Sonographic visualization and measurement of the fetal optic chiasm and optic tract and association with the cavum septum pellucidum

Introduction

The optic chiasm (OC) and optic tracts (OTs) are important components of the visual system and play a vital role in integrating and transmitting visual information from the retina to the brain [1]. The OC is an anatomical crossover; the OTs extending from the left and right eyes cross at the OC and directly to the brain’s opposite hemisphere [2]. The OC is an ‘X’ shaped area in the forebrain and is completely surrounded by the circle of Willis along with the pituitary stalk. The decussation of the OC is located at the center of the middle cerebral arteries, which arise laterally from the internal carotids [3]. Lesions affecting the optic chiasm can lead to varying degrees of visual field defects depending on the extent of the lesion [4]. Congenital lesion of the optic chiasm is mostly septo-optic dysplasia (SOD) [5].

Cavum septum pellucidum (CSP) is located in front of the thalamus and is one of the important parameters in the evaluation of the fetal brain. Sonographically, it appears in the transventricular section, between the anterior horns of the ventricles, in the midline, in a hypoechoic rectangular structure [6], 7]. An absent CSP is often indicative of midline fetal brain abnormalities. These anomalies frequently include holoprosencephaly, corpus callosum abnormalities, destructive brain lesions, obstructive hydrocephalus, and rarely SOD. Additional intracranial anomalies are often present in these anomalies, however the absence of CSP in SOD is an isolated finding [8], 9]. Therefore, evaluation of OC is necessary for the differential diagnosis of isolated absence of CSP.

The evaluation of OC and OT structures can be achieved by fetal magnetic resonance imaging (MRI), including skull base cross-section [10]. In recent years, developments in sonographic technologies and prenatal diagnosis techniques have paved the way for sonographic examination of these structures. However, studies evaluating the sonographic visualization of the OC during the prenatal period remain limited, with most focusing on cases involving the absence of the CSP [11], [12], [13], [14]. Therefore, although sonographic technologies have improved, OC visualization is still a challenge for clinicians and the diagnosis of SOD is often postponed until after delivery.

The aims of this study were to visualize and measure OC and OTs in fetuses with normal CSP and to examine the associations between OC, OT and CSP dimensions.

Materials and methods

This prospective cross-sectional study was conducted between February 2024 and June 2024 at the Maternal-Fetal Medicine Unit of a tertiary center in western Turkey. The study protocol received approval from the Izmir City Hospital Local Ethics Committee (Approval number: 2024/117). All participants were thoroughly informed about the study procedures, and written informed consent was obtained from each participant.

Participants were determined as pregnant women who underwent ultrasonographic fetal anomaly screening in the second trimester (19–23+6 weeks of gestation). Ultrasonographic fetal anomaly screening was performed according to the guidelines of the International Society of Obstetrics and Gynecology Ultrasound (ISUOG) published in 2022 [15]. Routine fetal anomaly screening was performed by transabdominal ultrasonography, and in pregnant women where the fetal position allowed optimal evaluation of intracranial structures, fetal OC and OT structures were also evaluated in addition to routine screening. Exclusion criteria for the study were fetal structural or chromosomal anomalies, obstetric and/or maternal medical comorbidities, and multiple pregnancies.

Each participant was examined once during the study period, and measurements were performed by two maternal-fetal medicine specialists (STC, CS) who are also gynecology and obstetrics experts with more than 10 years of obstetric ultrasonography experience. All measurements were performed three times for each participant and the averages were included in the analysis. The agreement between measurements of two operators was assessed using the intraclass correlation coefficient (ICC) after two consecutive sonographic evaluations. Intraobserver reproducibility was assessed in all participants and interobserver reproducibility was assessed in 30 participants. The optic chiasm width (ICC 0.881 95 % confidence interval (CI) [0.746; 0.971]), right optic tract width (ICC 0.826 95 % CI [0.716; 0.896]), and left optic tract width (ICC 0.803 [0.699; 0.871]) measurements demonstrated high intraobserver agreement levels. Also, optic chiasm width (ICC 0.783 95 % CI [0.688; 0.898]), right optic tract width (ICC 0.709 95 % CI [0.661; 0.858]), and left optic tract width (ICC 0.689 95 % CI [0.646; 0.831]) measurements demonstrated high interobserver agreement levels. Sonographic examinations and measurements were performed using the Voluson E8 expert machine (GE Healthcare, Austria) with a 2–9 MHz, 2D curvilinear transducer. All ultrasonographic examinations were performed transabdominally. The preset was set to second trimester obstetric setting. To best evaluate tissue changes, ultrasonic gain settings were adjusted individually for each fetus. CSP, OC and OT structures were examined in axial sections of the fetal head. The CSP was evaluated in the transventricular section and measurements were performed in frozen images after optimizing visualization. The widths of the CSP were performed from the anterior, middle, and posterior section by placing the cursor on the inner surfaces, and their averages were included in the analysis. The lengths of the CSP were measured from the inner edges in the anterior-posterior dimension (Figure 1). OC and OTs examinations were performed in accordance with the three-steps transabdominal fetal OC imaging guideline defined by Alonso et al. [16]. After obtaining the transverse image of the fetal brain in the transventricular section, frontal oblique sections were obtained by angling the probe caudally at 20–40° until the orbits were visualized. Color Doppler was activated for orientation, and the middle cerebral arteries arising laterally from the internal carotids and the circle of Willis were visualized. After the characteristic echogenic ‘X shape’ of the OC was identified, the Color Doppler was switched off and measured by placing the cursor on-to-on in the middle of the OC in the frozen image. OTs was visualized in the same section by angling the probe more caudally. Right and left OT widths were measured from their middle parts by placing the cursor on the borders (Figure 2).

Figure 1:

Width and length measurements of CSP (A, anterior; M, middle; P, posterior; L, length).

Figure 2:

Visualization and measurements of OC and OTs (MCA, middle cerebral artery; PCA, posterior cerebral artery; OC, optic chiasm; OT, optic tract).

Results

A total of 154 pregnant women were included in the study with the OC and OTs successfully visualized in 109 participants (70.8 %). Demographic, clinical and sonographic characteristics of the visualized and non-visualized OC and OTs groups are presented in Table 1. There was no significant difference between the two groups in terms of maternal age, parity, body mass index (BMI), and placental location (p>0.05, for all). The mean gestational week at measurement was significantly higher in the visualized group compared to the non-visualized group (21 ± 1.2 vs. 20.4 ± 1.1; p=0.007). Breech presentation was significantly more common in the visualized group compared to the non-visualized group (69.7 vs. 46.7 %; p=0.017).

The sonographic characteristics of the study participants are presented in Table 2. The mean OC width was 5.94 ± 0.6 mm, with the 5th percentile was 5.04 mm and the 95th percentile was 6.87 mm. For the right OT, the mean width was 1.82 ± 0.32 mm, with the 5th and 95th percentiles at 1.32 mm and 2.33 mm, respectively. The mean width of the left OT was 1.81 ± 0.29 mm, with the 5th percentile was 1.38 mm and the 95th percentile was 2.31 mm.

The mean, median, 5th percentile, and 95th percentile values of OC and OT measurements of fetuses at 19–23 weeks are presented in Table 3 for each gestational week. The mean OC width measurements were as follows: 5.59 ± 0.58 mm at the 19th week of gestation, 5.96 ± 0.53 mm at the 20th week of gestation, 5.84 ± 0.46 mm at the 21st week of gestation, 6.30 ± 0.69 mm at the 22nd week of gestation, and 6.23 ± 0.59 mm at the 23rd week of gestation. The mean right and left OT width measurements respectively were; 1.71 ± 0.28 mm and 1.63 ± 0.18 mm at the 19th week of gestation, 1.75 ± 0.33 mm and 1.79 ± 0.25 mm at the 20th week of gestation, 1.81 ± 0.32 mm and 1.84 ± 0.31 mm at the 21st week of gestation, 1.95 ± 0.2 mm and 1.89 ± 0.30 mm at the 22nd week of gestation, 2.07 ± 0.40 mm and 2.02 ± 0.30 at the 23rd week of gestation.

The correlations of OC and OTs widths with CSP length, CSP width, biparietal diameter (BPD), head circumference (HC), and gestational age at measurement are presented in Table 4. OC width was positively correlated with right and left OT width, CSP length and width, BPD, HC, and gestational age (p<0.05, for all). Right OT width was positively correlated with OC width, left OT width, CSP length and width, BPD, HC, and gestational age (p<0.05, for all). Left OT width was also positively correlated with OC width, right OT width, CSP length and width, BPD, HC, and gestational age (p<0.05, for all) (Figures 3–5).

Figure 3:

The correlation between OC and OT widths and right and left OTs.

Figure 4:

The correlations of OC and OT widths with CSP length.

Figure 5:

The correlations of OC and OT widths with CSP width.

Discussion

In this study, we examined the OC and OTs of 109 fetuses. Our findings showed that visualization success was 70.8 % in 19–23 weeks of gestation, and the success rate was higher in advanced gestational weeks and breech presentation. Our findings also showed that OC and OT widths were positively correlated with CSP length and width, BPD, HC, and gestational age.

The OC is formed by the crossing of the anterior optic nerves and the posterior OTs. This crossover begins to occur at 4–6 gestational weeks and then continues to develop with the optic nerves and OTs. It is located in the suprasellar cistern above the sella turcica, surrounded by the circle of Willis and plays a vital role in the visual pathway [1]. Developmental abnormalities of the optic disc and optic nerves are defined as SOD. In addition to visual findings in SOD, panhypopituitarism and psychomotor delay may also occur secondary to pituitary hypoplasia. Hypopituarism is present in 62–80 % of cases, and 30 % of all cases involve both visual and endocrine dysfunction. In these cases, visual symptoms lead to a poorer prognosis than endocrine findings alone [17], 18]. MRI allows the evaluation of septooptic structures in prenatal and postnatal life [19]. With the developments in sonographic technology and techniques, it has recently been reported that fetal OC and OT structures can be visualized by 3D and 2D sonography. Bault et al. examined the OT of 98 fetuses at 21–36 weeks of gestation with 3D sonography and found that the OT diameter increased linearly throughout gestation [14]. Viñals et al. also examined the OC widths of 115 normal fetuses at 21–30 weeks of gestation using 2D ultrasound in coronal section. They showed that OC measurements increased linearly with gestational age and that this measurement method provided good intraobserver repeatability and excellent interobserver reproducibility [11]. Recently, Wu et al. evaluated both OC and OT structures in sonographic axial sections involving 310 normal fetuses at 19–40 weeks of gestation. Their findings showed that OC and OT diameters increased linearly with gestational week, and interobserver and intraobserver reproducibility was excellent for OC but relatively low for OTs [20]. Although these studies confirm that OC and OT structures can be visualized sonographically during the prenatal period, they are limited in establishing comprehensive reference values for clinicians due to the small number of measurements at each gestational week. In this study, we examined the OC and OT structures using the transabdominal axial sections method recently reported by Alonso et al. [16]. Visualization of these structures was our primary aim in routine mid-trimester fetal anomaly screening. Our findings showed that the visualization success of OC and OTs was 70.8 % and that fetal breech presentation and advanced gestational age increased visualization. Our findings also showed that both OC and OT measurements had high intraobserver and interobserver reproducibility. Similar to previous studies, we found that OC and OT diameters were correlated with gestational age and were also positively correlated with BPD and HC measurements.

During the mid-trimester fetal anomaly ultrasound scan, the central nervous system is evaluated in three separate scanning plans, and one of the important milestones of the examination is the evaluation of the CSP [6]. It is located between two thin membranes separating the anterior horns of the lateral ventricles. Although its development begins earlier in fetal life, it is sonographically visible between 17 and 37 weeks of gestation [21], 22]. During the intrauterine period, the fetal brain continues to grow and differentiate. Fetal cortical structures and depths increase in accordance with gestational age and HC, and even a recent study by Mappa et al. showed that fetal gender is effective in this development [23], 24]. CSP measurements also show development in accordance with gestational age and HC, and in a recent study by Patelli et al. showed that fetal gender is also effective in CSP development [25]. Abnormal or absence CSP is associated with various midline brain anomalies such as holoprosencephaly, corpus callosum agenesis, schizencephaly, and acute brain pathologies. In these pathologies, additional central nervous system findings often contribute to the differential diagnosis [8], 26]. Since the absence of CSP in SOD is often an isolated finding, it is important to evaluate the development of OC and OT structures in these cases. The isolated absent CSP is often associated with normal postnatal development. In the study of Di Pasquo et al., which included 15 cases absent CSP, it was shown that 14 of the cases showed normal developmental findings in the postnatal follow-up and only one of the cases had SOD [27]. In their meta-analysis including 17 SOD cases, they reported that the absence of CSP was an isolated finding in 13 cases, and only mild or moderate ventriculomegaly was an additional finding in four cases [27]. The etiology of SOD remains unclear; disorders affecting prosencephalic development, including CSP, such as genetic defects, vascular disorders, and drug exposure, are the most important hypotheses [17], 28]. Although the association between SOD and the absence of CSP is well known, to our knowledge, there is no study yet examining the association between OC, OTs, and CSP development. In our study, we examined CSP lengths and widths along with OC and right-left OT diameters. Our findings showed a positive correlation between OC and OT diameters and CSP length and width measurements in the mid-trimester period.

This study has some limitations. Since only mid-trimester fetuses were examined, our findings do not reflect all gestational weeks. Performing ultrasonographic examinations only transabdominally may have increased the selection bias of fetuses in breech position. In addition, sonographic examination was performed only on healthy fetuses, visualization success may vary in fetuses with intracranial anomalies. This study also has its strengths. It was the largest-scale study including fetal OC and OT measurements in mid-trimester. Furthermore, to our knowledge, it is the first study to examine the association between OC and OT diameters and CSP dimensions.

In conclusion, the findings of this study demonstrate the feasibility of visualizing and evaluating fetal OC and OT structures during the mid-trimester. The OC and OTs were visualized transabdominally in axial sections with high intraobserver and interobserver reproducibility. In addition, OC and OT structures developed in correlation with gestational week as well as with BPD, HC, and CSP measurements.