Vascular damage by ultrasound-activated microbubble induced vesselinvagination

Vascular bioeffects produced by ultrasound contrast agent microbubbles areprimarily manifested as damage to microvessels. The objective of this work is todirectly observe the transient dynamics of bubble-vessel interactions andcorrelate the observed interactions with associated vascular damage.Microbubbles were perfused into microvessels in ex vivo rat mesenteries and thenexcited by a single 2 s long ultrasound pulse at 1 MHz. Meanwhile, 14high-speed photomicrographic images were acquired using 50 ns shutter speeds.The targeted region was then examined by histology and transmission electronmicroscopy (TEM). Image registration was used to identify the specific vesselsthat the corresponding high-speed images were captured. The recorded high-speedimages revealed that bubble-vessel interactions caused vessel wall distention(motion outward against the surrounding tissue) and invagination (motion inwardtoward the lumen). Invagination exceeding distention was observed in 60 out of70 cases. Significant vessel invagination was correlated with vascular damagethat was characterized by a separation of the endothelium from the surroundingtissue as revealed by both the histology and TEM analyses. The separation of theendothelium from the surrounding tissue is consistent with damage caused bytensile stresses at the vessel walls that lead to vessel invagination. Thissuggests that invagination may be an important mechanism by which microbubblescause vascular damage.