Ultra high-speed fluorescence imaging of ultrasound contrast agents for imaging and therapy

Given the poor optical contrast of bright field imaging, fluorescence imaging is required to image ultrasound microbubbles in stratified vascular flows and to visualize drug release from loaded capsules. Fluorescence recordings using a combination of a high power CW laser and the Brandaris 128 ultra high-speed imaging facility give unique insight into the physical mechanisms of local intravascular drug delivery. Recordings of fluorescently labeled phospholipid-coated contrast agents show an excellent delineation of the bubble wall at frame rates of up to 5 million frames per second. This allowed us to reveal the time-resolved dynamic distribution of the shell material, including lipid shedding. Oil-filled polymeric microcapsules with a high dye concentration mixed in the hexadecane liquid core demonstrate a profound photo-acoustic effect when excited with a laser intensity of 1 MW/cm 2 or higher. The dye molecules absorb the laser light leading to intense heating of the liquid core. A rapid phase change leads to an impulsive thermal expansion. The resulting vapor bubble dynamics imaged using fluorescence imaging at a timescale of 100 nanoseconds revealed a typical oscillation frequency of 220 kHz. The generated acoustic pressure is in the order of 100 Pa at a distance of 2.5 cm from the capsule