In vivo microbubble cavitation imaging

Stroke is the second cause of death and a leading cause of disability worldwide. Less than 5% of ischemic stroke patients receive the state-of-the art treatment of a thrombolytic drug tPA, and only about 10% of these gain additional benefit from it. Ultrasound (US)-induced microbubble (MB) cavitation has been shown to enhance the efficacy of the tPA drug, and dissolve clots without tPA. Such a sonothrombolysis (STL) treatment requires monitoring and control of MB cavitation to ensure its reproducible efficacy and safety. This paper presents a prototype of a US cavitation imaging system. It is part of an image-guided sonothrombolysis system based on a commercial US scanner and probe (iE33 with S5-1 probe, Philips Healthcare). Backscattered data from insonified MBs is spectrally analyzed to identify the dominant cavitation state: ultraharmonics indicate Stable Cavitation (SC) and broadband noise indicates Inertial Cavitation (IC). Cavitation at lower levels (neither of SC or IC) are classified as Moderate Oscillations (MO). The system is demonstrated in vitro and in vivo. A vessel phantom with Definity microbubbles was imaged through a water path and through a human temporal bone sample. In vivo experiments have also been conducted for imaging cavitation in real time in the brain transcranially in two pigs. Cavitation images have also been obtained and processed offline on 17 pigs of a swine sonothrombolysis study. The lateral resolution of the system is ~1.5mm at 3cm depth, and the axial resolution is 3cm for a 20μs pulse length. The maximum frame rate of the prototype system is 2Hz. Cavitation imaging allows assessing the relative importance of the different cavitation states (MO, SC and IC) in the treatment area inside the skull and their changes as a function of acoustic amplitude. The temporal evolution of cavitation can also be assessed, showing that one 20us pulse destroys the majority of the MBs in the treatment area at MIs higher than 1. Such a thera- y monitoring system will be critical for the reproducible safe and effective administration of STL treatment for acute ischemic stroke.