An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels.

A novel experimental model which uses an isolated, cannulated rat mesenteric artery (∼ 400 μm diameter) has been used for the visualization of vessel behavior and damage during therapeutic ultrasound (US) exposures in the presence of contrast agents. The experimental setup includes a fluorescence microscope, ultrasound transducer, and a chamber in which the vessel, attached to micropipettes, can be perfused with a feeding buffer ± contrast agents and fluorescent dyes. A range of continuous and pulsed 1.7 MHz high intensity focused ultrasound (HIFU) exposures have been used at therapeutic and sub-therapeutic intensities (pressures). Vessel wall damage and leakage of intravascular buffer have been observed, predominantly in the presence of contrast agents. The observed lack of vascular constriction and expansion in response to phenylephrine and acetylcholine indicates smooth muscle and endothelial cell damage. This has been confirmed by histology (haematoxylin and eosin staining) and immunohistochemistry. Factor VIII and alpha-actin antibodies (which have receptors localised on endothelial, and smooth muscle cells respectively) have been used for accurate localisation of HIFU affected areas. This model will be also used to investigate the bio-effects induced by the exposure of vessels to diagnostic US exposures in the presence of contrast agents.