Li, L. et al. Nat. Commun. 9, 2734 (2018).

Photoacoustic imaging (PAI) has emerged as a powerful method for sensitive and high-resolution imaging in vivo, but the development of genetically encoded probes for PAI has lagged behind that for fluorescence imaging. Li et al. report the engineering of a photoswitchable near-infrared fluorescent protein for improved photoacoustic computed tomography (PACT). The protein, DrBphP-PCM, is based on bacterial DrBphP but is an improvement over that phytochrome in that it is smaller, folds better, and gives higher photoswitching contrast. The researchers showed that DrBphP-PCM outperforms DrBphP for imaging deep within the mouse brain and can be used in multiplexed PACT. They also used DrBphP-PCM as the basis for a split version of the protein, termed DrSplit, which enabled the detection of protein–protein interactions deep within tissues. These new probes should provide versatile tools for deep-tissue imaging.