New Technique Makes Brains Transparent for Science (w/videos)

Scientists who study the physical structure of the brain typically slice the organ into thin sections that are then digitized and analyzed using specialty software that allows rendering of 3D volumes. Yet, just like with walls, the only reason we can’t see through brains is because they are opaque. This may sound like a tautology, a fact of life that will always be, yet it turns out that the main reason brain tissue is not transparent is its lipid content.

Taking note of this fact, researchers at Stanford University developed a chemical process of removing fat content from brain tissue and replacing it with a mix of formaldehyde, a hydrogel, and other ingredients. Called Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue Hydrogel, or CLARITY, the technique should be effective for other tissue types, allowing both structural and molecular analysis while preserving the 3D shape and functional integrity of the samples.

 

Here’s an interview with Karl Deisseroth, MD, PhD, the lead author of the study:

A couple videos showing off imaging done on a transparent mouse brain:

CLARITY provided this 3D view showing a thick slice of a mouse brain’s memory hub, or hippocampus. It reveals a few different types of cells: projecting neurons (green), connecting interneurons (red), and layers of support cells, or glia (blue). Conventional 2D methods require that brain tissue be thinly sliced, sacrificing the ability to analyze such intact components in relation to each other. CLARITY permits such typing of molecular and cellular components to be performed repeatedly in the same brain. Source: Karl Deisseroth, Stanford University

 

CLARITY makes possible this 3D tour of an entire, intact mouse brain. It was imaged using a fluorescence technique that previously could only be performed with thinly-sliced brain tissue, making it difficult to relate micro-level findings to macro-level information about wiring and circuitry. Source: Karl Deisseroth, Stanford University

Study in Nature: Structural and molecular interrogation of intact biological systems

NIH announcement: Fat-free see-through brain bares all…

More from Stanford Medicine Scope Blog: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact