The relative growth rates varied between structures with the cerebellum showing the fastest growth per week followed by the supratentorial brain tissue and the cortex, while the growth of the lateral ventricles was the slowest. The supratentorial brain tissue followed a quadratic growth pattern indicating accelerated growth at this stage of development as demonstrated by the increasing growth velocity in brain weight in the third trimester (Guihard-Costa and Larroche
1992). The absolute volume increased between 22 and 38 weeks at a relative growth rate of 13.04% per week. This is comparable with previous MR volumetric studies, performed on 3D reconstructed data within smaller gestational age ranges, which presented growth ranges of 10.22–17% (Clouchoux et al.
2011; Rajagopalan et al.
2011; Scott et al.
2011). The volume range increased from around 30 weeks of gestation suggesting that individual variation starts to arise and becomes greater with progressing age as previously shown (Guihard-Costa and Larroche
1992; Scott et al.
2011; Snijders and Nicolaides
1994). Cortical volume increased at a relative growth rate of 14.78% per week in our sub-cohort of fetuses. This is in agreement with a previous study performed on 34 normal fetuses at 20–31 gestational weeks (Scott et al.
2011). Cortical volume increased at a higher rate than the supratentorial brain tissue as demonstrated in the fetal (Scott et al.
2011) and preterm brain (Kapellou et al.
2006). Cortical volume was related to supratentorial brain tissue volume by a scaling exponent of 1.1. Our absolute cerebellar volumes are in agreement with earlier MR studies (Clouchoux et al.
2011; Grossman et al.
2006; Hatab et al.
2008; Limperopoulos et al.
2010). The relative growth rate of the cerebellum exceeded that of the supratentorial brain tissue as previously shown in post-mortem and MR studies (Clouchoux et al.
2011; Grossman et al.
2006; Hatab et al.
2008; Limperopoulos et al.
2010; Vatansever et al.
2013). The cerebellum exhibits an abrupt acceleration in growth velocity from 24 weeks of gestation in comparison with the supratentorial brain and maintains this acceleration until birth (Guihard-Costa and Larroche
1992; Moss and Noback
1956). Cerebellar volume related to supratentorial brain tissue volume by a scaling exponent of 1.25. The volume of the total lateral ventricles showed a moderate increase with increasing GA. This increase is minimal in comparison with brain growth. The existing MR volumetric studies have produced variable results as to whether the total volume of the lateral ventricles remains stable (Kazan-Tannus et al.
2007), increases (Scott et al.
2011) or decreases with GA (Clouchoux et al.
2011). This variability may be attributed to differences in the anatomical definition of the structure and inclusion of the third ventricle or the cavum septum pellucidum. We have previously shown in a sub-group (
n = 60) of this cohort that the volumes of the CSP, third and fourth ventricles, change significantly with GA (Kyriakopoulou et al.
2014). Extra-cerebral CSF volume increased at a relative growth rate of 9.6% per week from 22 to 38 weeks. The volume of the extra-cerebral CSF had a strong correlation with supratentorial brain growth from 22 to 30 weeks and a weak correlation thereafter. Extra-cerebral CSF volume related to supratentorial brain tissue volume by a scaling law exponent of 0.6. In contrast to all other brain structures, extra-cerebral CSF showed a deceleration in growth from around 30 weeks of gestation. This is in agreement to the visual observation of the MR images and the 2D measures of skull biparietal diameter—brain biparietal diameter. Ultrasound data from normal fetuses indicate a decrease in peri-cerebral spaces during gestation (Garel
2004). Unfortunately, it is not possible to compare with other MR volumetric studies as the CSF measures in these include all intracranial CSF spaces.
Similar to the evolution pattern of the extra-cerebral CSF volume, the 2D and 3D measures of the CSP also peak at 30 weeks (Kyriakopoulou et al.
2014), while amniotic fluid volume follows a similar bell-shaped trajectory peaking at around 30–32 weeks (Brace and Wolf
1989). In addition, our data on intracranial parameters indicate an increase in volume range in the supratentorial brain tissue, cerebellum, total lateral ventricles, and cortex around that time. It may be speculated that 30 weeks of gestation is a significant timepoint of fetal brain development with various intracranial structures exhibiting changes in their growth trajectories.
Correlation between 2D and 3D measurements
While all 2D measurements showed a strong positive correlation with increasing GA, neither the left nor right atrial diameter correlated with GA. Previous ultrasound studies have shown a significant but weak correlation with GA and the authors commented that this was not clinically significant (Almog et al.
2003; Hilpert et al.
1995). It is generally accepted in the literature that the ventricular atrium is relatively stable from 14 weeks of gestation until birth. Atrial diameter showed a moderate correlation with ventricle volume which we expected due to the complexity of the structure and variations that exist outside the posterior ventricular region. Similarly, extra-cerebral CSF had a moderate correlation with its respective 2D measurement (skull biparietal diameter–brain biparietal diameter) indicating that this linear measurement may not be sensitive enough to depict variation in extra-cerebral CSF volume. The extra-cerebral CSF linear measurement showed an increase from 22 to 30 weeks when it reached a peak and decreased from 30 to 38 weeks. Interestingly, this is a similar evolution pattern of the 2D and 3D measurements of the CSP (Kyriakopoulou et al.
2014). The 2D extra-cerebral CSF measurement will be predominantly affected by the development of the temporal lobes, while the 3D extra-cerebral CSF measurement will be affected by the development of all brain lobes. Therefore, we speculate that a difference in the trajectory of the 2D and 3D measures may be due to the differential growth rate of the brain lobes.
There was a strong correlation between head circumference and supratentorial brain tissue indicating that head circumference is an appropriate measure of brain size in appropriately developing fetuses. We measured the head circumference using two different methods as these are commonly used on antenatal ultrasound. Our data on head measurements are of great value for comparison with babies that have been born preterm and also with fetuses with a breech presentation as these are high-risk cohorts for developing biparietal head flattening.