Boothe, T. et al. eLife 6, e27240 (2017).

Mismatches in refractive index (RI) between biological specimens and their surrounding media can lead to problems during imaging such as spherical aberrations that negatively impact image quality and fidelity. These aberrations are often worse for thick and complex samples and can hinder deep imaging. Boothe et al. developed an approach to correct for RI mismatches in live imaging. Their approach involved identifying a chemical compound with high water solubility and low toxicity with a high RI that could be mixed with sample media to tune the RI of the media. The compound they identified and demonstrated to meet these criteria was Iodixanol. They found that Iodixanol has low toxicity on a number of samples, including developing zebrafish, and that RI matching with Iodixanol improves image resolution and signal-to-noise at greater tissue depths.