Digital Atlas Unveils Remarkable Insights Into Foetal Brain Maturation

In a recent study, a comprehensive digital atlas has provided insights into the intricate stages of human foetal brain maturation. This research sheds light on the structural organization and function of the developing foetal brain, ultimately offering a wealth of information that can impact long-term cognitive and developmental outcomes.

Traditionally, our understanding of foetal brain development has relied on postmortem data, which revealed a scheduled progression of cortical folding and growth, mainly beginning in the second trimester. Disruptions in these early processes can lead to significant malformations and functional impairments, as evidenced by Zika virus infections.

While Magnetic Resonance Imaging (MRI) studies have confirmed postmortem findings, they suffer from limitations such as small sample sizes and inconsistent methods. On the other hand, traditional two-dimensional ultrasound (2D US) provides valuable insights but lacks a comprehensive, large-scale mapping of foetal brain maturation.

To bridge this gap, the INTERGROWTH-21st Project embarked on a mission between 2009 and 2016. They collected three-dimensional ultrasound scans of foetal heads from eight global urban areas, involving only women with low-risk pregnancies who initiated antenatal care before the 14th week. 

A total of 899 healthy singletons were scanned, and their growth was compared to World Health Organization (WHO) standards. At the age of two, these children underwent a comprehensive neurodevelopment assessment using the globally recognized INTER-NDA tool.

The study meticulously curated high-quality ultrasound images, focusing on discernible brain structures. These images underwent alignment, brain extraction, and structural enhancement using convolutional neural networks and manual adjustments.

The result is a 4D atlas that intricately details fetal brain development across gestational ages. The study noted cerebral hemisphere asymmetry in fetuses, with most images showcasing the left hemisphere, in alignment with fetal positioning in utero. Only one cerebral area exhibited significant volume asymmetry between the hemispheres.

As foetal brains developed, increased variability between participants was observed. This research, conducted with the utmost ethical considerations, has made its results and tools available on GitHub. Volumetric ultrasound images from eight international study sites provided a comprehensive look at the fetal brain with submillimeter resolution.

The atlas offers a great level of detail in depicting cerebral lamination based on gestational age, rivalling what is seen in MRI images and histological sections. It highlights structures like the cortical plate and ventricular zone, among others.

While there are inherent differences between 3D ultrasound and MRI techniques, the striking similarities in tissue boundaries and shapes ensure the atlas's credibility.

Meticulous validation processes were employed to ensure the reliability of the collected image data. Variance component analysis and standardized mean site differences revealed only minimal variability attributed to site-based differences.

The study revealed that the healthy maturing brain exhibits dynamism, with particular periods of significant change occurring between 14 to 31 weeks. Notably, regions associated with language, such as the insular cortex, showed notable development during this window. Additionally, a detailed assessment across 34 cortical areas illustrated nuanced variability in their maturation trajectories.

Male and female foetuses did not show substantial discrepancies in brain structure up to the 31st week. This suggests that pronounced sexual characteristics in the brain have yet to manifest.

Another observation was the foetal brain's asymmetrical structure and growth rates. The left hemisphere's choroid plexus volume dominated from the 14th week onward, although this dominance waned as gestation progressed. Despite apparent bilateral symmetry, unique regional differences became evident at various developmental milestones.

In terms of overall brain growth, there was a substantial increase in total brain volume, closely correlating with established head circumference benchmarks. Furthermore, there were consistent growth rates between the brain's hemispheres.

To bolster the study's claims, brain scans initially excluded due to moderate quality were reviewed and aligned well with the primary data, further strengthening the study's findings.

In a two-year follow-up, most infants aligned well with WHO standards regarding growth, cognitive abilities, motor skills, and behaviour. Only a small fraction exhibited deviations in visual acuity and contrast sensitivity, reaffirming the study's reliability.