TY - JOUR
T1 - Ultrasound imaging of oxidative stress in vivo with chemically-generated gas microbubbles
AU - Perng, John Kangchun
AU - Lee, Seungjun
AU - Kundu, Kousik
AU - Caskey, Charles F.
AU - Knight, Sarah F.
AU - Satir, Sarp
AU - Ferrara, Katherine W.
AU - Taylor, W. Robert
AU - Degertekin, F. Levent
AU - Sorescu, Daniel
AU - Murthy, Niren
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Bubble nucleation
KW - Chemical gas generation
KW - Molecular imaging
KW - Oxidative stress
KW - Reactive oxygen species (ROS)
KW - Ultrasound contrast agent
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U2 - 10.1007/s10439-012-0573-9
DO - 10.1007/s10439-012-0573-9
M3 - Article
C2 - 22562306
AN - SCOPUS:84865130085
VL - 40
SP - 2059
EP - 2068
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 9
ER -