title: Ultrasound imaging of oxidative stress in vivo with chemically-generated gas microbubbles.
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.
authors.affiliation: 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.
authors.forename: John Kangchun
authors.initials: JK
authors.lastname: Perng
authors.forename: Seungjun
authors.initials: S
authors.lastname: Lee
authors.forename: Kousik
authors.initials: K
authors.lastname: Kundu
authors.forename: Charles F
authors.initials: CF
authors.lastname: Caskey
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Knight
authors.forename: Sarp
authors.initials: S
authors.lastname: Satir
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: F Levent
authors.initials: FL
authors.lastname: Degertekin
authors.forename: Daniel
authors.initials: D
authors.lastname: Sorescu
authors.forename: Niren
authors.initials: N
authors.lastname: Murthy
mesh_terms: D000475:Alkenes / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D005704:Gallbladder / Q000000981:diagnostic imaging* / Q000378:metabolism; D006834:Hydrazines / Q000008:administration & dosage* / Q000737:chemistry; D017665:Hydroxyl Radical / Q000008:administration & dosage*; D007249:Inflammation / Q000139:chemically induced; D008070:Lipopolysaccharides; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D057054:Molecular Imaging; D009584:Nitrogen / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013451:Sulfonic Acids / Q000737:chemistry; D014463:Ultrasonography
chemical_list: D000475:Alkenes; D052160:Benzothiazoles; D003287:Contrast Media; D006834:Hydrazines; D008070:Lipopolysaccharides; D008081:Liposomes; D017382:Reactive Oxygen Species; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D017665:Hydroxyl Radical; C006467:allylhydrazine; C013658:propylene; D009584:Nitrogen