Enhanced Detection of Thromboemboli With the Use of Targeted Microbubbles

Background and Purpose: Targeted ultrasound contrast agents have recently been developed to adhere selectively to specific pathogenic materials such as plaque or thrombus. Administration of such microbubbles has potential to aid transcranial Doppler ultrasound (TCD) detection of emboli, and to act as markers for distinguishing one embolic material from another. The purpose of this study was to investigate whether TCD detection of circulating thrombus emboli would be enhanced by the addition of targeted microbubbles. Methods: Binding of microbubbles to the surface of the thrombus was confirmed using Scanning Electron Microscopy. Targeted and control bubbles were then introduced to thrombus and tissue-mimicking material circulated under pulsatile flow conditions in an in vitro flow-rig. Embolic signal intensities before and after introduction of the bubbles were measured using transcranial Doppler ultrasound. Results: Targeted microbubbles enhanced Doppler signal intensities from thrombus emboli by up to 13 dB. The bubbles were capable of binding to moving thrombus when injected into the flow-circuit in low concentrations (~ 30 bubbles per 100 ml), and were retained on the thrombus under pulsatile-flow conditions. Signal intensities from similarly sized pieces of tissue mimicking material were not enhanced by injection of targeted bubbles. Conclusions: Injection of appropriately targeted microbubbles significantly enhances ultrasound detection of circulating thrombus emboli in vitro, and has potential to assist clinicians in distinguishing thrombus emboli from atheromatous plaque.