DARPA and Stanford Brain Imaging Collaboration helps to bring a new CLARITY to the world of Neuroscience

Thanks to a 100 million dollar grant through the White House Brain Mapping Project to the NIH, NSF, and DARPA (Defense Advanced Research Projects Agency), a dynamically new approach to how we view the brain has arisen: the CLARITY Brain Imaging Technique. With this technique, scientists are hoping to map brain connections on a large scale, visualizing how every single neuron is fired and interconnected with the other ones in the system. 

DARPA-Funded Research Offers Faster, Better Views of Entire Brain

A new research protocol developed at Stanford University in California improves on their previous technological breakthrough and lets neuroscientists visualize a brain across multiple scales, says program manager Dr. Justin Sanchez. Stanford scientists earlier developed a method called Clear, Lipid-exchanged, Acrylamide-hybridized Rigid, Imaging/immunostaining compatible, Tissue hydrogel (CLARITY) to study brain tissue. The method uses a chemical to transform intact biological tissues into a hydrogel hybrid, which makes the brain tissues transparent. “Brains are not clear to begin with, therefore if you’re trying to use, let’s say, a microscope to study the volume of tissue of the brain, the light can’t transverse through all of the structure,” Sanchez explains. “However, if you do ‘clarify’ it using this very novel technique, then you are able to get through a volume of tissue and study all of the circuitry.” Under the CLARITY protocol, Sanchez says, it could take upwards of 80 years to conduct the imaging process for a complete human brain. But the new protocol accelerates the process so that the same technique now takes 220 days.

Seeing the inner workings of the brain made easier by new technique from Stanford scientists

When you look at the brain, what you see is the fatty outer covering of the nerve cells within, which blocks microscopes from taking images of the intricate connections between deep brain cells. The idea behind CLARITY was to eliminate that fatty covering while keeping the brain intact, complete with all its intricate inner wiring. To help expand the use of CLARITY, the team devised an alternate way of pulling out the fat from the hydrogel-embedded brain – a technique they call passive CLARITY. It takes a little longer, but still removes all the fat, is much easier and does not pose a risk to the tissue. "Electrophoretic CLARITY is important for cases where speed is critical, and for some tissues," said Deisseroth, who is also the D.H. Chen Professor. "But passive CLARITY is a crucial advance for the community, especially for neuroscience." Passive CLARITY requires nothing more than some chemicals, a warm bath and time. Many groups have begun to apply CLARITY to probe brains donated from people who had diseases like epilepsy or autism, which might have left clues in the brain to help scientists understand and eventually treat the disease. But scientists, including Deisseroth, had been wary of trying electrophoretic CLARTY on these valuable clinical samples with even a very low risk of damage. "It's a rare and precious donated sample, you don't want to have a chance of damage or error," Deisseroth said. "Now the risk issue is addressed, and on top of that you can get the data very rapidly."

Fat-free see-through brain bares all

A breakthrough method, called CLARITY, developed by National Institutes of Health-funded researchers, opens the intact postmortem brain to chemical, genetic and optical analyses that previously could only be performed using thin slices of tissue. By replacing fat that normally holds the brains working components in place with a clear gel, they made its normally opaque and impenetrable tissue see-through and permeable. This made it possible to image an intact mouse brain in high resolution down to the level of cells and molecules. The technique was even used successfully to study a human brain.