高压超短脉冲电场消融:一种微创治疗的新范式

High voltage ultrashort electric field ablation:A novel paradigm for minimally invasive therapy

微创外科代表了外科学发展的新趋势,其中,将能量传递到病灶、控制局部温度来完成治疗的“热消融”疗法,已经被推荐为多种直径<5 cm的实体瘤的根治性疗法之一。对于位置靠近血管等重要结构、临床上不适合手术治疗的肿瘤,也难以施行“热消融”治疗。基于“高压超短脉冲电场”的细胞生物学效应开发的新一代微创治疗技术,能够在根除癌灶的同时避免损伤病灶周围功能性管道结构,弥补了“热消融”疗法的不足。如果展开多学科研究继续发展这项技术,这种“非热消融”疗法将成为微创消融技术的新范式。而“高压超短脉冲电场”致死细胞的生物物理学原理是这种多学科合作研究的基础。本文先回顾了“诱导跨膜电位”假说的发展历史。然后从热力学的原理出发,介绍我们最近提出的这类疗法的生物物理学机制“等效力场”假说:细胞外电场可以被等效地看成作用于细胞膜上带电粒子的力场。电场力是远距离作用力,在脉冲作用过程中对电场内带电粒子加速。这些粒子在没有受到源于分子间相互作用的阻力之前,超短高强度的电场就能够让它们获得导致细胞膜结构变化的平动速度,脉冲电场的作用范围与这种平动速度升高呈正相关。平动动能(与平动速度的平方呈正相关)也属于“热”的一部分,但它不是消融疗效的控制因素。从理论源头理解这种新消融方法,有助于这种微创消融新技术的范式转换。

Minimally invasive surgery represents a new trend in the development of surgery,in which the"thermal ablation"that control the local temperature to complete the treatment by delivering energy to the lesion had been recommended as one of the radical therapies for various solid tumors less than 5cm in diameter.Tumors locating close to important structures such as blood vessels,which are not suitable for surgery clinically,are also difficult to perform"thermal ablation"treatment.The novel minimally invasive treatment technology developed based on the cellular biological effects of"high voltage ultrashort pulsed electric field"can eradicate cancer while sparing the functional ducts around the lesion,and make up for the deficiency of"thermal ablation"therapy.This"non-thermal ablation"therapy will be a new paradigm of minimally invasive ablation technology that need to be achieved through multidisciplinary collaborative research.The biophysical principle of cell-destructing by"high-voltage ultrashort pulsed electric fields"is the basis for this collaborative research.The development of the"induced transmembrane potential"hypothesis had been reviewed here.Then,starting from the principles of thermodynamics,the biophysical mechanism of this novel modality that we recently proposed-“the equivalent force field"hypothesis had been introduced:the extracellular electric field can be equivalently viewed as a force field acting on charged particles on the plasma membrane.Electric field force is a long-distance force that accelerate charged particles inside of the electric field.Before experiencing resistance from intermolecular interactions,the charged particle had been accelerated by the ultrashort high-intensity electric field,which can deform and destruct the membrane structure using the translational velocities gained during pulsing.The ablation of the pulsed electric field is positively correlated with this translational velocity increase.The translational kinetic energy(positively related to the square of the translational velocity)is also part of the"heat",but it is not a determinant of ablation efficacy.Understanding this new ablation method theoretically is helpful for the paradigm shift of the novel minimally invasive ablation techniques.