Abstract

Non-invasive biological imaging requires materials capable of interacting with deeply penetrant forms of energy such as magnetic fields and sound waves. Here, we show that gas vesicles (GVs), a unique class of gas-filled protein nanostructures with differential magnetic susceptibility relative to water, can produce robust contrast in magnetic resonance imaging (MRI) at sub-nanomolar concentrations, and that this contrast can be inactivated with ultrasound in situ to enable background-free imaging. We demonstrate this capability in vitro, in cells expressing these nanostructures as genetically encoded reporters, and in three model in vivo scenarios. Genetic variants of GVs, differing in their magnetic or mechanical phenotypes, allow multiplexed imaging using parametric MRI and differential acoustic sensitivity. Additionally, clustering-induced changes in MRI contrast enable the design of dynamic molecular sensors. By coupling the complementary physics of MRI and ultrasound, this nanomaterial gives rise to a distinct modality for molecular imaging with unique advantages and capabilities.

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Acknowledgements

We acknowledge Arnab Mukherjee, Pradeep Ramesh, Hunter Davis, Russell Jacobs, Xiaowei Zhang and Michael Tyszka for helpful discussions. A.F. acknowledges financial support from the Natural Sciences and Engineering Research Council of Canada. A.L. acknowledges financial support from National Science Foundation. This project was supported by the National Institutes of Health (grant EB018975). M.G.S. also acknowledges funding from the Dana Foundation, the Burroughs Wellcome Career Award at the Scientific Interface, the Packard Fellowship in Science and Engineering and the Heritage Medical Research Institute.

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Affiliations

  1. Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA

    • George J. Lu
    • , Jerzy O. Szablowski
    • , Audrey Lee-Gosselin
    • , Raymond W. Bourdeau
    •  & Mikhail G. Shapiro
  2. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA

    • Arash Farhadi
    •  & Anupama Lakshmanan
  3. Department of Radiology, Loma Linda University, Loma Linda, CA, USA

    • Samuel R. Barnes

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Contributions

G.J.L. and M.G.S. conceived the study. G.J.L., A.F. and J.O.S., A.L.G. and M.G.S. designed, planned and carried out the experiments and analysed data. S.B. provided software for QSM analysis. A.L. and R.W.B. provided reagents. All authors discussed the results. G.J.L. and M.G.S. wrote the manuscript with input from all authors. All authors have given approval to the final version of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Mikhail G. Shapiro.

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https://doi.org/10.1038/s41563-018-0023-7

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