A technique for rendering whole animals - such as rats or mice - transparent, so that the intact nervous system or entire organs can be imaged in place within the body, is described in Nature Methods. It is the first tissue-clearing method that allows imaging of whole animals, and it has various biomedical applications for studying the organization of large organ systems.
Traditionally, techniques for studying the cellular structure of deep tissues in animals have relied on slicing the tissue into thin sections and then imaging those sections. However, the study of more complex and nonuniformly shaped cells, such as those in the central nervous system, is best performed with intact tissue. Tissue-clearing approaches address this need, but they still present limitations for imaging large samples (such as a rodent body). The method that achieves the highest level of tissue transparency - 3D imaging of solvent-cleared organs (3DISCO) - also greatly reduces the size of the specimen, but it rapidly extinguishes any fluorescent proteins expressed in the animal.
Ali Erturk and colleagues have developed an improved method that overcomes these limitations, which they call ultimate DISCO (uDISCO). They find that uDISCO preserves fluorescent proteins for months while also rendering organs and rodent bodies transparent and reducing their size by up to 65%. They use uDISCO to image entire bodies of adult rodents, mapping long-distance (over 7 cm) nerve connections and vascular systems. They find that the method does not alter the structural integrity of the brain at either macroscopic (such as the cortex and hippocampus structures) or microscopic (for example, individual cells) scales. Finally, the authors suggest that, through the development of whole mouse atlases and databases, their method may help reduce the number of animals required in research.
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