High-resolution imaging of biological tissue has traditionally required sectioning, which for tissues like the brain means the loss of long-range connectivity. Now Karl Deisseroth and colleagues have developed a way of making full, intact organs optically transparent and macromolecule-permeable by building a hydrogel-based infrastructure from within the tissue that allows subsequent removal of light-scattering lipids, resulting in a transparent brain. The method, termed CLARITY, also allows repeated antibody labeling of proteins, and in situ hybridization of nucleic acids in non-sectioned tissue, such as full mouse brains or human clinical samples stored in formalin for many years. CLARITY enabled fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for analysis of physiological function and disease.
Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ, Mirzabekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K: Structural and molecular interrogation of intact biological systems. Nature [Epub ahead of print, April 10, 2013; doi: 10.1038/nature12107].