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Ultrasound Imaging of Oxidative Stress In Vivo with Chemically-Generated Gas Microbubbles

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Abstract

Ultrasound contrast agents (UCAs) have tremendous potential for in vivo molecular imaging because of their high sensitivity. However, the diagnostic potential of UCAs has been difficult to exploit because current UCAs are based on pre-formed microbubbles, which can only detect cell surface receptors. Here, we demonstrate that chemical reactions that generate gas forming molecules can be used to perform molecular imaging by ultrasound in vivo. This new approach was demonstrated by imaging reactive oxygen species in vivo with allylhydrazine, a liquid compound that is converted into nitrogen and propylene gas after reacting with radical oxidants. We demonstrate that allylhydrazine encapsulated within liposomes can detect a 10 micromolar concentration of radical oxidants by ultrasound, and can image oxidative stress in mice, induced by lipopolysaccharide, using a clinical ultrasound system. We anticipate numerous applications of chemically-generated microbubbles for molecular imaging by ultrasound, given ultrasound’s ability to detect small increments above the gas saturation limit, its spatial resolution and widespread clinical use.

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Acknowledgments

This work was supported by NIH UO1 HL80711-01, (N.M.), NSF-BES-0546962 (N.M.), NIH U01 268201000043C-0-0-1 (N.M.) and NIH RO1, HL096796-01 (N.M.), NIHR01CA112356 (K.F.) and NIHCA103828 (K.F.). The authors would like to thank Dr. Lihong Cheng for assisting the setup for the clinical ultrasound system.

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Authors and Affiliations

  1. The Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA, 30332, USA

    John Kangchun Perng, Seungjun Lee, Kousik Kundu & Niren Murthy

  2. Department of Biomedical Engineering, University of California—Davis, Davis, CA, 95616, USA

    Charles F. Caskey & Katherine W. Ferrara

  3. Cardiology Division, School of Medicine, Emory University, Atlanta, GA, 30322, USA

    Sarah F. Knight, W. Robert Taylor & Daniel Sorescu

  4. School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA

    Sarp Satir & F. Levent Degertekin

  5. Atlanta VA Medical Center, Atlanta, GA, 30322, USA

    W. Robert Taylor

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  1. John Kangchun Perng
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  2. Seungjun Lee
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Correspondence to Niren Murthy.

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Associate Editor James Tunnell oversaw the review of this article.

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Perng, J.K., Lee, S., Kundu, K. et al. Ultrasound Imaging of Oxidative Stress In Vivo with Chemically-Generated Gas Microbubbles. Ann Biomed Eng 40, 2059–2068 (2012). https://doi.org/10.1007/s10439-012-0573-9

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  • DOI: https://doi.org/10.1007/s10439-012-0573-9

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