Abstract
A long-standing goal of molecular imaging is to visualize cellular function within the context of living animals, necessitating the development of reporter genes compatible with deeply penetrant imaging modalities such as ultrasound and magnetic resonance imaging (MRI). Until recently, no reporter genes for ultrasound were available, and most genetically encoded reporters for MRI were limited by metal availability or relatively low sensitivity. Here we review how these limitations are being addressed by recently introduced reporter genes based on air-filled and water-transporting biomolecules. We focus on gas-filled protein nanostructures adapted from buoyant microbes, which scatter sound waves, perturb magnetic fields and interact with hyperpolarized nuclei, as well as transmembrane water channels that alter the effective diffusivity of water in tissue.