Microbubble dynamics in microvessels: Observations of microvessel dilation, invagination and rupture

Understanding the interaction of acoustically activated microbubbles with small blood vessels is important for designing better imaging schemes, and for targeting and drug delivery applications. To understand the fundamental mechanisms of this interaction, high-speed microscopy was used to observe microbubble dynamics in microvessels of ex vivo rat mesenteries exposed to a single pulse of ultrasound with a center frequency of 1 MHz and peak negative pressure (PNP) of 1.2 MPa or 11 MPa. It was found that microbubble oscillation caused adjacent microvessel dilation, invagination and even rupture on a microsecond time scale. In small microvessels, microbubble contacted with the vessel wall during expansion under both low and high pressure levels, and microvessel dilation generated by microbubble expansion was larger than invagination induced by bubble collapse. Specifically, under 11 MPa PNP insonation, a small microvessel (17 mum) dilated to 2.7times, and then invaginated to 0.4times of its original diameter, followed by extravasation of re-expanding daughter microbubbles indicating that the microvessel had been ruptured. For large microvessels, microbubbles did not contact with the vessel wall during expansion, and generated much less dilation than invagination at both pressure levels. In one case, a large microbubble caused the wall of a 100 mum microvessel to form a jet-like structure during invagination.