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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 laboratoryResearchers 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 inCell, 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 tissue 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 adult mice, and found that in all cases they could get clear tissues. They used the technique of light-sheet fluorescent microscopy, 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.

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