Selective Electroporation of Liver Tumor Nodules by Means of Hypersaline Infusion: A Feasibility Study

Abstract

Abstract-Spread tumors in liver are not suitable to be treated with local treatments, such as conventional surgery or radiofrequency ablation, thus entailing a poor prognosis. Electroporation-based therapies imply the delivery of pulsed high electric fields and currently are performed in a local fashion using needle or plate electrodes. Here, however, it is proposed a novel electroporation paradigm in which field delivery is not local. All the tumor nodules will be selectively treated using large plate electrodes at both sides of the liver. By infusing an hypersaline solution of high electrical conductivity through the portal vein, the electrical conductivity of healthy tissues and tumor nodules will be made significantly different so that the electric field will be focused on the undesirable tissues. Numerical simulations were used to evaluate the feasibility of the proposed technique. In addition, an in vivo procedure was carried out to assess whether it is possible and practical to significantly modify the conductivity of the liver tissue by hypersaline infusion. Both the numerical simulations and the in vivo procedure provided encouraging results.

Modeling liver electrical conductivity during hypertonic injection

“…In view of the foregoing, we propose to inject a hypertonic saline solution (HS) with high electrical conductivity through the portal vein so that the overall conductivity of the healthy tissue increases whereas the conductivity in the tumor nodules is kept constant. Then, by applying high voltage pulses across 2 large electrode plates sandwiching the liver, a significantly larger field would be caused in the tumors than in the rest of the tissue, as described in the previous theoretical study . In this way, it would be possible to cause electroporation of the tumor nodules while avoiding the effect in healthy parenchyma.…”

“…These techniques, however, because of their focal nature, are not adequate for patients in which the number of scattered nodules is large (>3) . As an alternative, we have recently proposed a technique based on irreversible electroporation (IRE) that may be able to simultaneously treat all nodules in the liver while sparing healthy liver tissue …”

“…Prior to further development of the proposed technique, it is required to assess the capability to increase the electrical conductivity of the liver. We deem that the proposed liver electroporation technique will require increasing healthy liver conductivity by a minimum factor of 3. Here, to elucidate the expected behavior of conductivity during the procedure, a comprehensive mathematical model has been developed to predict both the temporal distribution of solute within the liver and the resulting electrical conductivity of the tissue.…”

Focused transhepatic electroporation mediated by hypersaline infusion through the portal vein in rat model. Preliminary results on differential conductivity

“… 17 Interestingly, the tumour nodules lack of sinusoids means they are only supplied with blood from the hepatic artery. 18 , 19 , 20 In fact, this characteristic is currently used for identifying tumours by injecting contrast agents with CT or MRI. Hypersaline infusion through the portal vein would therefore raise the electrical conductivity of the healthy hepatic tissue, so that, when a potential difference is applied between the opposite sides of the liver, the electrical field magnitude in the tumours would be significantly larger than in the rest of the healthy tissue.…”

Irreversible electroporation of the liver: is there a safe limit to the ablation volume?

“…Our group has been working on a novel IRE approach carried out in an immunosuppressed murine model of liver metastases in which the IRE ablation volume was unusually large 16 : we delivered pulses across two parallel plates that comprise two segments of the left liver which corresponds to nearly 40% of its volume 17 18 . Unlike thermal ablation techniques, IRE preserves the extracellular matrix and this may allow novel treatment paradigms.…”