[extropy-chat] How to make a brain transparent

Keith Henson hkhenson at rogers.com
Fri Apr 6 22:19:04 UTC 2007

  Forwarded from an EP group.  Keith

  How to make a brain transparent
16:26 02 April 2007
NewScientist.com news service
Roxanne Khamsi

The new ultramicroscopy technique images a whole mouse brain in 3D
(Image: Hans-Ulrich Dodt et al./Nature Methods)
The entire neural network of a mouse's brain has been seen in 3D for the 
first time, using a new technique that renders tissues transparent.

The method - dubbed "ultramicroscopy" - has also enabled researchers to 
visualise the detailed anatomy of a mouse embryo in 3D. It will provide new 
insight into how organs such as the brain develop, the researchers say.

Until now, it has been impossible to visualise entire neuronal networks in 
an intact brain - techniques such as computer tomography (CT scans) or 
magnetic resonance imaging (MRI) do not have the resolution to reveal 
detail at the cellular level. Slicing the brain for microscopic imaging is 
possible, but creating a 3D image from many slices is laborious and prone 
to distortion problems.

Hans-Ulrich Dodt, now at Vienna University of Technology in Austria, and 
colleagues, have combined two old techniques to make a new tool that allows 
researchers to look at an entire brain on a microscopic level.

Take a look at a selection of images and video clips of the process here.

The new technique can also be used to image whole mouse embryos
(Image: Hans-Ulrich Dodt et al./Nature Methods)

Refractive index
Using rodents genetically engineered to produce florescent molecules in 
their nerve cells, the team extracted whole mouse brains and submerged them 
in alcohol to flush the water out of the tissues. The dehydrated brains 
were then placed into an oil mixture containing the solvents 
benzyl-benzoate and benzyl-alcohol.

Importantly, this medium has exactly the same light refractive index as 
protein - meaning that any light passing through the medium would continue 
to pass through the brain tissue at the same angle. Usually, when light 
enters a body tissue, it is scattered by the different refractive index of 
the tissue, in the same way that light is bent as it passes through water, 
making submerged items appear distorted.

The medium effectively made the organ transparent, much like a drop of oil 
on a piece of paper can make light pass more easily through the page, Dodt 

A whole mouse brain showing individual neurons fluorescing
(Image: Hans Ulrich Dodt)

Nerve connection
The next step involved viewing cross-sections of the brain by shining a 
thin sheet of light through the organ. As this sliver of light about six 
micrometres thick passed through the brain, it caused all of the neurons in 
its path to fluoresce. A computer then integrated the images obtained from 
scanning the thin sheet of light across the brain to give a 3D picture of 
how the nerves connect (see the results pictured, lower right)

Dodt claims the technique is a significant advance over previous methods to 
image the brain. Typically, approaches have involved physically cutting the 
brain into thin slices, and then staining the neurons in each slice. But 
the act of physically slicing the organ can distort the position of the 
nerves, he explains.

By comparing the scans of mouse embryos with those of adult mice they hope 
to get a better view on how mammalian brain networks change during 
development. This could give new insight into how mammalian brains change 
over time and what happens to information networks as a result of disease.

Journal reference: Nature Methods (DOI: 10.1038/nmeth1036)

Source: NewScientist

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