The normal process of cerebral cortical development has been found to follow a predictable timetable throughout gestation.^1,2 Anatomic studies have demonstrated the increasing complexity of the fetal brain surface development in utero as gestational age advances.^3,4 Indeed, the pattern of development of fetal brain sulcation has been subjectively described by both magnetic resonance imaging and 2-dimensional (2D) neurosonography. However, developmental patterns described with the use of these imaging modalities generally lag two to four weeks when compared to anatomic studies.^5-9 For example, Lan et al⁶ reported the earliest visualization of the sylvian fissure by magnetic resonance imaging at 15 weeks, whereas Toi et al⁹ reported visualization of this structure for the first time by 2D ultrasonography at 15-16 weeks.

The sylvian fissure is the deepest lateral cerebral fissure, separating the temporal from the frontal lobes of the brain. Initially depicted as a smooth depression on the lateral surface of the brain hemisphere, the sylvian fissure can be identified in anatomic specimens by the third month of gestation.¹⁰ A recent study based on subjective evaluation of different cerebral fissures and sulci by 2D ultrasonography described the characteristic morphologic pattern of development of the sylvian fissure with increasing gestational age.⁹ This particular pattern of development of the sylvian fissure in fetuses without brain anomalies was characterized by: (1) a smooth margined indentation between 15 and 17 weeks; (2) the development of obtuse angular margins at the site of the developing circular sulcus between 17 and 20 weeks; and (3) a change from obtuse to acute angles after 24 weeks.

In a different study from the same group, Fong et al¹¹ retrospectively reviewed prenatal ultrasonographic examinations of 7 fetuses with lissencephaly associated with Miller-Dieker syndrome. By applying this specific pattern of sylvian fissure maturation, as well as the developmental patterns for other sulci described previously, the authors found that all cases of lissencephaly had delayed cortical development when compared with the normal brain development expected for the same gestational age. The sylvian fissure, in particular, was visualized in all fetuses after 20 weeks and found to consistently exhibit delayed maturation. The earliest diagnosis of lissencephaly was made at 23 weeks,¹¹ challenging previous ultrasound studies that reported the prenatal diagnosis of lissencephaly only at 27 to 28 weeks of gestation.^12,13

Because lissencephaly is associated with a wide spectrum of cerebral anomalies, and ultrasonographic analysis of fetal brain sulcation remains subjective in nature, only severe forms of lissencephaly can be detected by prenatal ultrasonography, whereas milder degrees of cerebral involvement (e.g. pachygyria) may be difficult to diagnose. This is particularly true for those fetuses examined before 20 weeks (around the time that a routine ultrasonographic examination is performed), in whom a subjective diagnosis of delayed cortical development may be impossible due to the normally smooth, shallow aspect of the sylvian fissure in the early second trimester.^9,11

The aims of this study were: (1) to develop an objective ultrasonographic parameter with which to assess the sylvian fissure throughout gestation; and (2) to determine the gestational age range for visualization of the sylvian fissure by 3-dimensional (3D) ultrasonography.

A total of 202 consecutive patients who met the eligibility criteria were included. Sylvian fissure identification and measurement were possible in 200 (99%) of the 202 patients from 12 to 41 weeks. The mean measurement ranged from 2.1 mm at 12 weeks to 14.3 mm at 41 weeks 5 days (Figures 2 and 3). Among the 2 patients in whom the sylvian fissure could not be identified, 1 was at 16 weeks 3 days and the other at 17 weeks 5 days. In both data sets, the resolution of the images was not sufficiently clear to identify the structure.

Figure 2 Multiplanar volume acquisition of the fetal head at 12 weeks 4 days of gestation depicting the transverse(A), coronal (B), and sagittal (C) planes with identification of the sylvian fissure (SF). D, Measurement of the SPB at 12 weeks of gestation.

Figure 3 Multiplanar volume acquisition of the fetal head at 36 weeks of gestation depicting the transverse(A), coronal (B), and sagittal (C) planes with identification of the sylvian fissure (SF). D, Measurement of the SPB at 36 weeks of gestation.

The mean intraobserver difference between measurements was 0.01 mm, with 95% limit of agreement ranging from -0.41 to 0.43 mm (Figure 4). The mean difference in measurements between observers was 0.05 mm, and the 95% limits of agreement were 1.79 to 1.90 mm (Figure 5).

Figure 4 Bland-Altman plot for intraobserver variation. The mean difference between measurements was 0.01 mm. The 95% limits of agreement ranged from -0.41 to 0.43 mm.

Figure 5 Bland-Altman plot for interobserver variation. The mean difference in measurements was 0.05 mm. The 95% limits of agreement ranged from -1.79 to 1.90mm.

Regression analysis of the SPB by gestational age was best described by a linear regression model: SPB = -2.85 + 0.43 × gestational age (R = 0.91; R² = 0.82) (Figure 6). The expected SPB values by gestational age are shown in Table 1.

Figure 6 Scatterplot of the measurements of the SPB. The bottom, middle, and top lines represent the 5th, 50th, and 95th percentiles, respectively.

Table 1 Expected SPB Values by Gestational Age (5th, 50th, and 95th Percentiles)

Improvements in ultrasound technology have increased the possibility of recognizing fetal brain structures with better resolution and at earlier gestational ages. Worthen et al¹⁵ initially assessed the relationship of cortical sulcal development with gestational age and proposed a grading system based on the complexity of structural development. This provided initial descriptive data showing the increase in general ultrasonographic sulcal complexity with gestational age, supporting prior anatomical findings,³ but not identifying specific structures. Bernard et al¹⁶ compared the ultrasonographic detection of intracranial structures in 70 fetuses ranging from 10 to 40 weeks with anatomic sections from 43 fetuses. Identification of the sylvian fissure was not noted until 21 weeks of gestation. In a retrospective trial of 337 transvaginal sonograms, Monteagudo and Timor-Tritsch⁸ evaluated the development of the fetal cortex with description of the gestational ages at which targeted sulci appeared. The sylvian fissure was consistently identified at 18 weeks of gestation. Toi et al⁹ prospectively examined 46 fetuses with targeted transabdominal neurosonography from 15.6 to 29.6 weeks of gestation. The sylvian fissure was identified in 1 fetus at 15 to 16 weeks of gestation and in all fetuses at 17 weeks of gestation in later. These studies, however, were all performed with 2D ultrasonography, in contrast to this study, which used 3D multiplanar imaging.

Applications of 3D ultrasonography continue to evolve as this technology becomes increasingly available in clinical practice. Among the potential benefits of 3D ultrasonography, the possibility of navigating the fetal brain in 3 orthogonal planes of a section has been proposed to facilitate the evaluation of the human fetal brain.^17;18 This observation has been endorsed by the recommendations of an American Institute of Ultrasound in Medicine concensus conference in 2005,¹⁹ which stated that although not the standard of care, 3D ultrasonography can be helpful in the evaluation of a variety of obstetric areas, including the fetal central nervous system. With 3D ultrasonography, the ability to correctly determine the multiple planes at which a landmark can be visualized also allows for standardization of measurement and evaluation.

There are few reports in the literature of comparison between 2D and 3D ultrasonographic visualization of the fetal brain. In a recent review of the clinical use of 3D/4D imaging in obstetrics, the authors describe 2 studies that directly compared 2D and 3D ultrasonographic examination of either normal or abnormal fetal brains.²⁰ Both studies demonstrated an increase in the accuracy of diagnosis and visualization of structures using 3D imaging.^21;22 Pilu et al²³ compared the use of 2D median planes and median planes reconstructed via 3D ultrasonography in the evaluation of midline structures in both normal and anomalous fetal brains. Three-dimensional median planes correlated well with 2D images, and 3D ultrasonography was noted to be a more rapid and easier method for obtaining median plane views. The ultrasonographic findings of both modalities correlated with anatomic findings. The authors, however, did note that in normal fetuses without brain anomalies, 2D views appeared to be of superior quality. A number of studies support the utility of 3D ultrasonography in central nervous system evaluation.^22;24-28 However, most of the literature involves obtaining 3D data sets via transvaginal ultrasonography. In a recent study, Correa et al²⁹ described the use of transabdominal 3D ultrasonography for fetal neurosonography. Fetal brain volume data sets of 202 prospectively enrolled patients from 16 to 24 weeks were evaluated for visualization of major cerebral anatomical structures, including various sulci. The investigators found that the use of volume datasets obtained transabdominally (as in the current study) is feasible for examination of the fetal brain. In fact, the sylvian fissure was visualized in 65% of fetuses at 16 to 17 weeks of gestation, which is similar to what has been reported previously. Our study included fetal sonograms from an earlier gestational age than in any previous studies. Using the described technique, we were able to visualize the sylvian fissure as early as 12 weeks of gestation.

In conclusion, this study demonstrates that: (1) the sylvian fissure can be identified from as early as 12 weeks of gestation with the use of 3D multiplanar ultrasonography; (2) the SPB can be reproducibly measured; and (3) it increases linearly with advancing gestational age. Because abnormal subjective assessment of sylvian fissure morphologic features is associated with neuronal migration disorders such as lissencephaly,¹¹ the SPB may prove to be a useful and objective parameter for identifying patients at risk for cortical dysmaturation, potentially at an earlier gestational age than previously described.

This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS.