超声作用下双模态造影剂微泡的声空化和热效应

The cavitation and thermal effects induced by dual-modal contrast agent microbubbles activated by ultrasound exposures

为将多模态造影剂微泡更好地应用于精准诊疗领域,研究了磁性双模态造影剂微泡的动态特性。将亲水性超顺磁四氧化三铁磁性纳米颗粒(SPIO)挂载到超声造影剂白蛋白包膜上,构建出超声/核磁共振(US/MRI)双模态造影剂微泡。基于被动空化探测实验和热电偶数据采集实验,系统性地研究了SPIO浓度对双模态造影剂微泡声空化效应和热效应的影响。结果显示:当SPIO浓度保持恒定时,SPIO-albumin微泡的瞬态空化(IC)阈值随着驱动超声脉冲宽度的增加或驱动超声频率更接近微泡共振频率而降低;双模态造影剂微泡产生的瞬态空化剂量(ICD)将随着SPIO颗粒浓度的增加而增大;当驱动声压相同时,与PBS和SPIO溶液相比,包膜材料中含有多SPIO纳米颗粒的SPIO-albumin微泡具有更快的升温速率和更高的峰值温度,这将有利于实现更好的超声热疗效果。

Dual-modal contrast agent microbubbles(MBs),which can integrate both ultrasound(US)and magnetic resonance imaging(MRI)diagnostic/therapeutic functions,have attracted broad interests of researchers.In the present work,super paramagnetic iron oxide nanoparticles(SPIOs)were embedded into albumin-shelled microbubbles to fabricate dual-modal US/MRI contrast agents(named as SPIO-albumin MBs).Then,the dynamic behaviors of SPIO-albumin MBs,especially the impact of SPIO particle concentration on the inertial cavitation(IC)and thermal effects of SPIO-albumin MBs,were studied based passive cavitation detection(PCD)and thermal couple detecting systems.The results showed that:with constant SPIO concentration,constant,the IC threshold of SPIO-albumin MBs was reduced,as the acoustic driving pulse length increased or the acoustic driving frequency became closer to the MB resonance frequency;the IC dose(ICD)of SPIO-albumin MBs was significantly enhanced with the increasing SPIO concentration;and comparing with pure phosphate buffer saline(PBS)and SPIO solutions,the SPIO-albumin MB solution with more SPIOs embedded into the albumin shell demonstrated greater temperature elevation rate and higher maximum temperature enhancement,which could be helpful to achieve better treatment effect of ultrasound thermal therapy.