A SIMPLE METHOD FOR QUANTIFYING ULTRASOUND-TRIGGERED MICROBUBBLE DESTRUCTION
A SIMPLE METHOD FOR QUANTIFYING ULTRASOUND-TRIGGERED MICROBUBBLE DESTRUCTION
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DOI：
10.1016/j.ultrasmedbio.2011.03.005
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发表时间：
2011-06-01
影响因子：
2.9
通讯作者：
Chen, Ran-Chou
中科院分区：
文献类型：
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作者：
Hung, Shuo-Hui;Yeh, Chih-Kuang;Chen, Ran-Chou
超声触发微泡破坏（UTMD）对于靶向药物输送至关重要，但目前对其实时监测尚无商定的黄金标准。本研究使用临床诊断超声扫描仪来量化不同机械指数（MI）值对微泡的破坏效果。这是通过测量外周血管的信号强度来实现的，该信号强度代表全身微泡浓度。本研究使用 24 只雄性 Sprague-Dawley 大鼠和 SonoVue 造影剂，其中 6 只用于测定信号饱和度，18 只用于研究微泡破坏。在实验的第一部分，将四种不同的 SonoVue 剂量（200、400、600 和 800 μL/kg）注射到六只大鼠中，并使用诊断超声扫描仪记录其右股动脉的信号强度。该数据用于绘制时间强度曲线 (TIC)，以确定信号达到饱和的浓度。然后使用 400 μL/kg 剂量进行 UTMD 研究，因为其峰值信号强度 (PSI) 安全地位于强度-浓度曲线的线性部分内。其余 18 只大鼠被分为三个 MI 组（0.2、0.6 和 1.0），对每只大鼠进行以下操作：首先使用来自信号饱和度研究的相同扫描仪进行假暴露的 TIC 记录（无需超声处理）。同时，将另一台超声扫描仪应用于左后肢内收肌，随后进行超声处理。然后，在激活两台超声扫描仪的情况下进行超声处理 TIC 记录。还获得了第二次超声处理的 TIC 记录以进行比较。 TIC 显示，在 MI = 0.6 和 MI = 1.0 组中超声处理后，曲线下面积和增强持续时间减少，但 MI 5 0.2 组则没有减少。 MI 为 0.6 和 1.0 的组中，超声处理后 PSI 略有降低，但没有统计学意义。每组第一次和第二次超声处理之间的 TIC 不存在显着差异。使用源自 TIC 曲线的估计浓度-时间曲线进行药代动力学分析，发现 SonoVue 在 MI = 0.6 和 MI = 1.0 组中具有更快的清除速度和缩短的半衰期。总之，本研究表明，从外周血管测量的超声信号是全身微泡浓度的可行指标，可用于量化目标部位超声触发的微泡破坏。 (E-mail: chenranchou@yahoo.com.tw) (C) 2011 世界超声医学与生物学联合会。
Ultrasound-triggered microbubble destruction (UTMD) is essential for targeted drug delivery but currently there is no agreed gold standard for its real-time monitoring. This study used a clinical diagnostic ultrasound scanner to quantify the destruction effects of different values of mechanical index (MI) on microbubble. This was achieved by measuring the signal intensity of peripheral vessels, which is representative of systemic microbubble concentration. Twenty-four male Sprague-Dawley rats and SonoVue contrast agent were used for this study, six for the determination of signal saturation and 18 for the study of microbubble destruction. In the first part of the experiment, four different SonoVue doses (200, 400, 600 and 800 mu L/kg) were injected into each of six rats and the signal intensity in their right femoral arteries were recorded using a diagnostic ultrasound scanner. This data was used to plot time-intensity curves (TIC) to determine at which concentration the signal reaches saturation. Then UTMD studies were performed using the 400 mu L/kg dose as its peak signal intensity (PSI) was safely within the linear portion of the intensity-concentration curve. The remaining 18 rats were divided into three MI groups (0.2, 0.6 and 1.0) and for each rat, the following was performed: TIC recording of a sham exposure without sonication was performed first using the same scanner from signal saturation study. Simultaneously, another ultrasound scanner was applied to the adductor muscles of left hind limb for sonication later. Then, a sonication TIC recording was performed, with both ultrasound scanners activated. A TIC recording of second sonication was also obtained for comparison. The TICs showed that the area under the curve and the enhancement duration were reduced after sonication in the groups MI = 0.6 and MI = 1.0 but not for the group MI 5 0.2. The PSI in the groups with MI of 0.6 and 1.0 were slightly lowered after sonication, although it is not statistically significant. No significant difference of TIC exists between the first and the second sonication for each group. Pharmacokinetic analysis was performed with estimated concentration-time curve derived from TIC curve and found that SonoVue had faster clearance and decreased half-life in the groups MI = 0.6 and MI = 1.0. In conclusion, this study shows that sonographic signal measured from peripheral vessels is a feasible indicator of systemic microbubble concentration and may be used to quantify ultrasound-triggered microbubble destruction at target site. (E-mail: chenranchou@yahoo.com.tw) (C) 2011 World Federation for Ultrasound in Medicine & Biology.