Ultrasound imaging of oxidative stress in vivo with chemically generated gas microbubbles
Perng, John Kangchun
MetadataShow full item record
Ultrasound contrast agents (UCA) have tremendous potential for in vivo molecular imaging because of their high sensitivity and great spatial resolution of ultrasound imaging. However, the diagnostic potential of UCAs has been difficult to exploit because current contrast agents are based on pre-formed microbubbles, which can only detect cell surface receptors. In this work, we demonstrated that chemical reactions that generate gas forming molecules can be used to perform molecular imaging by ultrasound in vivo. This new approach for generating ultrasound contrast agents was demonstrated by imaging reactive oxygen species (ROS) in vivo with allylhydrazine, a compound that is converted into nitrogen and propylene gas after reacting with radical oxidants. We demonstrated that allylhydrazine encapsulated within liposomes (termed APLs) can detect a 10 uM concentration of radical oxidants by ultrasound, and can image oxidative stress in mice, induced by lipopolysaccharide (LPS), using a clinical ultrasound machine. We showed that a 1-2% increase in gas concentration above saturation can be detected acoustically and suggest that numerous biological targets can be imaged via appropriately designed gas forming reactions. This work was the first demonstration of in vivo imaging of ROS using ultrasound, and this work presented a new strategy to generate gas bubbles from reactions involving radical oxidants. We anticipate numerous applications of chemically generated microbubbles, given the excellent spatial resolution of ultrasound imaging, its widespread clinical use and its high sensitivity to detect gas bubbles.