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Ten years ago, Dr. D., a professor of molecular and cellular biology at Harvard University. Jeff Lichtman took a small brain sample in his laboratory.
1 cubic millimeter of tissue, although small, was large enough to contain 57,000 cells, 230 millimeters of blood vessels and 150 million synapses.
“It was smaller than a grain of rice, but we started cutting it open and looking at it, and it was really beautiful,” he said. “But as I accumulated data, I realized we had way more ways than we could handle.”
Ultimately, Lichtman and his team extracted 1,400 terabytes of data from the sample; This roughly corresponds to the content of more than 1 billion books. After a decade of close collaboration by the lab team with scientists at Google, these data turned into the most detailed map of a human brain sample ever created.
300 million images
The brain sample came from a patient with severe epilepsy. Lichtman said it’s standard procedure to remove a small section of the brain to stop seizures and then look at the tissue to make sure it’s normal. “But it was anonymized, so I knew almost nothing about the patient other than his age and gender,” he said.
To analyze the sample, Lichtman and his team first cut it into thin sections using a sharp-edged blade made of diamond. The sections were then embedded in a hard resin and sliced again very thinly. “It’s about 30 nanometers, or roughly 1/1000th the thickness of a human hair. “They would be almost invisible if we didn’t dye them with heavy metals, making them visible when doing electron imaging,” he said.
The team ended up with several thousand slices that were collected with custom-made tape, creating a kind of filmstrip: “If you take pictures of each of these sections and align those pictures, you get a three-dimensional piece.” “Microscopic view of the brain.”
That’s when the researchers realized they needed help with the data because the resulting images would take up a significant amount of storage space.
Lichtman knew that Google was working on a digital map of a fruit fly’s brain released in 2019 and had the right computer hardware for the job. He contacted Viren Jain, a senior staff research scientist at Google who was working on the fruit fly project.
“There were 300 million individual images in Harvard’s data,” Jain said. “What makes this so much data is that you’re imaging at a very high resolution, at the level of an individual synapse. And there were 150 million synapses in just this small sample of brain tissue.”
Scientists at Google used AI-based processing and analysis to make sense of the images, determining what types of cells were in each image and how they were connected. The result is an interactive 3D model of brain tissue and the largest dataset ever built at this resolution of human brain structure. Google made it available online as “Neuroglacer,” and a study co-authored by Lichtman and Jain was also published in the journal Science.
understanding the brain
The collaboration between the Harvard and Google teams resulted in color images that make individual components more visible, but otherwise represent the texture faithfully.
“The colors are completely arbitrary,” Jain explained, “but beyond that there’s not a lot of artistic license here. The whole point is that we’re not making this up; these are real neurons, real wiring that exists in the brain, and we’re actually making it available and available for biologists to see and study.” We make it accessible.”
The data contained some surprises. For example, instead of forming a single connection, pairs of neurons number more than 50. “It’s like two houses on a block having 50 separate phone lines connecting them. What’s going on there? Why are they so strongly connected? We don’t know yet what the function or significance of this phenomenon is, we’ll need to investigate further,” he said.
Eventually observing the brain at this level of detail could help researchers understand unsolved medical conditions, according to Lichtman.
“What does it mean to understand our brain? The best we can do is to describe it, and we hope that from these descriptions will emerge an awareness of how normal brains differ from impaired brains, for example, in adult psychiatric illnesses or developmental disorders such as the autism spectrum. “This kind of comparison would be very valuable,” he said. “It will eventually give us an idea of what’s wrong, and in many cases we still don’t know about it.”
Lichtman also believes that the data set may be full of other surprising details that have not yet been discovered due to its size: “And that’s why we’re sharing it online, so anyone can look at it and find something.” Additional.
The team behind the project then aims to create a complete map of a mouse brain, which would require 500 to 1,000 times as much data as a human brain sample.
“That means 1 exabyte is 1,000 petabytes,” Lichtman said. “A lot of people are thinking hard about how we do this, and we’re in the first year of a five-year proof of principle process. I think having a complete wiring diagram of the mammalian brain would be a breakthrough for neuroscience; It would answer many questions. And of course, it would bring up a lot of problems, things we didn’t expect.”
But what about mapping the entire human brain? Lichtman explained that it will be 1000 times larger, which means the data will be 1 zettabyte. According to Cisco, this was the size of all internet traffic in 2016. Not only would it be difficult to even store that much data right now, there would also be no ethically acceptable way to obtain an intact, well-preserved human brain, Lichtman said.
We are breaking new ground
Researchers in the same field who were not involved in the study expressed excitement when contacted by CNN for comment.
“This study is amazing, and there is a lot to learn from data like this,” said Michael Bienkowski, an assistant professor of physiology and neuroscience at the University of Southern California Keck School of Medicine.
“Most of what we think we understand about the human brain has been derived from animals, but studies like this are critical to uncovering what makes us truly human,” Bienkowski said. Visualizing neurons and other brain cells is really challenging because of their density and complexity, and the existing dataset is more “It cannot capture long-range connections,” he said.
“From what other parts of the brain do these inputs come and where do the outputs go after they leave the area? “But seeing all these different cell types and their interactions is incredible and makes you appreciate what a masterpiece of architectural life has to offer us,” he added.
Andreas Tolias, professor of ophthalmology at Stanford University in California, agrees. “This is an extraordinary technical work that reconstructs the structure of the human cortex at high resolution,” he said. “I was particularly excited by the discovery of rare axons that can form up to 50 synapses. This finding is intriguing and raises important questions about their computational role.”
According to neuroscientist Olaf Sporns, the brain mapping project opens the door to future research.
“Each human brain is a vast network of billions of neurons,” said Sporns, distinguished professor of psychology and brain sciences at Indiana University. “This network allows cells to communicate in very specific patterns that are fundamental to memory, thought and behavior. Mapping this network, the human connectome, is critical to understanding how the brain works,” he added, adding that the work breaks new ground toward this important goal. that it opens up and offers exciting new opportunities for exploration and discovery.
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