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

作者：Perng John Kangchun; Lee Seungjun; Kundu Kousik; Caskey Charles F; Knight Sarah F; Satir Sarp; Ferrara Katherine W; Taylor W Robert; Degertekin F Levent; Sorescu Daniel; Murthy Niren^*

来源：Annals of Biomedical Engineering, 2012, 40(9): 2059-2068.

DOI：10.1007/s10439-012-0573-9

• Ultrasound contrast agent
• Molecular imaging
• Reactive oxygen species (ROS)
• Oxidative stress
• Bubble nucleation
• Chemical gas generation

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.

• 出版日期2012-9