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How do we study brains?

As far as we know, there’s only one thing in our solar system sophisticated enough to study itself: the human brain. But this self-investigation is challenging because a living brain is shielded by skull, swaddled in tissue, and made up of billions of tiny cells. How do we study living brains without harming their owners.

Year 2015: EXPANSION MICROSCOPY

MIT researchers led by Ed Boyden have invented a new way to visualize the nanoscale structure of the brain and other tissues. Unlike traditional microscopy, which involves magnifying the image, the new method works by physically enlarging the specimen itself, in some cases more than five times in each dimension.

A polymer: 
The prefix “poly” means many. A  polymer is a long chain of molecules made up of many smaller units, called monomers.

In this case
the super-absorbent polymer Prof. Ed Boyden & Prof. Paul Tillberg & Research Assistant Fei chen are talking about is .. Sodium Polyacrylate - sodium salt of polyacrylic acid.  (It is  found in insta-snow too!)

Picture

3 of 6 : The Process:

The process of enlargement begins by embedding a biological specimen inside a gel solution of densely crosslinked electrolytes, then mechanically homogenizing the cell. Next, the gel is expanded, thus also expanding the organism, by a fold linear expansion.

This process is essential as it provides an anchor for the key biomolecules within the cell (e.g. organelles, cytoskeleton, etc). By using this method of microscopy, scientists are more able to observe smaller cellular structures, as well as possibly observe more biomolecular structures which may not have ben as easily observed with just light microscopy alone.

LATTICE LIGHT SHEET MICROSCOPY:

First developed by Nobel Laureate Dr. Eric Betzig, the Lattice LightSheet microscope is capable of imaging biological systems spanning four orders of magnitude in space and time. The system generates an optical lattice to create an ultra-thin light sheet to image biological samples over long periods of time and with very fine resolution. This allows for 4D living cell imaging, where experiments limited to seconds or minutes on other imaging platforms can be extended to hours or even days. The combination of high spatiotemporal resolution, imaging speed and sensitivity make Lattice LightSheet the ultimate imaging tool for a new era of living cell microscopy.



COMBINING EXPANSION MICROSCOPY & LATTICE LIGHT-SHEET MICTOSCOPY:

Researchers have developed a new way to image the brain with unprecedented resolution and speed. Using this approach, they can locate individual neurons, trace connections between them, and visualize organelles inside neurons, over large volumes of brain tissue.

The new technology combines a method for expanding brain tissue, making it possible to image at higher resolution, with a rapid 3-D microscopy technique known as lattice light-sheet microscopy. In a paper appearing in Science Jan. 17, the researchers showed that they could use these techniques to image the entire fruit fly brain, as well as large sections of the mouse brain, much faster than has previously been possible. The team includes researchers from MIT, the University of California at Berkeley, the Howard Hughes Medical Institute, and Harvard Medical School/Boston Children’s Hospital.

google's AI maps fruit fly brains:
​

Google’s latest research dives deep into the brains of fruit flies — quite literally. In collaboration with the Howard Hughes Medical Institute (HHMI) Janelia Research Campus and Cambridge University, the tech giant today published the results of a study (“Automated Reconstruction of a Serial-Section EM Drosophila Brain with Flood-Filling Networks and Local Realignment“) that explores the automated reconstruction of an entire fly’s brian neuron by neuron.

 In the spirit of open source, they’ve made the full results available for download and browsable online using Neuroglancer, an in-house interactive 3D interface.

1 of 6: How do brain scans work


2 of 6: the invention of expansion microscopy


3 of 6: expansion microscopy


4 of 6: Lattice light sheet microscopy


5  of 6:  reconstruction of Drosophila neurons


A new fly-through of the fly brain


GOOGLE'S AI MAPS FRUIT FLY BRAINS:

The team behind the success of this image processing behemoth have released their work in the form of an interactive platform Neuroglancer. It is an open-source project that enables viewing of petabyte-scale 3D volumes, and supports many advanced features such as arbitrary-axis cross-sectional reslicing, multi-resolution meshes, and the powerful ability to develop custom analysis workflows via integration with Python. 

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