Proteins, air and water: reporter genes for ultrasound and magnetic resonance imaging

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.

Molecular Sensing with Host Systems for Hyperpolarized 129Xe

“…The acoustic impedance mismatch occurring between the gas interior of GVs with surrounding aqueous media makes the GVs to strongly scatter sound waves, a prerequisite for using them as ultrasound (US) contrast agents as their initial imaging application [ 255 , 442 , 443 , 444 , 445 ]. These GVs generate robust US contrast across a range of frequencies at pM concentrations and also exhibit harmonic scattering that enable enhanced detection without any background in vivo [ 255 ].…”

“…Interestingly, the MR contrast generated by susceptibility measurements of GVs can be modulated using ultrasound (US) in order to avoid background interference. Additionally, the acoustic properties of GVs were utilized in 1 H MRI where the serial acoustic collapse of GVs engineered with certain collapse thresholds were performed to achieve multiplexed imaging [ 445 ]. This option could also be included in Xe MRI detection protocols.…”

Metabolic Labeling of Peptidoglycan with NIR‐II Dye Enables In Vivo Imaging of Gut Microbiota

“…Moreover, in vivo bacterial imaging by detecting bioluminescence often had unsatisfactory spatial resolution . Bacteria engineered with acoustic reporter proteins, which could form hollow nanostructures inside bacteria and respond to ultrasound detection, exhibited improved spatial resolution and suitability to anaerobic environment . Notwithstanding these advantages, the use of this method, like other genetic engineering strategies, is limited to genetically modifiable bacteria, which currently account for only a very small proportion of intestinal bacteria.…”

Accomplishments and challenges in stem cell imaging in vivo

“…Inspired by gas-vesicle-forming photosynthetic microbes, which produce these vesicles to control the organisms' buoyancy, Shapiro et al characterized these gas vesicles that also contain iron and showed that they are active as US and MRI contrast agents [94][95][96]. The genetic precursors of these complex protein vesicles were then determined and used as a US and MRI gene reporter system [96]. The extremely high sensitivity of US should prove to be a powerful tool to label and track SCs.…”