Japan scientists make see-through mice

November 6, 2014, RIKEN
This picture released from Japanese research institute Riken on November 6, 2014 shows a decolorized mouse body and some organs glowing with fluorescence protein at the Riken laboratory

Researchers at the RIKEN Quantitative Biology Center in Japan, together with collaborators from the University of Tokyo, have developed a method that combines tissue decolorization and light-sheet fluorescent microscopy to take extremely detailed images of the interior of individual organs and even entire organisms. The work, published in Cell, opens new possibilities for understanding the way life works—the ultimate dream of systems biology—by allowing scientists to make tissues and whole organisms transparent and then image them at extremely precise, single-cell resolution.

To achieve this feat, the researchers, led by Hiroki Ueda, began with a method called CUBIC (Clear, Unobstructed Brain Imaging Cocktails and Computational Analysis), which they had previously used to image whole brains. Though brain is lipid-rich, and thus susceptible to many clearance methods, other parts of the body contain many molecular subunits known as chromophores, which absorb light. One chromophore, heme, which forms part of hemoglobin, is present in most tissues of the body and blocks light. The group decided to focus on this issue and discovered, in a surprise finding, that the aminoalcohols included in the CUBIC reagent could elute the heme from the hemoglobin and by doing so make other organs dramatically more transparent.

Using the method, they took images of mouse brains, hearts, lungs, kidneys, and livers, and then went on to attempt the method on infant and , and found that in all cases they could get clear tissues. They used the technique of light-sheet , which involves taking "slices" of tissues without having to actually cut into it, to gain 3D images of the organs. To test the practicability of the method, they examined the pancreases of diabetic and non-diabetic mice, and found clear differences in the isles of Langerhans, the structures in the pancreas that produce insulin.

Although these methods could not be used in living organisms, since they require the tissues to be fixed using reagents, they could, according to Kazuki Tainaka, the first author of the paper, be very useful for gaining new understanding of the 3D structure of organs and how certain genes are expressed in various tissues. He said, "We were very surprised that the entire body of infant and adult mice could be made nearly transparent by a direct transcardial CUBIC perfusion coupled with a two-week clearing protocol. It allowed us to see cellular networks inside tissues, which is one of the fundamental challenges in biology and medicine."

This picture released by Japanese research institute Riken on November 6, 2014 shows a decolorized mouse body at the Riken laboratory

According to Hiroki Ueda, who led the research team, "This new method could be used for 3D pathology, anatomical studies, and immunohistochemistry of entire organisms. For example, it could be used to study how embryos develop or how cancer and autoimmune diseases develop at the cellular level, leading to a deeper understanding of such diseases and perhaps to new therapeutic strategies. It could lead to the achievement of one of our great dreams, organism-level systems biology based on whole-body imaging at single-cell resolution."

Though it is an important finding, more work lies ahead. In the future, the group plans to make improvements to the microscopy to allow for the rapid imaging of whole bodies of adult mice or larger samples such as human brains, and to apply this technology to further our understanding of autoimmune and psychiatric diseases.

Explore further: Rapid whole-brain imaging with single cell resolution

Related Stories

Rapid whole-brain imaging with single cell resolution

April 17, 2014

A major challenge of systems biology is understanding how phenomena at the cellular scale correlate with activity at the organism level. A concerted effort has been made especially in the brain, as scientists are aiming to ...

Biology made simpler with "clear" tissues

August 4, 2014

(Phys.org) —In general, our knowledge of biology—and much of science in general—is limited by our ability to actually see things. Researchers who study developmental problems and disease, in particular, are often limited ...

Improving the view through tissues and organs

October 17, 2014

This summer, several undergraduate students at Caltech had the opportunity to help optimize a promising technique that can make tissues and organs—even entire organisms—transparent for study. As part of the Summer Undergraduate ...

Improving imaging of cancerous tissues by reversing time

November 2, 2014

As a child, it was fascinating to put a flashlight up to our palms to see the light shine through the hand. Washington University in St. Louis engineers are using a similar idea to track movement inside the body's tissues ...

New chemical reagent turns mouse brain transparent

August 31, 2011

Japanese researchers at RIKEN have developed a ground-breaking new aqueous reagent which literally turns biological tissue transparent. Experiments using fluorescence microscopy on samples treated with the reagent, published ...

Recommended for you

Triplefin fish found to have controlled iris radiance

February 21, 2018

A team of researchers with the University of Tübingen in Germany has found an example of a fish that is able to control light reflected from organs next to its pupils—a form of photolocation. In their paper published in ...

New insight into plants' self-defense

February 21, 2018

Chloroplasts are the ultimate green machines—the parts of plant cells that turn sunlight into food in a fairly famous process known as photosynthesis.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Bob48
not rated yet Nov 06, 2014
What no pictures!?!
tritace
Nov 06, 2014
This comment has been removed by a moderator.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.