脉冲高强度聚焦超声在体外模型中增强溶栓作用。
Pulsed high-intensity focused ultrasound enhances thrombolysis in an in vitro model.
作者信息
Frenkel Victor, Oberoi Jay, Stone Michael J, Park Melissa, Deng Cheri, Wood Bradford J, Neeman Ziv, Horne McDonald, Li King C P
机构信息
Departments of Diagnostic Radiology and Laboratory Medicine, Clinical Center, National Institutes of Health, 10 Center Drive, Bldg 10, Room 1C657, Bethesda, MD 20892, USA.
出版信息
Radiology. 2006 Apr;239(1):86-93. doi: 10.1148/radiol.2391042181. Epub 2006 Feb 21.
PURPOSE
To evaluate the use of pulsed high-intensity focused ultrasound exposures to improve tissue plasminogen activator (tPA)-mediated thrombolysis in an in vitro model.
MATERIALS AND METHODS
All experimental work was compliant with institutional guidelines and HIPAA. Clots were formed by placing 1 mL of human blood in closed-off sections of pediatric Penrose tubes. Four experimental groups were evaluated: control (nontreated) clots, clots treated with pulsed high-intensity focused ultrasound only, clots treated with tPA only, and clots treated with pulsed high-intensity focused ultrasound plus tPA. The focused ultrasound exposures (real or sham) were followed by incubations of the clots in tPA with saline or in saline only. Thrombolysis was measured as the relative reduction in the mass of the clot. D-Dimer assays also were performed. Two additional experiments were performed and yielded dose-response curves for two exposure parameters: number of pulses per raster point and total acoustic power. Radiation force-induced displacements caused by focused ultrasound exposures were simulated in the clots. A Tukey-Kramer honestly significant difference test was performed for comparisons between all pairs of experimental groups.
RESULTS
The clots treated with focused ultrasound alone did not show significant increases in thrombolysis compared with the control clots. The clots treated with focused ultrasound plus tPA showed a 50% ([30.2/20.1]/20.1) increase in the degree of thrombolysis compared with the clots treated with tPA only (P < .001), further corroborating the d-dimer assay results (P < .001). Additional experiments revealed how increasing both the number of pulses per raster point and the total acoustic power yielded corresponding increases in the thrombolysis rate. In the latter experiment, simulations performed at a range of power settings revealed a direct correlation between increased displacement and observed thrombolysis rate.
CONCLUSION
The rate of tPA-mediated thrombolysis can be enhanced by using pulsed high-intensity focused ultrasound exposure in vitro.
目的
在体外模型中评估使用脉冲高强度聚焦超声照射以改善组织型纤溶酶原激活剂（tPA）介导的溶栓作用。
材料与方法
所有实验工作均符合机构指南和《健康保险流通与责任法案》（HIPAA）。通过将1 mL人血置于小儿Penrose管的封闭段来形成血凝块。评估了四个实验组：对照（未处理）血凝块、仅用脉冲高强度聚焦超声处理的血凝块、仅用tPA处理的血凝块以及用脉冲高强度聚焦超声加tPA处理的血凝块。聚焦超声照射（真实或假照射）后，将血凝块在含tPA的盐溶液中或仅在盐溶液中孵育。溶栓以血凝块质量的相对减少来衡量。还进行了D - 二聚体检测。进行了另外两个实验，并得出了两个照射参数的剂量 - 反应曲线：每个光栅点的脉冲数和总声功率。模拟了聚焦超声照射在血凝块中引起的辐射力诱导位移。对所有实验组对之间进行比较时进行了Tukey - Kramer真实显著性差异检验。
结果
与对照血凝块相比，仅用聚焦超声处理的血凝块溶栓未显示出显著增加。与仅用tPA处理的血凝块相比，用聚焦超声加tPA处理的血凝块溶栓程度增加了50%（[30.2/20.1]/20.1）（P <.001），进一步证实了D - 二聚体检测结果（P <.001）。另外的实验揭示了增加每个光栅点的脉冲数和总声功率如何相应地提高溶栓率。在后者的实验中，在一系列功率设置下进行的模拟显示位移增加与观察到的溶栓率之间存在直接相关性。
结论
在体外使用脉冲高强度聚焦超声照射可提高tPA介导的溶栓率。
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