Irreversible Electroporation Therapy in the Liver: Longitudinal Efficacy Studies in a Rat Model of Hepatocellular Carcinoma

Abstract

Irreversible electroporation (IRE) is an innovative local-regional therapy that involves delivery of intense electrical pulses to tissue to induce nanoscale cell membrane defects for tissue ablation. The purpose of this study was to investigate the feasibility of using IRE as a liver-directed ablation technique for the treatment of hepatocellular carcinoma (HCC). In the N1-S1 rodent model, hepatomas were grown in 30 Sprague-Dawley rats that were divided into treatment and control groups. For treatment groups, IRE electrodes were inserted and eight 100-μs 2,500-V pulses were applied to ablate the targeted tumor tissues. For both groups, magnetic resonance imaging scans were performed at baseline and 15-day follow-up intervals to determine tumor sizes (one-dimensional maximum diameter, D max ; estimated two-dimensional cross-sectional area, C max ) as a tactic to assess longitudinal outcomes. Additional groups of treated animals were sacrificed at 1-, 3-, and 7-day intervals posttherapy for pathology assessment of treatment response. Magnetic resonance images showed significant tumor size reductions within 15 days posttherapy (32 ± 31% D max and 52 ± 39% C max decreases compared with 110 ± 35% D max and 286 ± 125% C max increases for untreated tumors). Pathology correlation studies documented progression from poorly differentiated viable HCC tissues before treatment to extensive tumor necrosis and full regression in 9 of 10 treated rats 7 to 15 days after treatment. Our findings suggest that IRE can be an effective strategy for targeted ablation of liver tumors, prompting its further evaluation for HCC therapy.

Chemical Shift MR Imaging Methods for the Quantification of Transcatheter Lipiodol Delivery to the Liver: Preclinical Feasibility Studies in a Rodent Model

“…The portal vein was chosen given its larger diameter and surgical accessibility. Given the promising outcomes of these initial feasibility studies, future investigations are now warranted to evaluate the efficacy of these methods for the quantification of lipiodol delivery to liver tumors (39); such investigations should also compare the proposed MR imaging-based lipiodol distribution measurements to longitudinal outcomes, but this was beyond the scope of the current validation study. Finally, ex vivo imaging permitted long repetition times with a relatively high flip angle (75°) for superior signal-to-noise ratio; gating procedures and appropriately optimized sequence parameters will be necessary to avoid respiratory motion artifacts and potential T1 bias (31,40,41) during future in vivo imaging studies.…”

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

“…Co.) as previously described. 31 All scans were performed with a 150 mm field-of-view, 2.0 mm slice thickness, repetition and echo time (TR/TE) ¼ 4,980/112 ms 32 measurements were performed offline on axial T2-weighted images between the L4 and L5 transverse processes. Regions of interest (ROI) measuring 4 Â 4 mm 2 were then drawn just superior and superficial to the L5 transverse process on each scan.…”

Electroporation: characteristics and therapeutic application of the method (a review)

“…На основании проведенного ана-лиза данных ультразвукового, клинико-лабораторного и па-тогистологического исследований доказана высокая эффек-тивность метода, а также безопасность его для сосудистых и протоковых структур печени [32]. Другими авторами в экс-периментах на свиньях и крысах также показано, что необ-ратимая электропорация вызывает абляцию тканей, не по-вреждая стенки крупных сосудов и эндотелий [33,34].…”