The sphenoid bone is composed of paired cartilages. In the caudocranial direction, these are: hypophyseal cartilages, which form the larger posterior part of the sphenoid body; presphenoid cartilages, which form the anterior part of the sphenoid body; orbitosphenoid cartilages, from which the lesser wings of the sphenoid bone develop; alisphenoid cartilages, from which the greater wings of the sphenoid bone develop; as well as the lateral plate of the pterygoid process. The first endochondral ossification centers in the skull base appear in the 8th week of gestational age in the orbitosphenoid cartilages and in the 9th week of gestational age in the alisphenoid cartilages. This is followed by the occurrence of ossification centers in the hypophyseal cartilages at 11 weeks and in all other cartilages at 16 weeks of gestational age [2, 16].
As ossification progresses, most of the chondrocranium is replaced by bone, except the non-ossified synchondroses which have a temporary function of cartilaginous joints, existing between skull bones during the growth phase, and which eventually transform into bone tissue. Synchondroses play the role of growth centers, similarly to the epiphyseal plates of long bones. In human fetuses, within the sphenoethmoidal and spheno-occipital synchondroses, more bone tissue is deposited on the ethmoid and occipital bones than on the sphenoid bone, which applies to both the anterior (presphenoid) and posterior (basisphenoid) parts of the latter [2, 16].
In the presphenoid part, which forms the smaller part of the sphenoid body, two pairs of ossification centers are usually located – the lateral and middle ossification centers [12, 13, 15]. The lateral centers ossify before the middle centers. Some authors mention additional ossification centers, i.e. pairs of the anterior and posterior accessory centers, and the single middle, accessory center. The progressing fusion of the ossification centers of the presphenoid part of the sphenoid body forms a triangular area called the olivary eminence or the anterior foramen. This eminence usually disappears around the time of birth, and the foramen is so small that it should not be mistaken for a sinus or encephalocele [15].
In a study by Kodama [7], it was shown that the lateral ossification centers appear first. The centers were observed in 9.09 ± 8.67% of fetuses of 180 mm in length, in 86.66 ± 13.33% of fetuses measuring 290–315 mm, and in all fetuses larger than 320 mm in length. Subsequently, the anterior accessory centers were observed in 9.09 ± 8.67% of 245 mm-long fetuses, in 46.66 ± 12.88% of those measuring 290–315 mm, and in 100% of fetuses from the 9th month of gestational age. The posterior accessory center appeared in only 13.33 ± 9.35% of fetuses of 310 mm in length. The middle accessory center was observed in 8.33 ± 8.47% of fetuses measuring 340 mm, and in 30.00 ± 14.49% of those at 9 months of gestational age. The author hypothesized that the posterior and middle accessory ossification centers do not appear in the prenatal period. The middle accessory center was noted in 50.00 ± 14.43% of fetuses of 320–400 mm in length, and in all fetuses from 9 months of gestational age.
The boundary separating the presphenoid and basisphenoid parts of the sphenoid body is the tuberculum sellae. The synchondrosis between these two parts ossifies shortly before birth [9]. In the basisphenoid part, which forms the greater part of the sphenoid body, there are four ossification centers: two medial and two lateral [12–15]. The medial ossification centers can form one larger center on the midline, and such variations explain the different periods for the closing of the craniopharyngeal duct, which remains patent in 0.4% of the skulls of neonates during the postnatal period and constitutes the basis for the development of craniopharyngioma. Ossification of the basisphenoid part leads to the formation of the sella turcica and the dorsum sellae [9, 15].
Kodama [7] observed that the lateral/main centers of the presphenoid part begin to fuse with the basisphenoid centers in fetuses of 315 mm in length, and appear fused in all studied fetuses as late as from 9 months of gestational age. At the same time, the middle accessory centers of the presphenoid part begin to fuse, and complete fusion can be observed in all fetuses from the 9th month of gestational age.
Zhang et al. [21] observed two ossification patterns of the basisphenoid part. In the first pattern, the medial ossification centers fused at an early stage of development (CRL 120–140), and in the second pattern, the centers remained separated for a longer period and fused at a later stage (CRL 170). The authors also measured the distance between the two most distant points of the basisphenoid ossification center which, on average, was 3.35 ± 0.58 mm (CRL 120), 4.72 ± 0.48 mm (CRL 130), 4.41 ± 0.65 mm (CRL 140) and 4.47 ± 0.69 mm (CRL 170). For a single ossification center, the mean distance was 3.72 ± 0.58 mm, and for a double ossification center, the mean distance was 4.83 ± 0.45 mm.
The two ontogenetically separate parts of the sphenoid body, presphenoid and basisphenoid, separated by the sella turcica, have different origins and growth rates. From an evolutionary point of view, the posterior part of the skull base has retained the structures present in early mammals, while the anterior part is considered as an evolutionarily new region with a great effect on the development of the viscerocranium, characteristic of humans [18]. Scott [17] stressed the key importance of the sphenoid bone, whose variations are responsible for the variability of the skull base shapes. Lieberman [11] claimed that the shortening of the sphenoid body in a sagittal dimension may alter the spatial relationship between the skull base, the viscerocranium and the cranial roof, and may determine the protrusion of the viscerocranium. The sphenoid bone is an important structure for the morphogenesis of the skull base, and developmental defects of the sphenoid region can be observed in many congenital facial deformities, including craniosynostosis, cleft lip and cleft palate, and Down syndrome [18].
Utsunomiya et al. [18] observed a small but interesting difference between the morphogenesis of the presphenoid and basisphenoid parts of the sphenoid body, where the shape change in the presphenoid part took longer than in the basisphenoid part of the sphenoid body. The authors suggested that the presphenoid part may be more plastic and undergoes a stronger reconstruction. Consequently, the above seems to confirm the hypothesis that during evolution, the presphenoid part had the potential to create specific features of the human face through such plasticity and instability. In addition, in patients with congenital abnormalities of the viscerocranium, it is suggested that the skull base deformations are likely to be more common in the presphenoid part, including the sphenoid and ethmoid region, than in the basisphenoid part.
Utsunomiya et al. [18], in a study employing PCX-KT, measured the distance between the basisphenoid part and the sella turcica in 57 fetuses. The distance was measured in fetuses from 19 weeks of gestational age and was: 2.33 ± 0.18 mm for 19 weeks, 2.65 ± 0.06 mm for 20 weeks, 2.82 ± 0.22 mm for 21 weeks, 3.05 ± 0.26 mm for 22 weeks and 3.60 ± 0.31 mm for 23 weeks of gestational age. The distances were measured in the sagittal plane.
Mehemed et al. [13] studied 32 fetuses at 12 to 31 weeks of gestational age using MRI. The study was conducted to assess the applicability of MRI in the observation of ossification centers, e.g. in the hypophyseal cartilages. The authors observed the centers in 84% of cases, demonstrating their growth in accordance with gestational age (R2 = 0.307).
This paper is the first literature report of a morphometric analysis of the sphenoid body ossification centers in human fetuses using CT and, concurrently, mathematical models describing their growth. In the analyzed range of gestational age, two main ossification centers were observed in both the presphenoid and the basisphenoid parts.
The dimensions of the ossification center of the presphenoid part of the sphenoid body followed the functions: \(y=0.680+0.312 \times \text{a}\text{g}\text{e} \pm 0.007\)for the sagittal diameter, \(y= - 5.069+2.492 \times \text{ln}\left(age\right) \pm 0.064\) for the transverse diameter, \(y=- 5.414+0.612 \times \text{a}\text{g}\text{e} \pm 0.288\) for projection surface area, and \(y=- 17.409+1.741 \times \text{a}\text{g}\text{e} \pm 1.107\)for volume. The dimensions of the ossification center of the basisphenoid part of the sphenoid body followed the functions: \(y= -5.149+2.567 \times \text{ln}\left(age\right) \pm 0.082\) for the sagittal diameter, \(y=-5.382+2.924 \times \text{ln}\left(age\right) \pm 0.068\) for the transverse diameter, \(y= -29.434+12.629 \times \text{ln}\left(age\right) \pm 0.340\) for projection surface area, and \(y=-18.078+1.873 \times \text{a}\text{g}\text{e} \pm 1.279\) for volume.
In our earlier study of the development of the ossification centers of the lateral and basilar parts of the occipital bone, their growth dynamics followed linear functions of gestational age: \(y= -3.714+0.681 \times \text{a}\text{g}\text{e} \pm 1.346\)for the sagittal diameter of the lateral parts, \(y=0.412+0.278 \times \text{a}\text{g}\text{e} \pm 0.269\)for the transverse diameter of the lateral parts, \(y= -71.467+5.403 \times \text{a}\text{g}\text{e} \pm 7.500\)for the projection surface area of the lateral parts, \(y= -88.858+6.655 \times \text{a}\text{g}\text{e} \pm 9.767\)for the volume of the lateral parts, \(y=3.423+0.140 \times \text{a}\text{g}\text{e} \pm 0.157\)for the sagittal diameter of the basilar part, \(y=2.686+0.142 \times \text{a}\text{g}\text{e} \pm 0.159\)for the transverse diameter of the basilar part, \(y= -0.893+1.391 \times \text{a}\text{g}\text{e} \pm 1.385\)for the projection surface area of the basilar part, \(y= -1.517+1.827 \times \text{a}\text{g}\text{e} \pm 1.859\)R2 = 0.93 for the volume of the basilar part [6].
Levaillanto and Mabille [10] compared the images of the sphenoid bone in fetuses acquired by 3D ultrasound and CT and found that the images obtained using both techniques were very similar. Therefore, results obtained from the morphometric measurements of ossification centers using CT may allow more accurate diagnostics of developmental disorders and may enable further research of developmental processes and biometric associations.
In medical literature, there are no reports concerning the dimensions of the sphenoid body ossification centers in human fetuses, which precludes a more comprehensive discussion on this topic.
The main limitation of this study was a relatively narrow gestational age group, ranging from 18 to 30 weeks, and a small number of cases, including 37 human fetuses.