The uniqueness of IRE stems from its non-thermal and non-pharmacological characteristics. This differs from ethanol injection that utilises chemical agents or radiofrequency ablation or microwave ablation which utilises thermal energy. IRE is the process where electrical pulses of microsecond lengths are used to permanently destabilise the electric potential across the cell membrane, causing permeabilisation of the cell membrane and innumerous nanopores in the lipid bilayers, eventually leading to cell death as a result of inhibition of the resealing of the membrane. In the typical IRE protocol, electrical pulses are generated between two electrodes placed into and onto the outer regions of the specific target lesion.
In contrast to thermal tissue ablation, IRE is truly unique due to its advantage in ablating tissues without being affected by a “heat-sink” effect. One major problem with thermal ablation is the heat sink effect, which describes the ablative thermal heat dissipated by adjacent blood flow. Therefore, thermal ablation on tissues near blood vessels is limited and ineffective since these tissues are exposed to suboptimal thermal energy.
Another significant advantage of IRE is the ability to create a distinct margin separating ablated tissues and normal tissues. We have shown in our preliminary studies that IRE-induced cell death is sharply demarcated from the adjacent normal tissues. In addition to well-marginated ablation, IRE was found to preserve vital structures including vessels and intrahepatic bile ducts. Since the electrical pulses of IRE are produced in milliseconds, IRE requires considerably less time to create complete tissue ablation of a 3cm–diameter lesion in the liver.
Another clinically significant advantage of IRE is its ability to use real-time monitoring of ablation. We have demonstrated for the first time that real-time ultrasound imaging can monitor IRE throughout the procedure from the insertion of probes, to the ablation itself, as well as post-ablation imaging for monitoring immediate complications. In addition, we have shown the feasibility of evaluating the IRE-ablation zone within 72 hours with CT and MRI.
Lastly, several preliminary studies have shown that IRE may create cell death via combination of both necrotic and apoptotic pathways. This finding is of significant value as apoptotic cell death requires less time for healing and recovery. It also creates less fibrotic changes within the ablated zone which also may add functional benefits to the ablated organs.
One of the potential disadvantages of IRE is an arrhythmogenic effect on the heart, particularly the possibility of inducing ventricular fibrillation. For this reason IRE will be utilised in a gated fashion, with the electrical energy delivered during the relaxation phase of the cardiac cycle.
Irreversible electroporation has received a great deal of attention for its potential role in medicine as a non-thermal and non-pharmacological method for tumour ablation. To date multiple non-clinical studies have supported the theoretical advantages this technology offers. Currently early human studies are proving the overall safety of this technique. Multiple large studies are in the pipeline to prove clinical efficacy.
Stephen T Kee is associate professor of Radiology and section chief, Interventional Radiology, David Geffen School of Medicine at UCLA, Los Angeles, USA.
