Researchers from the Indian Institute of Technology-Madras have created a unique repository for neuroscientists — a cellular-level map of growing foetal brains.
To create this granular dataset, the researchers utilised the brains of five stillborn babies in the second trimester — a period when human brains grow rapidly in size and complexity. This helped scientists study how different brain structures grow and what leads to other neurological diseases.
What does the dataset tell us?
The researchers mapped the brains of babies that were stillborn at 4, 17, 21, 22, and 24 weeks of gestation. The dataset, called Dharini, currently has 5,132 plates of cross-sections of these brains available at granular, cellular resolution.
The researchers have essentially created a detailed 3D brain by putting these plates together. They have also been able to mark out 500 brain structures on it, thereby creating a map of the developing human brain.
The data of these five foetal brains are available for free to researchers, students, and others across the world. The researchers have also developed technologies and processes to quickly map the whole brain.
Currently, the centre has around 230 brains from its partner institutes, including the brains of neonates. The researchers are likely to expand their work and map the brains of children, young adults, and adults as well.
How did the researchers create the dataset?
To create the dataset, the researchers first took the brains of stillborn babies from partner hospitals. The brains were frozen in such a manner that there is minimal tissue damage and the structures within do not get affected. Once frozen, the brains are thinly sliced to a thickness of 10 to 20 microns, which is one-tenth or one-twentieth the thickness of one strand of human hair.
These thin cross-sections of the brain — which are transparent when thinly sliced — are stained and slides are prepared. The slides are microscopically imaged at a resolution of 1 to 0.5 microns — one-hundredth the thickness of a human hair. This information is then digitised and put together to create a 3D map of the brain.
The researchers from IIT Madras have developed their equipment and processes to carry out the work from start to finish. The researchers have developed a brain-freezing platform, an automated system to slice and transfer the tissue on glass slides, an automatic staining system, and a hands-free system to put the coverslip on the slides, and scanners that can capture whole slides at very high resolution among others. The researchers have also developed tools to view these microscopically scanned plates at very high resolution, a tool to visualise the brains in 3D, and another tool to annotate these plates at very high resolution and create a map.
“We are imaging whole human brains at scale — we are processing almost one large brain a month,” said Prof Mohanasankar Sivaprakasam, head of the Sudha Gopalakrishnan Brain Centre at the IIT-Madras.
How do such brain maps help?
The high-resolution images of the brains can help researchers understand how the brain works and what leads to different diseases. Looking at the developing brains can also give clues to what causes certain developmental disorders such as autism spectrum disorder. “This is path-breaking research for clinicians — it helps us understand the development of the human brain in the womb. It tells us when the foetuses develop various functions,” said Dr J Kumutha, Dean & Professor of Neonatology, at Saveetha Medical College and Hospital, the collaborating centre.
She added: “This data may also be able to tell us, for example, why some babies get permanent damage and cerebral palsy after a hypoxic episode (when oxygen supply is cut off) and why others do not. Studies in adult brains can also help understand what happens to the brain when a person has mental disorders such as depression, anxiety, bipolar disorder.”
There are several brain mapping initiatives ongoing across the world, which are aimed at helping researchers understand the structures of the brain and their functions, the different cell types, the connections within the brain, the electrical activity, as well as the expression of various genes.
Are there other such projects across the world?
Yes, there are several brain mapping initiatives across the world which have been studying the human brain using different techniques. The first complete brain atlas was that of a mouse brain released by the Allen Brain Institute in 2006. The same institute published its human brain atlas — which was an anatomically and genomically comprehensive 3D map — in 2016. It contained 1,356 plates of a female adult brain.
“Illustrations that depict the spatial arrangement of the structures of the brain have existed for at least five hundred years…But modern brain mapping is something else entirely, which goes beyond the simple image capturing and representation. The brain, unlike the surface of the planet, is a complex three-dimensional structure, whereas our practical means to represent and observe it remain two-dimensional,” said Dr Suzana Herculano-Houzel, editor in chief of the Journal of Comparative Neurology that will publish the IIT Madras atlas. It was also the journal that published the Allen Human Brain.
The US Brain Research through Advancing Innovative Neurotechnologies (BRAIN) is funding a constellation of mapping projects that can help understand brain function. European Human Brain Project was a decade-long research initiative for pioneering digital brain research. It contributed to a deeper understanding of the complex structure and function of the human brain with an interdisciplinary approach. Japan’s Brain/MINDS aims to understand human higher brain function, improve diagnosis and treatment of psychiatric and neurological disorders, and establish technologies based on brain mechanisms.
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