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Acoustically modulated magnetic resonance imaging of gas-filled protein nanostructures

Lu, George Jiaozhi and Farhadi, Arash and Szablowski, Jerzy O. and Lee-Gosselin, Audrey and Barnes, Samuel R. and Lakshmanan, Anupama and Bourdeau, Raymond W. and Shapiro, Mikhail G. (2018) Acoustically modulated magnetic resonance imaging of gas-filled protein nanostructures. Nature Materials, 17 (5). pp. 456-463. ISSN 1476-1122. PMCID PMC6015773. doi:10.1038/s41563-018-0023-7.

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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.

Item Type:Article
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URLURL TypeDescription ReadCube access CentralArticle
Lu, George Jiaozhi0000-0002-4689-9686
Farhadi, Arash0000-0001-9137-8559
Szablowski, Jerzy O.0000-0001-7851-5408
Lee-Gosselin, Audrey0000-0002-2431-2741
Barnes, Samuel R.0000-0002-1065-8442
Lakshmanan, Anupama0000-0002-6702-837X
Bourdeau, Raymond W.0000-0003-2202-1980
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:© 2018 Macmillan Publishers. Received: 15 July 2016. Accepted: 17 January 2018. Published online: 26 February 2018. 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. Author 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. Further information on experimental design is available in the Life Sciences Reporting Summary. Data and materials availability: Raw data, GVs and genetic constructs are available upon request to the authors. MATLAB scripts for Monte Carlo simulations are available at The authors declare no competing financial interests.
Group:Heritage Medical Research Institute
Funding AgencyGrant Number
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Dana FoundationUNSPECIFIED
Burroughs Wellcome FundUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC6015773
Record Number:CaltechAUTHORS:20171215-092640151
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Official Citation:Acoustically modulated magnetic resonance imaging of gas-filled protein nanostructures George J. Lu, Arash Farhadi, Jerzy O. Szablowski, Audrey Lee-Gosselin, Samuel R. Barnes, Anupama Lakshmanan, Raymond W. Bourdeau & Mikhail G. Shapiro Nature Materials (2018) doi:10.1038/s41563-018-0023-7
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:83937
Deposited By: George Porter
Deposited On:26 Feb 2018 18:16
Last Modified:15 Mar 2022 20:58

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