Researchers from Japan's RIKEN Quantitative Biology Center and the University of Tokyo have developed a means of taking highly detailed images of interior organs by combining light-sheet fluorescent microscopy and tissue decolorization.
Profiled in the journal Cell, the study allowed researchers to make tissues and even whole organisms transparent, opening up possibilities for understanding how life works. CUBIC or Clear, Unobstructed Brain Imaging Cocktails and Computational Analysis was used before for imaging brains and utilized by researchers for this study.
While the brain contains a lot of lipids and thus can easily be cleared by different methods, other body parts feature molecular sub-units called chromophores, which can absorb light. Heme, a chromophore, is a component of hemoglobin and is present in most bodily tissues. Heme also blocks light.
Researchers were surprised to discover that the chromophore reacted with the aminoalcohols in the CUBIC reagent, dissolving to turn organs drastically more transparent. The scientists then took images of mouse livers, kidneys, lungs, hearts, and brains and attempted to turn adult and infant mice transparent. They were successful in creating transparent mice and were able to take "slices" of tissues to render 3D images of organs.
To test if the method is practical, researchers examined the pancreas of both diabetic and non-diabetic mice. They saw clearly the structures of the organ where insulin is produced, observing in detail the difference between the isles of Langerhans in the pancreases.
Although CUBIC can't be used on living organisms, Kazuki Tainaka, first author for the study, said that their work can be very useful in creating 3D versions of organs, allowing for a more thorough understanding of how genes are expressed in different tissues. Cellular networks within tissues are also more readily observable in the adult and infant mice, addressing major challenges in medicine and biology by making it possible to literally see more clearly inside.
"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," explained Hiroki Ueda, lead researcher for the study.
Aside from Ueda and Tainaka, other authors for the study include Shimpei Kubota, Hideki Ukai, Takeru Suyama, Maki Ukai-Tadenuma, Etsuo Susaki and Dimitri Perrin.
