It is now possible to see through large tissue samples under a microscope with a technique that strips cells of their light-blocking parts. The technique, developed at the California Institute of Technology, could enable new diagnostic medical applications, including better imaging of developmental problems and diseases. Through the new PARS technique, researchers can make the body, including cells and tissue, transparent for better imaging and analysis. Images courtesy of Bin Yang and Viviana Gradinaru/ California Institute of Technology. “Large volumes of tissue are not optically transparent. You can’t see through them,” said Dr. Viviana Gradinaru, an assistant professor of biology at Caltech. “If we need to see individual cells within a large volume of tissue, we have to slice the tissue very thin, separately image each slice with a microscope, and put all of the images back together with a computer." This shows 3-D visualization of fluorescently labeled kidney cells within kidney tissue. Lipids in cells provide structural support, but also prevent light from passing through. The new technique, called PARS (perfusion-assisted agent release in situ), involves infusing a sample with a solution of lipid-dissolving detergents. These render the cells transparent, while hydrogel in the solution provides structural support in place of the lipids. Confocal and other microscopy methods can then be applied, and single cells marked with fluorescent proteins can be imaged. When whole-body transparency is not necessary, another method called PACT (passive clarity technique) is equally effective with individual organs, the researchers said. This 3-D visualization demonstrated fluorescently labeled intestine cells in intact intestine tissue. Applications that could benefit from the new techniques include the rapid detection of cancer cells in biopsy samples, as well as mapping peripheral nervous system neurons or disease distributions in animal models. “I think these new techniques are very practical for many fields in biology,” Gradinaru said. “When you can just look through an organism for the exact cells or fine axons you want to see, without slicing and realigning individual sections, it frees up the time of the researcher.” The research was published in Cell (doi: 10.1016/j.cell.2014.07.017). For more information, visit www.caltech.edu.