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

• Type of Material: Article
• Authors: John Kangchun Perng, Georgia Institute of Technology; Seungjun Lee, Georgia Institute of Technology; Kousik Kundu, Georgia Institute of Technology; Charles F. Caskey, University of California at Davis; Sarah F. Knight, Emory University; Sarp Satir, Georgia Institute of Technology; Katherine W. Ferrara, University of California at Davis; W Robert Taylor, Emory University; F. Levent Degertekin, Georgia Institute of Technology; Dan Sorescu, Emory University; Niren Murthy, Georgia Institute of Technology
• Language: English
• Date: 2012-09-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Biomedical Engineering Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s10439-012-0573-9
• Title of Journal or Parent Work: Annals of Biomedical Engineering
• ISSN: 0090-6964
• Volume: 40
• Issue: 9
• Start Page: 2059
• End Page: 2068
• Grant/Funding Information: This work was supported by NIH UO1 HL80711-01, (N.M.), NSF-BES-0546962 (N.M.), NIH U01 268 201000043C-0-0-1 (N.M.) and NIH RO1, HL096796-01 (N.M.), NIHR01CA112356 (K.F.) and NIHCA103828 (K.F.).
• Keywords: LIQUIDS; Chemical gas generation; Oxidative stress; Reactive oxygen species (ROS); RETRO-ENE REACTIONS; CONTRAST AGENTS; WATER; Molecular imaging; Engineering; Engineering, Biomedical; Science & Technology; OSCILLATIONS; Ultrasound contrast agent; BUBBLE NUCLEATION; Technology; INSTABILITIES; HOMOGENEOUS NUCLEATION; DISSOLUTION; Bubble nucleation; SUPERSATURATED SOLUTIONS
• Research Categories: Engineering, Biomedical; Health Sciences, General; Engineering, Mechanical

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.