A characterization of the reversibly electroporated penumbra during irreversible electroporation

Background: Irreversible electroporation (IRE) is a novel anticancer ablative treatment, which has been proposed to enhance the efficacy of chemotherapy in the periphery of the ablated area by capturing chemotherapy intracellularly. The aim of the current trial was to characterize the ablated lesion to get spatial information about the distribution of captured chemotherapy and in extension to assess the a priori probability of efficacy for the combined intervention. Methods: IRE ablations were performed in five pigs with or without concurrent intravenous bleomycin and gadolinium contrast injection. Magnetic resonance (MR) scans were performed to examine the distribution of contrast in the ablated areas and images were segmented to quantify the volumes of the ablations. Pig plasma and tissues were analyzed for bleomycin using quantitative liquid chromatography mass spectrometry. Results: MR images showed a hypointense inner surrounded by a hyperintense outer penumbra effectively doubling the volume of the ablated lesion, when gadolinium contrast and bleomycin were given just prior to IRE. In contrast, the ablations without prior contrast and bleomycin only produced a small or no hyperintense area. Bleomycin was not detectable in any of the examined tissue samples. Conclusions: A contrast enhancing penumbra can be visualized using clinically available MRI aligning with theoretical models. Regions of transient permeability may expand the apparent margins after IRE. However, this study does not provide direct evidence of intracellular bleomycin entrapment and thus results should be interpreted with caution.