CLARITY process: interview with Stanford bioengineer and psychiatrist Karl Deisseroth. Length: 3:58

The process, called CLARITY, ushers in an entirely new era of whole-organ imaging that stands to fundamentally change our scientific understanding of the most important but least understood of organs, the brain, and potentially other organs, as well.

The process is described in a paper published online April 10 in Nature by bioengineer and psychiatrist Karl Deisseroth, MD, PhD, leading a multidisciplinary team, including postdoctoral scholar Kwanghun Chung, PhD.

The research in this study was performed primarily on a mouse brain, but the researchers have used CLARITY on zebrafish and on preserved human brain samples with similar results, establishing a path for future studies of human samples and other organisms.

The mound of convoluted grey matter and wiring that is the brain is a complex and inscrutable place. Neuroscientists have struggled to fully understand its circuitry in their quest to comprehend how the brain works, and why, sometimes, it doesnt.

Neuroscientists would have liked to extract the lipids to reveal the brains fine structure without slicing or sectioning, but for one major hitch: removing these structurally important molecules causes the remaining tissue to fall apart.

Prior investigations have focused instead on automating the slicing/sectioning approach, or in treating the brain with organic molecules that facilitate the penetration of light only, but not macromolecular probes. With CLARITY, Deisseroths team has taken a fundamentally different approach.

CLARITY then goes one better. In preserving the full continuity of neuronal structures, CLARITY not only allows tracing of individual neural connections over long distances through the brain, but also provides a way to gather rich, molecular information describing a cells function that is not possible with other methods.

A three-dimensional rendering of clarified brain imaged from below (ventral half). A fly-through video of rodent brain is available here.

And in yet another significant capability from a research standpoint, researchers are now able to destain the clarified brain, flushing out the fluorescent antibodies and repeating the staining process anew using different antibodies to explore different molecular targets in the same brain. This staining/destaining process can be repeated multiple times, the authors showed, and the different data sets aligned with one another.

Three-dimensional view of stained hippocampus showing fluorescent-expressing neurons (green), connecting interneurons (red) and supporting glia (blue).

Stanfords Department of Bioengineering also supported the work. The department is jointly operated by the School of Engineering and the School of Medicine.

Andrew Myers is the associate communications director for the School of Engineering.