Advanced X-ray technology provides a viable pipeline for multiscale whole brain imaging

Researchers at the University of Chicago and the US Department of Energy’s (DOE) Argonne National Laboratory have used advanced X-ray microscopy techniques to close the gap between MRI (imaging resonance imaging) and electron microscopy imaging, which provides with a functional multiscale whole pipe thinking brain within the same brain.

Cognitive demonstration involving whole-minded mouse thinking in five order orders, which is a step that researchers say will better integrate existing ways of thinking and discover new details about brain structure.

The development, published June 9 in NeuroImage, will allow scientists to connect biomarkers to a much smaller scale, improve MRI imaging and provide greater electron microscopy.
The microscope uses a type of imaging called synchrotron-based X-ray tomography, which can be compared to a “micro-CT”, or a micro-computerized tomography scan. Thanks to powerful X-rays produced by the synchrotron particle accelerator at Argonne, researchers were able to mimic the entire brain of a mouse – about one cubic centimeter – in a micron, 1 / 10,000-centimeter solution. It took about six hours to collect images of all the brains, adding up to 2 terabytes (TB) of data. This is one of the quickest ways to complete brain thinking at this level of resolution.

MRI can quickly visualize the entire brain to trace neuronal pathways, but the solution is not enough to keep certain nerves or their connections. On the other side of the scale, electron microscopy (EM) can reveal details of individual synapses, but it creates a much larger amount of data, making it difficult to calculate pieces of brain tissue larger than a few micrometers per volume. Existing techniques for studying neuroanatomy in a micrometer solution are simply two-dimensional or use protocols that are not compatible with MRI or EM imaging, making it difficult to use the same brain tissue to think on all scales.

Researchers soon realized that their new micro-CT method, or µCT, could help close the existing gap. “There have been a lot of thought studies where people use MRI to look at the whole brain level and then try to confirm those results using EM, but there are exceptions to decisions,” said first author Sean Foxley, PhD, Research Assistant Professor at Chicago. “It’s hard to say anything about the huge volume of tissue you see with an MRI when you look at the EM database, and X-ray can close that gap. Now we finally have something that can allow us to look at all levels of resolution freely.”Combining their expertise in MRI and EM, Foxley, Kasthuri, and the rest of their team chose to make a single mouse brain map using these three methods. “Why did we choose the mouse brain? Because it goes through a microscope,” Kasthuri said with a laugh. “But also, the mouse is a neuroscience function; they are very useful in analyzing various experimental conditions in the brain. After collecting and storing the tissue, the team placed a sample on an MRI scanner to collect images of the entire brain structure. DOE Office of Science User Facility, to collect CT data before certain interesting regions are detected in the brainstem and EM cerebellum for identification.

After months of data analysis and image tracking, the researchers determined that they could use the generated MRI scanners to identify specific neuronal groups in selected brain regions, and that they could track the size and shape of each cell body. They can also track individual nerve axons as they travel to the brain, and are able to connect data from µCT images with what they see at the synaptic and EM level.

This approach, the team says, will not only help brain imagination in resolving µCT, but also in informing MRI and EM imaging.

“Imaging a 1-millimeter cube of the brain with EM, which is equivalent to the resolution of at least one MRI image, reveals about a million gigabytes of data,” Kasthuri said. “And that’s just looking at the 1 millimeter cube! I don’t know what’s going on in the next, or next cube, so I have no context for what I see with EM. MRI can provide the context without this size too big to block. needed for our EM work. ”On the other side of the scale, Foxley is excited about how this approach can help in understanding the living brain through MRI. “This approach gives us a very clear way to identify changes in the structure of the small brain where there is a disease or injury,” he said. “So now we can start looking for biomarkers with µCT that we can trace back to what we see on MRI in the living brain. X-ray allows us to look at things at the cellular level, so we can ask, what has changed at the cellular level that produced the MRI signal at the macroscopic level? ”

Researchers are already using this method to begin examining important questions in neuroscience, looking at genetically engineered mice to develop Alzheimer’s disease to see if they can get A? plaques detected by µCT return to measurable changes in MRI scans, especially in the early stages of the disease.

Importantly, because this work is being done in a national laboratory, this resource will be open and accessible to other scientists around the world, enabling researchers to begin asking and answering questions that affect the entire brain and reach a synaptic level.

At the moment, the Chicago team is very interested in continuing to improve the process. “The next step is to make the whole brain primate,” Kasthuri said. “The rat brain is possible, and it is useful in disease models. But what I really want to do is get the whole primate mind shown at the level of every neuron and all synaptic connections. And once we do that, I want to make the whole human brain.”The microscope uses a type of imaging called synchrotron-based X-ray tomography, which can be likened to a “micro-CT”, or micro-computerized tomography scan. Thanks to the powerful X-rays produced by the synchrotron particle accelerator at Argonne, the researchers were able to image the entire mouse brain — roughly one cubic centimeter — at the resolution of a micron, 1/10,000 of a centimeter. It took roughly six hours to collect images of the entire brain, adding up to around 2 terabytes (TB) of data. This is one of the fastest approaches for whole brain imaging at this level of resolution.

MRI can quickly image the whole brain to trace neuronal tracts, but the resolution isn’t sufficient to observe individual neurons or their connections. On the other end of the scale, electron microscopy (EM) can reveal the details of individual synapses, but generates an enormous amount of data, making it computationally challenging to look at pieces of brain tissue larger than a few micrometers in volume. Existing techniques for studying neuroanatomy at the micrometer resolution typically are either merely two-dimensional or use protocols that are incompatible with MRI or EM imaging, making it impossible to use the same brain tissue for imaging at all scales.

The researchers quickly realized that their new micro-CT, or µCT, approach could help bridge this existing resolution gap. “There have been a lot of imaging studies where people use MRI to look at the whole brain level and then try to validate those results using EM, but there’s a discontinuity in the resolutions,” said first author Sean Foxley, PhD, Research Assistant Professor at UChicago. “It’s hard to say anything about the large volume of tissue you see with an MRI when you’re looking at an EM dataset, and the X-ray can bridge that gap. Now we finally have something that can let us look across all levels of resolution seamlessly.”

Combining their expertise in MRI and EM, Foxley, Kasthuri, and the rest of their team opted to attempt mapping a single mouse brain using these three approaches. “Why did we choose the mouse brain? Because it fits in the microscope,” Kasthuri said with a laugh. “But also, the mouse is the workhorse of neuroscience; they’re very useful for analyzing different experimental conditions in the brain.”After collecting and storing the tissue, the team placed a sample on an MRI scanner to collect images of the entire brain structure. Next, it was placed in the exchange phase in the µCT scanner at Advanced Photon Source, DOE Office of Science User Facility, to collect CT data before certain interesting regions were detected in the brainstem and cerebellum to identify EM.

After months of data analysis and image tracking, the researchers determined that they could use the generated MRI scanners to identify specific neuronal groups in selected brain regions, and that they could track the size and shape of each cell body. They can also track individual nerve axons as they travel to the brain, and are able to connect data from µCT images with what they see at the synaptic and EM level.

This approach, the team says, will not only help brain imagination in resolving µCT, but also in informing MRI and EM imaging.

“Imaging a 1-millimeter cube of the brain with EM, which is equivalent to the resolution of at least one MRI image, reveals about a million gigabytes of data,” Kasthuri said. “And that’s just looking at the 1 millimeter cube! I don’t know what happens to the next cake, or the next, so I have no context for what I see with EM. MRI can provide some context unless that scale is too big to close. Now this µCT that’s the essence needed for our EM work. ”

On the other side of the scale, Foxley is excited about how this technique can help in understanding the living brain through MRI. “This approach gives us a very clear way to identify changes in the structure of the small brain where there is a disease or injury,” he said. “So now we can start looking for biomarkers with µCT that we can trace back to what we see on MRI in the living brain. X-rays allow us to look at things at the cellular level, so we can ask, what has changed in the cellular level that has produced global change in the MRI at the macroscopic level? Researchers are already using this method to begin examining important questions in neuroscience, looking at genetically engineered mice to improve Alzheimer’s disease to see if they can track A? Plaque detected by µCT and return to measurable changes in MRI scan, especially in the early stages of the disease.

Importantly, because this work is being done in a national laboratory, this resource will be open and accessible to other scientists around the world, enabling researchers to begin asking and answering questions that affect the entire brain and reach a synaptic level.

At the moment, the Chicago team is very interested in continuing to improve the process. “The next step is to make the whole brain primate,” Kasthuri said. “The rat brain is possible, and it is useful in disease models. But what I really want to do is get the whole primate mind shown at the level of every neuron and all synaptic connections. And once we do that, I want to make the whole human brain.”

Source:
University of Chicago Medical Center

Journal Reference:
Foxley, S., et al. (2021) Multi-path models of a single mouse brain more than five orders the size of a solution. NeuroImage. doi.org/10.1016/j.neuroimage.2021.118250. Posted to: Device / Technology News | Medical Science News | Medical Research Issues

Tags: Alzheimer’s Disease, Brain, Cell, CT, Electron, Electron Microscopy, Imaging, Laboratory, Magnetic Resonance Imaging, Micro, Microscope, Microscopy, Neuroanatomy, Neuron, Neurons, Neuroscience, Research, Stroke, Tomography, X-Ray, X- Ray Microscopy “

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