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不可逆电穿孔消融:四电极阵列在活体猪肝中创建大容量消融区。

Irreversible electroporation ablation: creation of large-volume ablation zones in in vivo porcine liver with four-electrode arrays.

机构信息

From the Departments of Radiology (L.A., E.B., Y.N., J.S., S.N.G.) and Surgery (M.F.), Hadassah Hebrew University Medical Center, Jerusalem, Israel 91120; and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (S.N.G.).

出版信息

Radiology. 2014 Feb;270(2):416-24. doi: 10.1148/radiol.13130349. Epub 2013 Oct 28.

Abstract

PURPOSE

To prospectively determine optimal parameters with which to achieve defined large target zones of coagulation by using irreversible electroporation (IRE) with four-electrode arrays and the time needed to achieve this treatment effect in an in vivo animal model.

MATERIALS AND METHODS

This study was approved by the animal care and use committee. Ultrasonography (US)-guided IRE ablation (n = 90) was performed in vivo in 69 pig livers with an array of four electrodes (18 gauge) and an electroporation generator. Cardiac-gated 100-µsec IRE pulses were applied sequentially between the six sets of electrode pairs at 2250-3000 V. Multiple algorithms of energy deposition and electrode configuration were studied, including interelectrode spacing (1.5-2.5 cm), number of IRE pulses applied consecutively to each electrode pair (10, 20, 50, and 100), and number of times per cycle each electrode pair was activated (one to 10). Resultant zones of treatment were measured with US 1.5-3 hours after IRE and confirmed at gross and histopathologic examination. Data and ablation times were compared to determine the optimal algorithms with which to achieve 4-7-cm areas of treatment effect in the shortest time possible. In addition, the IRE current applied was correlated with ablation size. Data were analyzed by using analysis of variance with multiple comparisons, t tests, or nonparametric statistics.

RESULTS

For 2.5-cm spacing, ablation diameter was increased by increasing either the overall time of energy application or the number of cycles of 20 pulses (P < .01 for both). IRE application of less than four cycles (or continuous IRE application of 100 pulses) did not result in contiguous ablation. However, sequentially increasing the number of cycles of IRE from four to 10 increased both the electrical current applied (from 14.4 A ± 0.4 to 17.6 A ± 0.7, P = .0004) and ablation diameter (from 5.6 cm ± 0.3 to 6.6 cm ± 0.3, P = .001). Although division of application into cycles did not alter coagulation at 2.0- and 1.5-cm spacing, application of energy to diagonal electrode pairs increased coagulation. Thus, one 100-pulse cycle (11.0 minutes ± 1.4) produced 4.8 cm ± 0.3 of ablation for 2.0-cm spacing with diagonal pairs but only 4.1 cm ± 0.3 of ablation without diagonal pairs (7.5 minutes ± 1.0, P < .03 for both).

CONCLUSION

With four-electrode arrays, IRE can create large contiguous zones of treatment effect in clinically acceptable ablation times; parameters can be tailored to achieve a wide range of ablation sizes. Cyclical deposition of IRE application is beneficial, particularly for larger interprobe spacing, most likely owing to alterations of electrical conductivity that occur after successive applications of IRE energy.

摘要

目的

使用四电极阵列的不可逆电穿孔 (IRE) 来前瞻性地确定实现定义的大目标区域的最佳参数,并确定在体内动物模型中实现这种治疗效果所需的时间。

材料和方法

本研究得到了动物护理和使用委员会的批准。在 69 个猪肝脏中进行了超声引导的 IRE 消融(n=90),使用了四个电极(18 号)和电穿孔发生器的阵列。心脏门控 100-µsec IRE 脉冲以 2250-3000 V 的电压顺序施加到六个电极对之间。研究了多种能量沉积和电极配置算法,包括电极之间的间隔(1.5-2.5 厘米)、连续施加到每个电极对的 IRE 脉冲数(10、20、50 和 100)以及每个电极对在每个循环中激活的次数(1 到 10)。IRE 后 1.5-3 小时用 US 测量治疗后的区域,并在大体和组织病理学检查中确认。比较数据和消融时间,以确定在最短时间内实现 4-7cm 治疗效果的最佳算法。此外,还分析了 IRE 电流与消融大小的相关性。通过方差分析、t 检验或非参数统计分析对数据进行分析。

结果

对于 2.5 厘米的间隔,通过增加能量应用的总时间或增加 20 脉冲的循环次数(两者均 P<.01),消融直径增加。IRE 应用少于四个循环(或连续 IRE 应用 100 个脉冲)不会导致连续消融。然而,连续增加 IRE 循环的次数从四个循环增加到十个循环,既增加了施加的电流(从 14.4A±0.4 增加到 17.6A±0.7,P=0.0004),又增加了消融直径(从 5.6cm±0.3 增加到 6.6cm±0.3,P=0.001)。虽然将应用分为循环不会改变 2.0 和 1.5 厘米间隔处的凝血,但对角电极对的能量应用会增加凝血。因此,一个 100 脉冲循环(11.0 分钟±1.4)在 2.0 厘米的间隔处对角对产生 4.8cm±0.3 的消融,但在没有对角对的情况下仅产生 4.1cm±0.3 的消融(7.5 分钟±1.0,两者均 P<.03)。

结论

使用四电极阵列,IRE 可以在可接受的消融时间内创建大的连续治疗区域;可以根据需要调整参数以实现广泛的消融大小。IRE 应用的循环沉积是有益的,特别是对于较大的探头间隔,这可能是由于连续应用 IRE 能量后电导率的变化。

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