Technologies enable 3D imaging of whole human brain hemispheres at subcellular resolution
Observing anything and everything within the human brain, no matter how large or small while it is fully intact, has been an out-of-reach dream of neuroscience for decades, but in a new study in Science, an MIT-based team ...
"We performed holistic imaging of human brain tissues at multiple resolutions from single synapses to whole brain hemispheres and we have made that data available," said senior and corresponding author Kwanghun Chung, associate professor in The Picower Institute for Learning and Memory, the Departments of Chemical Engineering and Brain and Cognitive Sciences, and the Institute for Medical Engineering and Science at MIT.
"This technology pipeline really enables us to analyze the human brain at multiple scales. Potentially this pipeline can be used for fully mapping human brains."
The new study does not already present a comprehensive map or atlas of the entire brain, in which every cell, circuit and protein is identified and analyzed, but with full hemispheric imaging, it demonstrates an integrated suite of three technologies to enable that and other long-sought neuroscience investigations.
The research provides a "proof of concept" by showing numerous examples of what the pipeline makes possible, including sweeping landscapes of thousands of neurons within whole brain regions, diverse forests of cells each in individual detail, and tufts of subcellular structures nestled among extracellular molecules.
A section of human brain tissue (with two insets showing zoomed in areas), with 12 colors of labeling simultaneously resolving various cells, vasculature and proteins. Credit: Chung Lab/MIT Picower Institute
The imaging and analysis flow of the technology pipeline with sample images of rich labeling to distinguish large-scale brain structure (left), to circuits, to individual cells to individual synapses (right). Credit: Chung Lab/MIT Picower Institute
A comparison of what can be seen in the orbitofrontal cortex of control and Alzheimer's brain samples: Note in round 2 of labeling that much more amyloid beta (AB) is visible in the Alzheimer's sample (bottom row). The same is true for phosphyrlated Tau (pTau) in round 5. Credit: Chung Lab/MIT