Crake Calum, Papademetriou Iason T, Zhang Yongzhi, Vykhodtseva Natalia, McDannold Nathan J, Porter Tyrone M
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Mechanical Engineering, Boston University, Boston, Massachusetts, USA.
Ultrasound Med Biol. 2018 Dec;44(12):2609-2624. doi: 10.1016/j.ultrasmedbio.2018.07.023. Epub 2018 Sep 8.
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.
通过聚焦超声（FUS）对实体肿瘤进行热消融是一种非侵入性的、图像引导的传统手术切除替代方法。然而，由于热对流，该技术在血管化器官中的应用受到限制，导致超声处理时间长且热损伤形成不可预测。已发现声空化可增强加热，但需要使用外源性核并进行充分的声学监测。在本研究中，我们采用相移纳米乳剂（PSNE）来促进空化，并在临床MRI扫描仪的孔腔内将被动声学映射（PAM）与传统磁共振成像（MRI）温度测量相结合。在有或没有PSNE以促进空化的情况下，在体内兔肿瘤模型中同时进行PAM和MRI温度测量。使用PAM可以检测到纳米乳剂的汽化和空化，这导致加热加速，并通过MRI温度测量进行监测。从MRI评估的最大加热与积分声发射密切相关，说明了空化增强加热。对组织的检查显示，在存在PSNE的情况下热损伤更大，这与温度测量数据一致。在多只动物的94次超声处理中使用固定的暴露条件，结果显示声发射的平均幅度增加以及由此导致的温度升高，但超声处理之间存在显著差异，进一步说明了实时监测的必要性。结果表明联合使用PAM和MRI监测肿瘤消融的实用性，并为PSNE促进空化增强损伤的能力提供了进一步证据。
