An evaluation of irreversible electroporation thresholds in human prostate cancer and potential correlations to physiological measurements

Abstract

Irreversible electroporation (IRE) is an emerging cancer treatment that utilizes non-thermal electric pulses for tumor ablation. The pulses are delivered through minimally invasive needle electrodes inserted into the target tissue and lead to cell death through the creation of nanoscale membrane defects. IRE has been shown to be safe and effective when performed on tumors in the brain, liver, kidneys, pancreas, and prostate that are located near critical blood vessels and nerves. Accurate treatment planning and prediction of the ablation volume require a priori knowledge of the tissue-specific electric field threshold for cell death. This study addresses the challenge of defining an electric field threshold for human prostate cancer tissue. Three-dimensional reconstructions of the ablation volumes were created from one week post-treatment magnetic resonance imaging (MRIs) of ten patients who completed a clinical trial. The ablation volumes were incorporated into a finite element modeling software that was used to simulate patient-specific treatments, and the electric field threshold was calculated by matching the ablation volume to the field contour encompassing the equivalent volume. Solutions were obtained for static tissue electrical properties and dynamic properties that accounted for electroporation. According to the dynamic model, the electric field threshold was 506 ± 66 V/cm. Additionally, a potentially strong correlation ( r = −0.624) was discovered between the electric field threshold and pre-treatment prostate-specific antigen levels, which needs to be validated in higher enrollment studies. Taken together, these findings can be used to guide the development of future IRE protocols.

Numerical workflow of irreversible electroporation for deep-seated tumor

“…The isolines 650 V.cm −1 and 300 V.cm −1 are the theoretical threshold EF magnitudes needed for irreversible reversible electroporation, however since the total number of pulses at the end of the procedure is high (200 pulses are delivered), the irreversible magnitude might be lower. For instance Campelo et al found that a electric field magnitude of 500 V.cm −1 could be sufficient for clinical IRE of prostate tumors [2]. Figure 7(b) shows the isolines 650, 500 and 300 V.cm −1 registered on the CBCT.…”

“…IRENA: a C++ finite difference method based software for IRE numerical assessment. Model (2) has been implemented in the C++ software IRENA [11] developed by O. Gallinato and C. Poignard within the Inria team Monc. The code is based on the finite difference method on Cartesian grid [9].…”

“…The detailed procedure to obtain accurately the numerical intensity is given in [11]. It is therefore possible to fit the numerical intensities on the recorded intensities to obtain the parameters σ 0 and a ep of model (2) for each region of interest (liver, tumor, scar...). We use here a simple trial and error method.…”

“…To assess the treatment success, an MRI is performed a few 1 There is still a huge uncertainty on the EF magnitude threshold and on the number of micropulses needed to generate cell apoptosis, but it is commonly accepted that EF of magnitude above 500V/cm for several tens of 100µs pulses leads to cell death. 2 There is currently only one device for clinical IRE: Nanoknife R developed by Angiodynamics, Latham, NY. 2 days after the treatment (2 to 3 days), but the interpretation of the posttreatment images is still controversial [39].…”

“…2 There is currently only one device for clinical IRE: Nanoknife R developed by Angiodynamics, Latham, NY. 2 days after the treatment (2 to 3 days), but the interpretation of the posttreatment images is still controversial [39].…”