Irreversible electroporation attenuates neointimal formation after angioplasty

Restenosis following coronary angioplasty represents a major clinical problem. Irreversible electroporation (IRE) is a nonthermal, nonpharmacological cell ablation method. IRE utilizes a sequence of electrical pulses that produce permanent damage to tissue within a few seconds. Methods and results: The left carotid arteries of eight rats underwent in vivo intimal damage using two Fogarty angioplasty catheters. The procedure was immediately followed by IRE ablation in four rats, while the remaining four were used as the control group. The IRE ablation was performed using a sequence of ten dc pulses of 3800 V/cm, 100 $mu$s each, at a frequency of ten pulses per second, applied across the blood vessel between two parallel electrodes. The electrical conductance of the treated tissue was measured during the electroporation to provide real-time feedback of the process. Left carotid arteries were excised and fixated after a 28-day follow-up period. Neointimal formation was evaluated histologically. The use of IRE was successful in three out of four animals in a way that is consistent with the measurements of blood vessel electrical properties. The integrity of the endothelial layer was recovered in the IRE-treated animals, compared with control. Successful IRE reduced neointima to media ratio ($0.57 pm 0.4$ versus $1.88 pm 1.0, P= 0.02$). Conclusions: We report for the first time the in vivo results of attenuation of neointimal formation using IRE. Our study shows that IRE might be able to attenuate neointimal formation after angioplasty damage in a rodent model of restenosis. This approach may open new venues in the treatment of coronary artery restenosis after balloon angioplasty.      

Electrode activation sequencing employing conductivity changes in irreversible electroporation tissue ablation

Irreversible electroporation (IRE) uses high-voltage pulses applied to tissue, which cause dielectric breakdown of cell membranes resulting in cell death. IRE is a promising technique for ablation of nonresectable tumors because it can be configured to spare critical structures such as blood vessels. A consequence of pulse application is an increase in tissue electrical conductivity due to current pathways being opened in cell membranes. We propose a novel IRE method introducing electrode switching and pulse sequencing in which tissue conductivity is first increased using preparatory pulses in order to form high-conductivity zones, which then helps provide higher electric field intensity within the targeted tissue as subsequent pulses are applied, and hence, enhances the efficiency and selectivity of the IRE treatment. We demonstrate the potential of this method using computational models on simple geometries.     

Experimental characterization and numerical modeling of tissue electrical conductivity during pulsed electric fields for irreversible electroporation treatment planning

Irreversible electroporation is a new technique to kill cells in targeted tissue, such as tumors, through a nonthermal mechanism using electric pulses to irrecoverably disrupt the cell membrane. Treatment effects relate to the tissue electric field distribution, which can be predicted with numerical modeling for therapy planning. Pulse effects will change the cell and tissue properties through thermal and electroporation (EP)-based processes. This investigation characterizes these changes by measuring the electrical conductivity and temperature of ex vivo renal porcine tissue within a single pulse and for a 200 pulse protocol. These changes are incorporated into an equivalent circuit model for cells and tissue with a variable EP-based resistance, providing a potential method to estimate conductivity as a function of electric field and pulse length for other tissues. Finally, a numerical model using a human kidney volumetric mesh evaluated how treatment predictions vary when EP- and temperature-based electrical conductivity changes are incorporated. We conclude that significant changes in predicted outcomes will occur when the experimental results are applied to the numerical model, where the direction and degree of change varies with the electric field considered.     

Subnanosecond electric pulses cause membrane permeabilization and cell death

Subnanosecond electric pulses (200 ps) at electric field intensities on the order of 20 kV/cm cause the death of B16.F10 murine melanoma cells when applied for minutes with a pulse repetition rate of 10 kHz. The lethal effect of the ultrashort pulses is found to be caused by a combination of thermal effects and electrical effects. Studies on the cellular level show increased transport across the membrane at much lower exposure times or number of pulses. Exposed to 2000 pulses, NG108 cells exhibit an increase in membrane conductance, but only allow transmembrane currents to flow, if the medium is positively biased with respect to the cell interior. This means that the cell membrane behaves like a rectifying diode. This increase in membrane conductance is a nonthermal process, since the temperature rise due to the pulsing is negligible.     

长脉冲致硅基 QPD损伤面积及形貌实验研究

为了研究硅基QPD在不同能量密度、不同脉宽激光辐照下的损伤面积、形貌,基于二维显微测量技术,测量了硅基QPD单一象限的损伤面积、形貌随激光能量密度和脉宽的变化。结果表明,在毫秒脉冲激光作用下,硅基QPD产生表面剥落、褶皱、裂纹、熔坑等损伤效果,且主要受入射激光功率密度影响,损伤面积随激光能量密度逐渐增加,随脉宽增加逐渐降低。通过实测分析,得出了不同激光脉宽下,硅基QPD表面形貌损伤阈值。激光脉宽为0.5 ms,能量密度为15.79 J/cm2时,硅基QPD出现熔融损伤;而脉宽为1.0、1.5、2.0、3.0 ms时,硅基QPD出现表面剥落的能量密度值为14.12、33.94、39.76、47.62 J/cm2。     

The course of tissue permeabilization studied on a mathematical model of a subcutaneous tumor in small animals

One of the ways to potentiate antitumor effectiveness of chemotherapeutic drugs is by local application of short intense electric pulses. This causes an increase of the cell membrane permeability and is called electropermeabilization. In order to study the course of tissue permeabilization of a subcutaneous tumor in small animals, a mathematical model was built with the commercial program EMAS, which uses the finite element method. The model is based on the tissue specific conductivity values found in literature, experimentally determined electric field threshold values of reversible and irreversible tissue permeabilization, and conductivity changes in the tissues. The results obtained with the model were then compared to experimental results from the treatment of subcutaneous tumors in mice and a good agreement was obtained. Our results and the reversible and irreversible thresholds used coincide well with the effectiveness of the electrochemotherapy in real tumors where experiments show antitumor effectiveness for amplitudes higher than 900 V/cm ratio and pronounced antitumor effects at 1300 V/cm ratio.     

不同离焦条件对骨硬组织激光消融的影响

评估了不同离焦辐照条件对脉冲CO2激光骨硬组织消融的影响。实验样品为新鲜离体牛胫骨组织,置于由计算机自动控制的一维电动平移台上。调节工作距离,分别在光束聚焦平面前后光斑尺寸约为510μm处进行非接触式垂直照射。脉冲CO2激光波长为10.64μm,脉冲频率为60 Hz,能量密度范围5~45 J/cm2。平移台移动速度为20 mm/s,重复扫描6次。肉眼和显微镜观察组织样品形态学变化,常规组织病理切片处理,苏木精-伊红(HE)染色,共焦扫描显微镜观察并摄取图像。运用测量软件测量骨样品消融凹陷的几何尺寸,获得切口宽度、深度和切口截面积随辐射曝光量的变化关系。结果表明,脉冲CO2激光可以应用于骨头等硬组织的切割,不同的离焦辐照条件对组织消融效果具有重要影响;在临床上,为获得窄且深的消融切口和高的消融率,可以稍微将光束聚焦在组织表面下方。     

The effect of CO2 laser pulse repetition rate on tissueablation rate and thermal damage

The ablation rate and thermal damage in skin produced by a superpulsed CO2 laser operating at pulse repetition rates between 1 and 900 Hz was measured. When delivering a fixed number of pulses (20 or 30) of equal energy, a 55-60% increase in the amount of tissue ablated was observed when the pulse repetition rate rose from 10 to 200 Hz. At pulse repetition rates greater than 200 Hz no further increase was seen. Under identical conditions, an 80% increase in the zone of thermal damage was observed when the pulse repetition rate was increased from 1 to 60 Hz. The large increases in tissue ablation and tissue damage may indicate the existence of a layer of mixed-phase (i.e., liquid and vapor) or metastable liquid which can store significant amounts of thermal energy between pulses. The data suggest that CO2 lasers should be operated at relatively low repetition rates for optimal performance.     

TEA CO_2激光光电转换效应研究

用TEA CO_2激光脉冲聚焦在真空池中的金属靶上,激光产生等离子体的反向喷射会在器壁和金属靶之间产生电压脉冲.实验研究了光束聚焦情况和真空度对光电转换效应的影响.当峰值功率密度为1.4×10~9瓦/厘米~2时,最大脉冲输出电压为300伏,总体效率为0.01%.采用二个分离的收集极可以测量等离子体的膨胀速度.     

激光气化生物组织的试验研究

激光气化生物组织是激光医学应用中的重要方面。探索激光参数对气化效率的影响是激光生物医学的重要研究内容。本文实验研究了532nm、1064nm和1320nm脉冲激光气化离体猪肝脏组织的试验效应,对比三种激光在不同频率、不同脉宽下的气化深度和热损伤深度,结果表明:在气化含血组织中,脉冲532nm脉冲激光的气化效率最高,热损伤区域最小。     

Weak electric fields affect plant development

High-strength electric currents and fields can alter plant physiology by the production of heat within the plant tissue and by the ionization of air molecules at the plant tips. It has been suggested that weak low-frequency electric and magnetic filelds may alter germination and early plant development [4], [5], but the question has not been resolved. Our aim was to determine the possible existence of weak electric-field effects on sunflower germination and to calculate the electric-field threshold inside the seed for any such effects. We found that an applied electric field of 5 kV/m, 60 Hz, produced an internal electric field of 7.5 ×10-4 V/m in a seed in moist soil and resulted in a statistically significant decrease of about 5 percent in germination rate. No effect was found for an applied field of 1 kV/m (1.5 ×10-4 V/m inside the seed). These results established for the first time that electric fields can affect plants by a nonthermal mechanism other than air ionization.     

渍制钪酸盐钡钨阴极脉冲性能的研究

本文对渍制钪酸盐钡钨阴极的脉冲性能作了下述几方面的研究。(1)脉冲发射水平和逸出功分布;(2)脉冲运用下的电子初速分布;(3)脉冲工作比效应;(4)强场下的非常肖特基效应。 本阴极在Tk=850℃下能提供的脉冲发射电流密度大于20A/cm2;平均逸出功=1.7eV;发射的不均匀性与国外报道的M型阴极的相近;在脉冲运用下,电子速度的分散值低于氧化物阴极的。本阴极在场强高于1104V/cm时,出现非常肖特基效应,本文用S值来表征。本阴极的S值明显高于渍制铝酸盐钡钨阴极和L阴极的。造成非常肖特基效应的主要原因是表面逸出功不均匀。在脉冲工作比f=510-3410-2范围内,支取8.8A/cm2时,本阴极有良好的平坦f特性,所以适用于长脉冲、大功率毫米波器件。 最后结合国内外对这种阴极的表面分析结果,对本文的实验结果进行了讨论,这些讨论有助于阐明本阴极的发射机制。     

飞秒激光作用下薄膜的阈值损伤到膜层剥落

在飞秒单脉冲激光损伤HfO_2/SiO_2薄膜样品实验中,随着激光能量密度升高,膜层从缺陷导致的点损伤发展到整层剥落,损伤区域轮廓由模糊变清晰.研究表明,尺度在纳米量级的颗粒缺陷会产生局部的场增强效应,该效应与薄膜干涉场叠加,造成了阈值损伤阶段损伤区域出现大量损伤点,且由于飞秒激光对包括缺陷在内的薄膜材料的本征损伤特性,使其损伤行为较为确定,随着激光能量的提升,薄膜出现更大面积的规则烧蚀区,此时干涉场的作用上升到主导地位,膜层的整层剥落行为掩盖了缺陷的诱导作用.     

An Optimal Sliding Choke Antenna for Hepatic Microwave Ablation

Microwave ablation (MWA) is a minimally invasive technique increasingly used for thermal therapy of liver tumors. Effective MWA requires efficient interstitial antennas that destroy tumors and a margin of healthy tissue, in situ, while minimizing damage to the rest of the organ. Previously, we presented a method for optimizing MWA antenna designs by coupling finite element method models of antennas with a real-coded, multiobjective genetic algorithm. We utilized this procedure to optimize the design of a minimally invasive choke antenna that can be used to create near-spherical ablation zones of adjustable size (radius 1-2 cm) by adjusting treatment durations and a sliding structure of the antenna. Computational results were validated with experiments in ex vivo bovine liver. The optimization procedure yielded antennas with reflection coefficients below -30 dB, which were capable of creating spherical ablation zones up to 2 cm in radius using 100 W input power at 2.45 GHz with treatment durations under 2 min.     

不同场强分布的1064nm激光减反膜损伤特性

设计了两种具有不同场强分布的1 064nm减反射膜结构,即G/H3L/A和G/M2HL/A。采用离子束辅助沉积技术,在K9基底上制备了薄膜,并对薄膜在强激光下的损伤斑形貌及损伤阈值(LIDT)进行了测量。研究结果表明:薄膜的场强分布不同,其抗强激光的能力也不相同。当两种膜系的电场强度(归一化电场强度平方)在薄膜-空气界面处分别为1.039和0.906时,对不同的激光能量(180,150和120mJ),样品G/H3L/A的表面破损斑尺寸均大于样品G/M2HL/A;两种薄膜的激光损伤阈值分别为12.3J/cm2和14.8J/cm2(激光波长为1 064nm,12ns)。这说明,较小的薄膜-空气界面电场强度,有利于激光损伤能力的提高。因此,对于减反射薄膜,在膜系设计时,采用合理的场强分布,降低薄膜-空气界面的电场强度,可以有效改善薄膜的激光损伤特性。     

准分子激光消融兔前列腺的实验研究

报道了使用ＸｅＣｌ准分子激光（３０８ｎｍ）照射兔前列腺标本。观察了在不同频率、不同介质等条件下对离体免前列腺组织的消融效果，测得损伤阈值为４００ｍＪ／ｃｍ２。结果表明，准分子激光具有消融效果高、对周围组织损伤轻、损伤范围易于控制等特点，具有实际临床应用的价值。     

Ultrafast Near‐Infrared Light‐Triggered Intracellular Uncaging to Probe Cell Signaling

The possibility of regulating cell signaling with high spatial and temporal resolution within individual cells and complex cellular networks has important implications in biomedicine. This article demonstrates a general strategy that uses near‐infrared tissue‐penetrating laser pulses to uncage biomolecules from plasmonic gold‐coated liposomes, i.e., plasmonic liposomes, to activate cell signaling in a nonthermal, ultrafast, and highly controllable fashion. Near‐infrared picosecond laser pulse induces transient nanobubbles around plasmonic liposomes. The mechanical force generated from the collapse of nanobubbles rapidly ejects encapsulated compound within 0.1 ms. This article shows that single pulse irradiation triggers the rapid intracellular uncaging of calcein from plasmonic liposomes inside endolysosomes. The uncaged calcein then evenly distributes over the entire cytosol and nucleus. Furthermore, this article demonstrates the ability to trigger calcium signaling in both an immortalized cell line and primary dorsal root ganglion neurons by intracellular uncaging of inositol triphosphate (IP₃), an endogenous cell calcium signaling second messenger. Compared with other uncaging techniques, this ultrafast near‐infrared light‐driven molecular uncaging method is easily adaptable to deliver a wide range of bioactive molecules with an ultrafast optical switch, enabling new possibilities to investigate signaling pathways within individual cells and cellular networks.     

不同脉宽皮秒激光对介质膜损伤修复的热影响

为了更深层次探究超短脉冲激光对惯性约束聚变(ICF)光学系统中常见的多膜层元件损伤修复性能以及特点,分别采用了240、35、6ps的1053nm激光脉冲在1053nm 0°高反膜上进行了损伤修复以及损伤增长测试实验,并在1053nm 45°高反膜上进行了大损伤区域的扫描修复实验。通过比较不同脉宽的修复点形貌以及损伤增长阈值,说明了超短脉冲用于修复多膜层光学元件损伤的优越性,并且脉宽越短修复效果越好。多点脉冲扫描修复结果表明,可以通过三维控制系统来任意控制扫描修复点形貌以达到最佳修复状态。     

193nm准分子激光光解切除皮肤切除深度与照射剂量的研究

八十年代初,随着准分子激光器研制的发展,各国学者从193nm准分子激光能精确蚀刻多聚化合物得到启发,开始研究此波长激光与生物组织的相互作用。Srinvasan与Lane分别用皮肤、肌肉、牙齿、角膜等生物样品试验,发现光量子为6.4eV的紫外激光与生物组织作用时,主要是光化学作用(Photochemical mechanism),受照区域周围热损伤轻微。深入的研究表明:适当控制激光的各种物理参数(脉冲重复频率、单脉冲的能量及照射时间),就可对生物样品进行光分解(Photodecomposition)及光解切除(Photoablation)。七十年代以     

Nd:YAG激光辐照牙齿的光热作用理论研究

激光辐照牙齿时所产生的温升容易引起牙髓细胞不可逆的损伤,导致牙髓细胞坏死,因此必须对相关的激光参数加以控制.建立了激光与牙齿相互作用的热传输模型,利用Crank-Nicolson有限差分法数值模拟了不同Nd:YAG激光参数照射下牙齿表面及内部的温度场的分布.计算结果表明,激光脉冲的宽度、间隔、个数决定了牙齿表面和牙髓腔壁的最终温度,将激光的总能量分配到几个脉冲之中,导致了牙齿表面温度的降低;而在牙髓腔壁出现了相反的情况,即脉冲数越多,牙齿内壁的温度也就越高.对相关的光热机理进行了探讨,提出控制单脉冲能量是光热蚀除牙齿应采用的最佳措施.