IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Apr;68(4):961-968. doi: 10.1109/TUFFC.2020.3026697. Epub 2021 Mar 26.
Focused ultrasound (FUS) exposure of micro-bubble (MB) contrast agents can transiently increase microvascular permeability allowing anticancer drugs to extravasate into a targeted tumor tissue. Either fixed or mechanically steered in space, most studies to date have used a single element focused transducer to deliver the ultrasound (US) energy. The goal of this study was to investigate various multi-FUS strategies implemented on a programmable US scanner (Vantage 256, Verasonics Inc.) equipped with a linear array for image guidance and a 128-element therapy transducer (HIFUPlex-06, Sonic Concepts). The multi-FUS strategies include multi-FUS with sequential excitation (multi-FUS-SE) and multi-FUS with temporal sequential excitation (multi-FUS-TSE) and were compared to single-FUS and sham treatment. This study was performed using athymic mice implanted with breast cancer cells ( N = 20 ). FUS therapy experiments were performed for 10 min after a solution containing MBs (Definity, Lantheus Medical Imaging Inc.) and near-infrared (NIR, surrogate drug) dye were injected via the tail vein. The fluorescent signal was monitored using an in vivo optical imaging system (Pearl Trilogy, LI-COR) to quantify intratumoral dye accumulation at baseline and again at 0.1, 24, and 48 h after receiving US therapy. Animals were then euthanized for ex vivo dye extraction analysis. At 48 h, fluorescent tracer accumulation within the tumor space for the multi-FUS-TSE therapy group animals was found to be 67.3%, 50.3%, and 36.2% higher when compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. Also, dye extraction and fluorescence measurements from excised tumor tissue found increases of 243.2%, 163.1%, and 68.1% for the multi-FUS-TSE group compared to sham, single-FUS, and multi-FUS-SE therapy group measures, respectively. In summary, experimental results revealed that for a multi-FUS sequence, increased microvascular permeability was considerably influenced by both the spatial and temporal aspects of the applied US therapy.
聚焦超声（FUS）暴露于微泡（MB）造影剂可以短暂增加微血管通透性，使抗癌药物渗出到靶向肿瘤组织中。迄今为止，大多数研究都使用固定或机械空间导向的单个元件聚焦换能器来输送超声（US）能量。本研究的目的是研究在配备用于图像引导的线性阵列和 128 元件治疗换能器（HIFUPlex-06，Sonic Concepts）的可编程 US 扫描仪（Vantage 256，Verasonics Inc.）上实施的各种多 FUS 策略。多 FUS 策略包括顺序激发的多 FUS（multi-FUS-SE）和时间顺序激发的多 FUS（multi-FUS-TSE），并与单 FUS 和假处理进行了比较。这项研究是在植入乳腺癌细胞的无胸腺小鼠（N=20）中进行的。在通过尾静脉注射包含 MB（Definity，Lantheus Medical Imaging Inc.）和近红外（NIR，替代药物）染料的溶液后，进行 10 分钟的 FUS 治疗实验。使用体内光学成像系统（Pearl Trilogy，LI-COR）监测荧光信号，以量化基线时和接受 US 治疗后 0.1、24 和 48 小时时肿瘤内染料的积累。然后，对动物进行安乐死以进行离体染料提取分析。在 48 小时时，与假处理、单 FUS 和 multi-FUS-SE 治疗组相比，multi-FUS-TSE 治疗组动物的肿瘤内荧光示踪剂积累分别高 67.3%、50.3%和 36.2%。此外，从切除的肿瘤组织中提取的染料和荧光测量值表明，与 sham、single-FUS 和 multi-FUS-SE 治疗组相比，multi-FUS-TSE 组分别增加了 243.2%、163.1%和 68.1%。总之，实验结果表明，对于多 FUS 序列，微血管通透性的增加受到施加的 US 治疗的空间和时间方面的显著影响。
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