dr Sandeep Ghai for help with reference material. REFERENCES 1. Blaas HG, Eik-Nes SH, Kiserud T, van der Hagen CB, Smedvig E. Lissencephaly type I. 1992; http://TheFetus.net/[Accessed 26 May 2004]. 2. McGahan JP, Pilu G, Nyberg DA. Cerebral malformations. In Diagnostic Imaging of Fetal Anomalies, Nyberg DA, McHahan JP, Pretorius DH, Pilu G (eds). Lippincott Williams & Wilkins: Philadelphia, PA, 2003; 221–290. 3. Monteagudo A, Timor-Tritsch IE. Fetal neurosonography of congenital brain anomalies. 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