[ExI] Making brains transparent for HD brain imaging
avant at sollegro.com
Sun Mar 24 18:11:27 UTC 2019
I just happened upon this Nature article from 2013 that blew me away
and certainly has implications for cryonics and uploading. The highly
recommended video shows off an incredible new brain imaging technique
called CLARITY that uses detergents and a hydrogel to make entire
brains transparent to light microscopes, allowing unprecedentedly
detailed connectome mappings:
A chemical treatment that turns whole organs transparent offers a big
boost to the field of ‘connectomics’ — the push to map the brain’s
fiendishly complicated wiring. Scientists could use the technique to
view large networks of neurons with unprecedented ease and accuracy.
The technology also opens up new research avenues for old brains that
were saved from patients and healthy donors.
“This is probably one of the most important advances for doing
neuroanatomy in decades,” says Thomas Insel, director of the US
National Institute of Mental Health in Bethesda, Maryland, which
funded part of the work. Existing technology allows scientists to see
neurons and their connections in microscopic detail — but only across
tiny slivers of tissue. Researchers must reconstruct three-dimensional
data from images of these thin slices. Aligning hundreds or even
thousands of these snapshots to map long-range projections of nerve
cells is laborious and error-prone, rendering fine-grain analysis of
whole brains practically impossible.
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The new method instead allows researchers to see directly into
optically transparent whole brains or thick blocks of brain tissue.
Called CLARITY, it was devised by Karl Deisseroth and his team at
Stanford University in California. “You can get right down to the fine
structure of the system while not losing the big picture,” says
Deisseroth, who adds that his group is in the process of rendering an
entire human brain transparent.
The technique, published online in Nature on 10 April, turns the brain
transparent using the detergent SDS, which strips away lipids that
normally block the passage of light (K. Chung et al. Nature
http://dx.doi.org/10.1038/nature12107; 2013). Other groups have tried
to clarify brains in the past, but many lipid-extraction techniques
dissolve proteins and thus make it harder to identify different types
of neurons. Deisseroth’s group solved this problem by first infusing
the brain with acrylamide, which binds proteins, nucleic acids and
other biomolecules. When the acrylamide is heated, it polymerizes and
forms a tissue-wide mesh that secures the molecules. The resulting
brain–hydrogel hybrid showed only 8% protein loss after lipid
extraction, compared to 41% with existing methods.
Applying CLARITY to whole mouse brains, the researchers viewed
fluorescently labelled neurons in areas ranging from outer layers of
the cortex to deep structures such as the thalamus. They also traced
individual nerve fibres through 0.5-millimetre-thick slabs of
formalin-preserved autopsied human brain — orders of magnitude thicker
than slices currently imaged.
Kwanghun Chung & Karl Deisseroth, HHMI/Stanford Univ.
Neurons in an intact mouse hippocampus visualized using CLARITY and
“The work is spectacular. The results are unlike anything else in the
field,” says Van Wedeen, a neuroscientist at the Massachusetts General
Hospital in Boston and a lead investigator on the US National
Institutes of Health’s Human Connectome Project (HCP), which aims to
chart the brain’s neuronal communication networks. The new technique,
he says, could reveal important cellular details that would complement
data on large-scale neuronal pathways that he and his colleagues are
mapping in the HCP’s 1,200 healthy participants using magnetic
Francine Benes, director of the Harvard Brain Tissue Resource Center
at McLean Hospital in Belmont, Massachusetts, says that more tests are
needed to assess whether the lipid-clearing treatment alters or
damages the fundamental structure of brain tissue. But she and others
predict that CLARITY will pave the way for studies on healthy brain
wiring, and on brain disorders and ageing.
Researchers could, for example, compare circuitry in banked tissue
from people with neurological diseases and from controls whose brains
were healthy. Such studies in living people are impossible, because
most neuron-tracing methods require genetic engineering or injection
of dye in living animals. Scientists might also revisit the many
specimens in repositories that have been difficult to analyse because
human brains are so large.
The hydrogel–tissue hybrid formed by CLARITY — stiffer and more
chemically stable than untreated tissue — might also turn delicate and
rare disease specimens into reusable resources, Deisseroth says. One
could, in effect, create a library of brains that different
researchers check out, study and then return.
This was way back in 2013. These days they are making whole mice
transparent. How did I (we?) miss this?
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