Simultaneous Passive Acoustic Mapping and Magnetic Resonance Thermometry for Monitoring of Cavitation-Enhanced Tumor Ablation in Rabbits Using Focused Ultrasound and Phase-Shift Nanoemulsions

Abstract

Thermal ablation of solid tumors via focused ultrasound (FUS) is a non-invasive image-guided alternative to conventional surgical resection. However, the usefulness of the technique is limited in vascularized organs because of convection of heat, resulting in long sonication times and unpredictable thermal lesion formation. Acoustic cavitation has been found to enhance heating but requires use of exogenous nuclei and sufficient acoustic monitoring. In this study, we employed phase-shift nanoemulsions (PSNEs) to promote cavitation and incorporated passive acoustic mapping (PAM) alongside conventional magnetic resonance imaging (MRI) thermometry within the bore of a clinical MRI scanner. Simultaneous PAM and MRI thermometry were performed in an in vivo rabbit tumor model, with and without PSNE to promote cavitation. Vaporization and cavitation of the nanoemulsion could be detected using PAM, which led to accelerated heating, monitored with MRI thermometry. The maximum heating assessed from MRI was well correlated with the integrated acoustic emissions, illustrating cavitation-enhanced heating. Examination of tissue revealed thermal lesions that were larger in the presence of PSNE, in agreement with the thermometry data. Using fixed exposure conditions over 94 sonications in multiple animals revealed an increase in the mean amplitude of acoustic emissions and resulting temperature rise, but with significant variability between sonications, further illustrating the need for real-time monitoring. The results indicate the utility of combined PAM and MRI for monitoring of tumor ablation and provide further evidence for the ability of PSNEs to promote cavitation-enhanced lesioning.