Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment

Abstract

Down Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify the development of the fetal and neonatal brain in DS participants, with and without a congenital cardiac defect compared with a control population using dedicated, optimised and motion-corrected in vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks' gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, we believe that the results of this study will assist counselling for prospective parents.

Keywords: Brain; Down Syndrome; Fetal; MRI; Neonatal.

Fig. 1

Visual representation of linear measurements in the fetal brain in the axial plane (a: BPD–brain, (b): BPD–skull, (c): OFD–brain, (d): OFD–skull, (e): cavum width, (f): HC, (g): TCD; (h): vermis height; (i): vermis width; (j): vermis surface area).

Fig. 2

Volumetric segmentation of the fetal brain. Segmentation of T2-weighted volumetric MR images in the axial, sagittal and coronal planes showing (a) supratentorial brain tissue (red), (b) cortex (green), (c) lateral ventricles (dark blue), (d) extra cerebral cerebrospinal fluid (light blue); and (e) cerebellar hemispheres (pink), cerebellar vermis (bright green), pons (yellow) and fourth ventricle (blue).

Fig. 3

Volumetric segmentation of the neonatal brain. (a) Reconstructed T2 neonatal brain, (b) automatic neonatal brain segmentation; supratentorial brain tissue (bright blue + green + gray), cortex (green), lateral ventricles (light blue), extra cerebral cerebrospinal fluid (red), cerebellar hemispheres (pink); and brainstem (deep blue).

Fig. 4

2D and 3D regional measures of the brain in fetuses and neonates with DS and a congenital heart defect (DS + CHD; red circles), DS without a congenital heart defect (DS–CHD; Blue squares), and age-matched normal controls (black triangles). (a) Whole brain volumes, (b) Cortical volumes, (c) Biparietal diameter (BPD)–skull, (d) Biparietal diameter (BPD)–brain, (e) Occipitofrontal diameter (OFD)–skull, (f) Occipitofrontal diameter (OFD)–brain, and (g) Head circumference (HC) (MRI derived).

Fig. 5

2D and 3D measures of the cerebellum in fetuses and neonates with DS and a congenital heart defect (DS+CHD; red circles), DS without a congenital heart defect (DS–CHD; blue squares), and age-matched normal controls (black triangles). (a) Cerebellar volume, (b) Transcerebellar diameter, (c) Vermis height (d) Vermis width, and (e) Vermis surface area.

Fig. 6

2D and 3D measures of the CSF regions in fetuses and neonates with DS and a congenital heart defect (DS + CHD; red circles), DS without a congenital heart defect (DS – CHD; blue squares), and age-matched normal controls (black triangles). (a) Lateral ventricular volume, (b) eCSF volume, and (c) Cavum width.