The polydisperse acoustic signature of rigid microbubbles.

Microbubbles are used in medical ultrasound imaging as contrast agents to image the vascular bed under the mode of Ultrasound Contrast Imaging (UCI). The microbubble shell determines the acoustic response and hence the signal that is utilized to form the images in UCI. Single microbubble signals from BiSphere™ (POINT Biomedical, San Carlos, CA, USA) microbubbles were captured using a clinical ultrasound system. Three main typical responses of microbubbles were identified, a) full duration echo, b) echo with duration shorter than the incident pulse and c) echo that in part resembles that in (b) and in addition prior to that another short duration initial lower amplitude signal. These data corroborate that the shell structural and nanomechanical property provide the different responses at different microbubble sizes. These different signals present an opportunity for tracking the movement of well differentiated single microbubbles particularly with novel super-resolution imaging methods that require sparse microbubble populations.

A setup for the assessment of the effect of tubular confinement on the acoustic response of microbubbles.

Ultrasound contrast agents are gas filled microbubbles which produced enhanced echoes in ultrasound imaging thus allowing the acquisition of detailed information on the path of blood. It is theoretically known that the size of a vessel affects the behavior of a microbubble, which could potentially be used to discriminate different sized vessels. This information would be useful in the monitoring of neovascularization in tumor growth or treatment. However, currently it is not possible to identify the vessel diameter by any means of signal processing of microbubble echoes. In order to assess microbubble behavior when confined in tubes we compared the acoustic backscatter from biSphere™ microbubbles both free in water and flowing in 200 µm diameter tubes that are similar in size to arterioles. Experimental systems that allow the interrogation of individual microbubbles were designed and modified to allow investigation of both free microbubbles and those in tubes. Unprocessed single microbubble RF data were collected, allowing the calculation of both the fundamental and second harmonic components of the backscattered signal. Microbubbles confined in tubes had lower amplitude response compared to unconfined microbubbles. On consecutive insonations of the same microbubble, free microbubbles produced echoes above noise more often than confined microbubbles. This setup may be used to investigate microbubble behavior in a range of smaller tubes with diameters similar to capillaries thus enabling signal processing design for vessel differentiation.