Transcatheter intra‐arterial perfusion (TRIP)‐MRI biomarkers help detect immediate response to irreversible electroporation of rabbit VX2 liver tumor

Abstract

Purpose Irreversible electroporation (IRE) is a nonthermal tissue ablation technique that represents a promising treatment option for unresectable liver tumors, but the effectively treated zone cannot be reliably predicted. We investigate the potential benefit of transcatheter intra‐arterial perfusion (TRIP) ‐MRI for the early noninvasive differentiation of IRE zone from surrounding reversibly electroporated (RE) zone. Methods Seventeen rabbits with VX2 liver tumors were scanned with morphological and contrast‐enhanced MRI sequences approximately 30 min after IRE tumor ablation. Quantitative TRIP‐MRI perfusion parameters were evaluated in IRE zone and RE zone, defined according to histology. MRI and histology results were compared among zones using Wilcoxon rank‐sum tests and correlations were evaluated by Pearson’s correlation coefficient. Results There were significant differences in area under the curve, time to peak, maximum and late enhancement, wash‐in and wash‐out rates in the tumor IRE zones compared with the boundary tumor RE zones and untreated tumors. Histology showed significantly fewer tumor cells, microvessels and significantly more apoptosis in tumor IRE zones compared with tumor RE zones (−51%, −66% and +185%, respectively) and untreated tumors (−60%, −67%, and +228%, respectively). A strong correlation was observed between MRI and histology measurements of IRE zones (r = 0.948) and RE zones (r = 0.951). Conclusion TRIP‐MRI demonstrated the potential to detect immediate perfusion changes following IRE liver tumor ablation and effectively differentiate the IRE zone from the surrounding tumor RE zone.

Combination of natural killer cell-based immunotherapy and irreversible electroporation for the treatment of hepatocellular carcinoma

“…In another experiment, potential clinical translation of the IRE ablation method was investigated using VX2 liver tumor model with single or multiple ablations on twenty New Zealand white rabbits (80). Several studies focused on immediate therapeutic response following IRE in animal models (78,(81)(82)(83)(84)(85)(86)(87) (86,87). The results further emphasize the potential of immediate evaluation of RE regions using MRI to determine the treatment strategy (Figure 4).…”

Rabbit VX2 Liver Tumor Model: A Review of Clinical, Biology, Histology, and Tumor Microenvironment Characteristics

“…Dynamic contrast-enhanced MRI (DCE-MRI) measures several parameters to quantitatively assess tissue vessel density, integrity, and permeability ( 48 , 49 ) and further allows the visualization of hypoxic areas of the tumors ( 50 ). Transcatheter intra-arterial perfusion (TRIP) MRI was developed as an arterial analog to DCE-MRI to help quantify hepatic arterial perfusion in tumors ( 51 ).…”

<p>Intraprocedural Transcatheter Intraarterial Perfusion (TRIP)-MRI for Evaluation of Irreversible Electroporation Therapy Response in a Rabbit Liver Tumor Model</p>

“…6 IRE causes two ablation zones: central IRE zone with permanent nanopores and complete cell death and peripheral reversible electroporation (RE) zone with transient nanopores and mostly cell swelling. 7 IRE technique demonstrated promising results in earlystage HCC, lacked heat sink effects, and preserved healthy adjacent tissues. [8][9][10] Additionally, IRE generates clear treatment margins that can be identified by imaging.…”

“…15 However, functional changes in tissue perfusion after IRE treatment have not been studied. 7,16,17 Transcatheter intraarterial perfusion (TRIP)-MRI is a wellestablished technique for functional evaluation of tissue perfusion changes by injecting small doses of contrast to supplying blood vessels. 18,19 Liver tissue perfusion changes have been evaluated before by traditional intravenous methods, but TRIP-MRI allows continuous iterative imaging at higher spatial and temporal resolutions than conventional perfusion MRI using IV contrast injection.…”

“…19 TRIP-MRI has also been previously used to evaluate liver perfusion changes after other locoregional approaches. 7 In this project, we aimed to study normal liver and liver tumor perfusion changes immediately after IRE ablation using intraprocedural TRIP-MRI and investigate intraprocedural TRIP-MRI as a potential method to monitor of treatment zone margins immediately after IRE procedure.…”