Cerebrospinal Fluid and Parenchymal Brain Development and Growth in the Healthy Fetus

Abstract

Objective: The objective of this study was to apply quantitative magnetic resonance imaging to characterize absolute cerebrospinal fluid (CSF) development, as well as its relative development to fetal brain parenchyma in the healthy human fetus.

Design: We created three-dimensional high-resolution reconstructions of the developing brain for healthy fetuses between 18 and 40 weeks' gestation, segmented the parenchymal and CSF spaces, and calculated the volumes for the lateral, third, and fourth ventricles; extra-axial CSF space; and the cerebrum, cerebellum, and brainstem. From these data, we constructed normograms of the resulting volumes according to gestational age and described the relative development of CSF to fetal brain parenchyma.

Results: Each CSF space demonstrated major increases in volumetric growth during the second half of gestation: third ventricle (23-fold), extra-axial CSF (11-fold), fourth ventricle (8-fold), and lateral ventricle (2-fold). Total CSF volume was related to total brain volume (p < 0.01), as was lateral ventricle to cerebral volume (p < 0.01); however, the fourth ventricle was not related to cerebellar or brainstem volume (p = 0.18-0.19).

Relevance: Abnormalities of the CSF spaces are the most common anomalies of neurologic development detected on fetal screening using neurosonography. Normative values of absolute CSF volume, as well as relative growth in comparison to intracranial parenchyma, provide valuable insight into normal fetal neurodevelopment. These data may provide important biomarkers of early deviations from normal growth, better distinguish between benign variants and early disease, and serve as reference standards for postnatal growth and development in the premature infant.

Keywords: Brain development; Fetus; Gender; Quantitative magnetic resonance imaging; Ventriculomegaly; cerebrospinal fluid.

Fig. 1.

Three-dimensional fetal brain reconstruction of a 31-week fetus. Extra-axial CSF noted in blue, lateral ventricles in pink, third ventricle in gray, fourth ventricle in brown with the surrounding parenchyma in shadows (color in online version only).

Fig. 2.

Total brain parenchymal volume (a), posterior fossa parenchymal volume (the combined brainstem and cerebellar volume) (b), and brainstem volume alone (c) between 18 and 40 weeks’ gestation. See online Supplementary Tables 1–3 (for all online suppl. material, see www.karger.com/doi/10.1159/000456711).

Fig. 3.

Extra-axial CSF volume (a), lateral ventricular volume (b), third ventricular volume (c), and fourth ventricular volume (d) between 18 and 40 weeks’ gestation. Lateral ventricular volume is presented separately for male fetuses (open circles and dashed lines) and female fetuses (crosses and solid lines) (see online suppl. Tables 4–8.)

Fig. 4.

Growth trajectories for the lateral ventricles by gender between 18 and 40 weeks; male fetuses are shown in a, female fetuses in b.

Fig. 5.

Relative changes of CSF volumes to surrounding parenchyma: total CSF volume in relation to total brain parenchyma (a), lateral ventricular volume in relation to cerebral volume (b), 4th ventricle in relation to posterior fossa parenchyma (c), and supratentorial volumes in relation to infratentorial volume (d).