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.

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications

“…Crake et al used combined passive acoustic mapping and magnetic resonance thermometry for monitoring US-mediated cavitation-enhanced tumor ablation via NEs. This study also provided further evidence for the ability of phase-shifting NEs to promote cavitation-enhanced lesion formation [ 346 ]. The phase change threshold is dependent on US frequency, pulse duration, and droplet temperature [ 130 ].…”

Diffuse Midline Gliomas: Challenges and New Strategies in a Changing Clinical Landscape

“…The second role of focused ultrasound is targeting tumor foci. Its use has been proposed for deep nodules that pose a therapeutic challenge for both open surgical intervention and laser interstitial thermal therapy (LITT), similar to what has been achieved in movement disorders [ 65 ]; thus far, however, its use remains experimental, even though numerous animal studies are emerging, showing the feasibility of such a technique [ 66 , 67 , 68 , 69 ].…”

Contactless Thermometry by MRI and MRS: Advanced Methods for Thermotherapy and Biomaterials

“…In particular, the usefulness of hyperthermia may be limited by heat convection in highly vascularized tumors. This results in long sonication times and unpredictable thermal-lesion formation in FUS (Crake et al, 2018(Crake et al, , 2017. Therefore, FUS has been shown to be more efficient when used in conjunction with phase-shift nanoemulsions (PSNE).…”

“…This is achieved by a FUS transducer through (1) a high-amplitude burst producing evaporation, followed by (2) a low-amplitude burst to promote cavitation and temperature rise. Crake et al have evaluated a combination of MRT (phase-based PRFS) and passive acoustic mapping (PAM, by way of a separate US array) for monitoring the effects of PSNE-enhanced FUS through phantom studies (Crake et al, 2017) and tumor ablation experiments in rabbits (Crake et al, 2018). The use of PAM and MRI together allowed simultaneous mapping of cavitation and the resulting temperature rise, respectively.…”